3月1日
Cancer Services And Research Spending Affected By Global
Recession
According to several interconnected reports published in the March issue of The Lancet
Oncology, in Europe and in the UK, governments´, companies', and individuals´ budgets are
affected by the global financial crisis. This could result in the future in reduced access to costly
cancer treatments, lower investment in drug research and declining support for cancer
sufferers and survivors.
The irregular provision of screening programmes and uneven spending on cancer care imply
that the effects of the economic crisis will be more intense in some areas, according to the
reports.
Across Europe, inequalities in access to cancer services as well as new drugs are outlined in
the first of the two Special Reports published in The Lancet Oncology.
Nils Wilking, Karolinska Institute, Sweden, co-author of the Comparator Report on Patient
Access to Cancer Drugs in Europe, remarks: "Per capita spending on drugs (new as well as
pre-1999) is significantly lower in the UK compared with France and almost all other western
European countries".
As the economic crisis intensifies, it seems this spending will decrease even more. In a
comment in the second Special Report, Nick Bosanquet, Imperial College, London, UK says:
"In Europe there are likely to be informal steps towards rationing access to new treatments as
governments seek to contain spending; we are already seeing this in the UK through the
restrictions placed on the uptake of expensive drugs by the National Institute for Health and
Clinical Excellence (NICE)." Furthermore, Alan Maynard, University of York, UK, highlights: the
UK Institute of Fiscal Studies calculates NHS funding may be equal to zero real growth for the
3 years following 2010. Considering the rest of Europe, Maynard also points out: "In Europe
some will fare better but some will fare worse, notably Ireland and the Baltic republics."
With increasing unemployment and declining sales and profits, donations by companies and
private individuals are likely to diminish. Cancer aid programmes and research that depend on
charitable financial support are expected to deteriorate. A fall of 4 to 5 percent in income in
2009 compared with 2008 is predicted by Cancer Research UK. Macmillan Cancer Support,
forecasts that the economic crisis will particularly affect cancer patients depending on their
financial aid.
As budgets squeeze, there is greater need for competent administration and equal supply of
cancer services. However, this seems very remote due to the present inequalities and misuse,
as pointed out by The Lancet Oncology, in this month´s editorial, the Leading Edge.
Observing on the expanding disparities in access to cancer treatment across the UK, The
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Lancet Oncology says: "This makes a mockery of the concept of a 'National' Health Service,
when the four countries within the UK each have different interpretations…In the current global
recession, a root and branch re-evaluation of services, focused on patient-centred
medicine…would undoubtedly improve care for patients with cancer; reduce polarisation in
accessibility; and possibly even shrink healthcare budgets".
3月2日
Brain Tumor Research Center A Lasting Legacy At Barrow
William Shapiro, MD, and Joan Rankin Shapiro, PhD, have collaborated for 20 years to help
build a world-renowned brain tumor research center at Barrow Neurological Institute at St.
Joseph's Hospital and Medical Center. After years of dedicated patient care and research, the
Shapiros have established a $1.5 million endowed chair dedicated to neuro-oncology research.
"The endowed chair represents our desire to give back and will allow Barrow to hire the best
and the brightest to carry on research in brain tumors," says Bill. "We want Barrow to
succeed."
The Shapiro's endowed chair enables nationally recognized physicians and scientists to
pursue research and run laboratories, ensuring long-term viability and success of
neuro-oncology research. A minimum of $1.5 million was required to create their endowed
chair and the investment will be used for expenses such as salaries for post-doctoral
candidates, fellows and research assistants; and research equipment.
In their two decades at St. Joseph's, the Shapiros have also remained devoted to giving back
by fostering the next generation of scientists at Barrow. Bill established a neuro-oncology
fellowship program in which he trains neuro-oncologists. Joan established the scientific
enrichment program for students. The program allows high school, college and medical
students to work in the Neuro-Oncology Lab at Barrow.
"It's a payback system and it's rewarding to get the students involved," says Joan. "We've both
impacted the experimental field and patient community," Bill adds.
In November 2007, the Shapiros received a lifetime achievement award from the Society for
Neuro-Oncology, the second such award given by the organization. The award recognized the
Shapiros as pioneers in neuro-oncology who have contributed significantly to the
understanding and management of brain tumors.
Though they have held many executive level positions at Barrow, Bill is currently serving as
the interim chair of Neurology and Joan is the vice president of Clinical Research. They spend
countless hours studying brain tumors and finding effective treatments for the disease -a
cause that is not easy for either of them to walk away from.
"We're naturally recognized as a team and that is a good thing," says Joan. "We have always
been supportive of each other. We offer the medical and scientific community a unique set of
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experiences."
---------------------------Article adapted by Medical News Today from original press release.
---------------------------Source: Andrea Bailey
3月3日
Clinical Study Evaluates MORAb-009 Plus Standard Of Care For
Extending Survival Of Patients With Mesothelioma
Morphotek®, Inc., a subsidiary of Eisai Corporation of North America, has announced that it has
commenced a multi-centered Phase II study of its MORAb-009 monoclonal antibody in
mesothelioma. The study will evaluate MORAb-009, plus the chemotherapy drugs pemetrexed
and cisplatinum, as a first-line treatment for patients with mesothelioma.
The primary objective of the study is to assess the efficacy of MORAb-009 as combination
therapy with the current standard of care as determined by progression-free survival in patients
with locally advanced malignant pleural mesothelioma. Secondary objectives include safety and
anti-tumor activity of MORAb-009 as determined by objective response rate. The patient
population includes individuals with locally advanced malignant pleural mesothelioma who have
not received any prior treatment for their disease. Morphotek expects to enroll up to 86 patients in
this clinical study, which is being conducted at clinical centers globally.
"We are excited to have initiated this Phase II study of MORAb-009 in mesothelioma in
cooperation with leading physician-scientists," stated Martin D. Phillips, M.D., Chief Medical
Officer at Morphotek. "Mesothelioma has a generally poor prognosis, so we hope that
MORAb-009 will one day provide a benefit and hope to mesothelioma cancer patients."
MORAb-009 is a monoclonal antibody that blocks the function of mesothelin, a cell surface
protein on mesothelioma, pancreatic and a subset of other types of tumor cells that can allow these
cells to attach, metastasize and grow. Mesothelin has been demonstrated by several independent
studies to be expressed on virtually all mesothelioma tumors. Preclinical data support the theory
that MORAb-009 achieves its pharmacological effect by two mechanisms: first, by blocking
mesothelin's ability to interact with its target and second, by stimulating the patient's immune
system to attack the tumor by specifically destroying those cells bound by MORAb-009. The
Phase II clinical trial is supported by safety data and clinical observations from a recently
completed Phase I trial of MORAb-009 in patients with mesothelin-bearing tumors, including
pancreatic, mesothelioma and ovarian cancers as well as data derived from preclinical models.
Mesothelioma develops in the chest outside the lungs, usually growing asymptomatically before it
is discovered. It is especially common in people who have been exposed to asbestos, such as ship
yard workers and pipefitters. Each year, an estimated 2,500 to 3,000 people are diagnosed with
3
mesothelioma in the United States. It accounts for more than 2,500 deaths in the United States. It
accounts for approximately 43,000 deaths worldwide each year.
Notes:
About Morphotek
Morphotek, Inc., a subsidiary of Eisai Corporation of North America, is a biopharmaceutical
company specializing in the development of protein and antibody products through the use of a
novel and proprietary gene evolution technology. The technology has been successfully applied to
a broad variety of cell lines and organisms to yield genetically diverse offspring that are suitable
for pharmaceutical product development in the areas of antibody therapeutics, protein therapeutics,
product manufacturing, drug target discovery, and improved output traits for commercial
applications. The company is currently focusing its platform on the development and
manufacturing of therapeutic antibodies for the treatment of cancer, inflammation and infectious
disease. For more information, please visit http://www.morphotek.com/.
About Eisai Corporation of North America
Eisai Corporation of North America is a wholly-owned subsidiary of Eisai Co., Ltd., a
research-based human health care (hhc) company that discovers, develops and markets products
throughout the world. Eisai focuses its efforts in three therapeutic areas: neurology,
gastrointestinal disorders and oncology/critical care. Eisai Corporation of North America supports
the activities of its operating companies in North America, which include: Eisai Research Institute
of Boston, Inc., a discovery operation with strong organic chemistry capabilities; Morphotek, Inc.,
a biopharmaceutical company specializing in the development of therapeutic monoclonal
antibodies; Eisai Medical Research Inc., a clinical development group; Eisai Inc., a commercial
operation with manufacturing and marketing/sales functions; and Eisai Machinery U.S.A., which
markets and maintains pharmaceutical manufacturing machinery. For more information about
Eisai, please visit http://www.eisai.com/.
3月3日
Morphotek(R), Inc. Announces Initiation Of MORAb-009 Phase II
Study In First- Line Treatment Of Mesothelioma
Morphotek(R), Inc., a subsidiary of Eisai Corporation of North America, announced that it has
commenced a multi-centered Phase II study of its MORAb-009 monoclonal antibody in
mesothelioma. The study will evaluate MORAb-009, plus the chemotherapy drugs pemetrexed
and cisplatinum, as a first-line treatment for patients with mesothelioma.
The primary objective of the study is to assess the efficacy of MORAb-009 as combination
therapy with the current standard of care as determined by progression-free survival in
patients with locally advanced malignant pleural mesothelioma. Secondary objectives include
safety and anti-tumor activity of MORAb-009 as determined by objective response rate. The
4
patient population includes individuals with locally advanced malignant pleural mesothelioma
who have not received any prior treatment for their disease. Morphotek expects to enroll up to
86 patients in this clinical study, which is being conducted at clinical centers globally.
"We are excited to have initiated this Phase II study of MORAb-009 in mesothelioma in
cooperation with leading physician-scientists," stated Martin D. Phillips, M.D., Chief Medical
Officer at Morphotek. "Mesothelioma has a generally poor prognosis, so we hope that
MORAb-009 will one day provide a benefit and hope to mesothelioma cancer patients."
MORAb-009 is a monoclonal antibody that blocks the function of mesothelin, a cell surface
protein on mesothelioma, pancreatic and a subset of other types of tumor cells that can allow
these cells to attach, metastasize and grow. Mesothelin has been demonstrated by several
independent studies to be expressed on virtually all mesothelioma tumors. Preclinical data
support the theory that MORAb-009 achieves its pharmacological effect by two mechanisms:
first, by blocking mesothelin's ability to interact with its target and second, by stimulating the
patient's immune system to attack the tumor by specifically destroying those cells bound by
MORAb-009. The Phase II clinical trial is supported by safety data and clinical observations
from a recently completed Phase I trial of MORAb-009 in patients with mesothelin-bearing
tumors, including pancreatic, mesothelioma and ovarian cancers as well as data derived from
preclinical models.
Mesothelioma develops in the chest outside the lungs, usually growing asymptomatically
before it is discovered. It is especially common in people who have been exposed to asbestos,
such as ship yard workers and pipefitters. Each year, an estimated 2,500 to 3,000 people are
diagnosed with mesothelioma in the United States and it accounts for more than 2,500 deaths
in the United States. It accounts for approximately 43,000 deaths worldwide each year.
About Morphotek
Morphotek, Inc., a subsidiary of Eisai Corporation of North America, is a biopharmaceutical
company specializing in the development of protein and antibody products through the use of
a novel and proprietary gene evolution technology. The technology has been successfully
applied to a broad variety of cell lines and organisms to yield genetically diverse offspring that
are suitable for pharmaceutical product development in the areas of antibody therapeutics,
protein therapeutics, product manufacturing, drug target discovery, and improved output traits
for commercial applications. The company is currently focusing its platform on the
development and manufacturing of therapeutic antibodies for the treatment of cancer,
inflammation and infectious disease. For more information, please visit
http://www.morphotek.com.
About Eisai Corporation of North America
Eisai Corporation of North America is a wholly-owned subsidiary of Eisai Co., Ltd., a
research-based human health care (hhc) company that discovers, develops and markets
5
products throughout the world. Eisai focuses its efforts in three therapeutic areas: neurology,
gastrointestinal disorders and oncology/critical care. Eisai Corporation of North America
supports the activities of its operating companies in North America, which include: Eisai
Research Institute of Boston, Inc., a discovery operation with strong organic chemistry
capabilities; Morphotek, Inc., a biopharmaceutical company specializing in the development of
therapeutic monoclonal antibodies; Eisai Medical Research Inc., a clinical development group;
Eisai Inc., a commercial operation with manufacturing and marketing/sales functions; and
Eisai Machinery U.S.A., which markets and maintains pharmaceutical manufacturing
machinery. For more information about Eisai, please visit http://www.eisai.com.
3月4日
MRI and PET/CT Improve Chances for Optimal Treatment and Minimal
Complications in Cervical Cancer Patients
Pretreatment MRI and PET/CT for cervical cancer may direct more women to optimal therapy
choices and spare many women potential long-term morbidity and complications of
trimodality therapy (surgery followed by chemoradiation), according to a study performed at
the Institute for Technology Assessment in Boston, MA.
An interdisciplinary team of investigators developed a decision-analytic model to determine
the value of pretreatment imaging with MRI and/or PET/CT in patients with FIGO Stage IB
cervical cancer. “Stage IB cervical cancer, in the absence of pre-treatment imaging, is treated
with surgery. As surgery cannot completely resect the cancer in many of these patients, they
receive post-surgical chemoradiation, i.e. trimodality therapy,” said Pari Pandharipande, MD,
lead author of the study. “The goal of pre-treatment imaging is to identify these patients
noninvasively, spare them surgery and have them treated with chemoradiation alone,” she
said. Study results showed that while imaging does not improve survival, PET/CT resulted in
the highest percentage of patients receiving correct primary therapy (89%) and use of both
MRI and PET/CT spared the most patients of trimodality therapy (95%).
“Pretreatment imaging can triage patients to optimal primary treatment choices that
minimize the risk of long-term complications and morbidity while preserving chances for
survival,” said Dr. Pandharipande. “Because both over- and underestimation of disease
extent can result in adverse patient outcomes, determining the extent of disease accurately
up front is critical. For example, when patients are subjected to pelvic surgery, and then are
radiated in the same operative field, complication rates can increase by a substantial
percentage, as compared to if they were simply treated with surgery alone or chemoradiation
alone. Our study shows how pre-treatment imaging may improve chances of correctly
receiving surgery or chemoradiation instead of both,” said Dr. Pandharipande.
“MRI and PET/CT are expensive, but long-term consequences of trimodality therapy can
severely affect long-term quality of life and are also expensive. Further study of these
long-term consequences is needed to more precisely consider the cost implications of upfront
MRI and PET/CT,” she said.
6
“Currently there are no specific guidelines that prescribe MRI or PET/CT for determining a
plan of action for the treatment of stage IB cervical cancer patients. It remains important for
patients to make imaging and treatment decisions with their gynecologic-oncologist on a
case-by-case basis,” said Dr. Pandharipande.
“My goal as a researcher in radiology is to continue to objectively look at what we do and how
it impacts patient care. A better understanding of what happens to people after they receive
imaging tests both improves patient care directly and focuses further research efforts in
areas most influential to patient outcomes,” she said.
This study appears in the March issue of the American Journal of Roentgenology. For a copy
of the full study, please contact Heather Curry via email at hcurry@arrs.org.
Click here for abstract
About ARRS
The American Roentgen Ray Society (ARRS) was founded in 1900 and is the oldest radiology
society in the United States. Its monthly journal, the American Journal of Roentgenology,
began publication in 1906. Radiologists from all over the world attend the ARRS annual
meeting to participate in instructional courses, scientific paper presentations and scientific
and commercial exhibits related to the field of radiology. The Society is named after the first
Nobel Laureate in Physics, Wilhelm Röentgen, who discovered the x-ray in 1895. ###
3月4日
New Innovations To Selectively Kill Cancer Cells Developed By MIT Student
When it comes to solving complex problems, Geoffrey von Maltzahn, MIT graduate student
and biomedical engineer, looks to nature for solutions. Finding inspiration in systems that
evolution has produced, von Maltzahn is currently helping to tackle one of society's biggest
challenges: improving tumor detection and therapeutic delivery in order to boost the survival
rate of cancer patients.
The 28-year-old Ph.D. candidate in the Harvard-MIT Division of Health Sciences and
Technology (HST) received the prestigious $30,000 Lemelson-MIT Student Prize for his
promising innovations in the area of cancer therapy, specifically two inventions in
nanomedicine: a new class of cancer therapeutics and a new paradigm for enhancing drug
delivery to tumors.
Cancer currently kills more people worldwide than HIV/AIDS, tuberculosis and malaria
combined. Despite billions of dollars invested into drug development and decades of research,
selectively eradicating cancer cells has remained an elusive goal. Chemotherapies, a common
class of cancer treatments, are intended to kill the fast-growing cells that form tumors.
However, these drugs travel throughout the entire body, and often affect normal, healthy tissue
7
along with cancer cells, causing side effects such as hair loss, nausea, anemia, and even
nerve and muscle problems. Furthermore, resistance to these drugs can arise and can cause
even initially successful treatment regimens to fail.
Working at the confluence of nanotechnology, engineering and medicine, von Maltzahn's
innovations have the potential to reduce side effects and overpower drug resistance
mechanisms by more powerfully concentrating external energy and targeted therapeutics in
tumors.
Using Gold Nano-Antennas to Target and Destroy Tumors
Since 2004, von Maltzahn has worked closely with his advisor, Dr. Sangeeta N. Bhatia, an
electrical engineering and computer science professor in the Harvard-MIT Division of HST, to
invent novel treatments that could precisely target and destroy tumor cells without affecting
healthy tissue. Seeking to improve the specificity of cancer ablation - the destruction of tumors
through the application of heat - von Maltzahn developed polymer-coated gold
'nano-antennas' that can target tumors and convert benign-infrared light into heat.
The nanoparticles are designed to be injected intravenously, where they circulate through the
bloodstream and progressively concentrate at the tumor site by infiltrating pores in rapidly
growing tumor blood vessels. Once in the tumor, the antennas can be precisely heated with a
non-invasive, near-infrared light to specifically kill the cancerous cells. "The polymer coated
gold nano-antennas are the longest-circulating and most efficiently heated to date," states Dr.
Bhatia. "Pre-clinical trials reveal that a single intravenous nanoparticle injection eradicated 100
percent of tumors in mice using a near-infrared light. The results of these trials are very
promising, meaning that the impact of this technology is wide-reaching with many potential
applications."
Scout and Assassin: Communicating Nanoparticles
Von Maltzahn's second invention aims to fundamentally improve the intravenous delivery of
therapeutics to tumors by taking a 'systems' approach to their design. This work draws on
insights from biological systems, like ants foraging and bees swarming, where relatively simple
methods of communication can lead to very sophisticated system behaviors.
Inspired by the potential for inter-nanoparticle communication to improve therapeutics' ability
to find tumors, von Maltzahn invented a series of ways for nanoparticles to 'talk' to one another
in the body. One method involves benign 'scout' particles initially locating the tumor and, once
inside, sending powerful signals to recruit secondary, 'assassin' particles that contain the
therapeutics. In pre-clinical trials, this system has been able to deliver over 40-times higher
doses of therapeutics to tumors in mice, in comparison to non-communicating control
nanoparticles.
"If such highly-targeted delivery can be achieved clinically, this method would enable doctors
8
to increase the drug dose that is delivered to tumors, increasing its overall efficacy and
reducing side-effects," von Maltzahn explains. "This concept of engineering systems of
nanoparticles that collectively outsmart disease barriers has many potential applications in
medicine, from improving regenerative medicines to ultra-sensitive diagnostics."
Looking Forward
Von Maltzahn's work has already made a significant impact scientifically and commercially,
resulting in eight patent applications, 19 submitted or published papers, and his founding roles
in two companies: Nanopartz Inc. and Resonance Therapeutics.
Nanopartz was founded more than one year ago to address the nanotechnology industry's
need for dependable and standardized nanoparticle sources. Von Maltzahn's goal with
Nanopartz is to aid in research endeavors worldwide by supplying a repertoire of gold
nanoparticles for a broad spectrum of commercial applications, ranging from biomedicine to
energy.
Resonance Therapeutics was founded to bring nano-rods towards clinical applications and to
develop technologies that amplify the efficacy of existing cancer therapeutics.
"In addition to the long hours spent in the lab, finishing up his Ph.D., and founding two
companies, Geoff mentored 14 undergraduate students, taking them out of the classroom
setting and inspiring them to make the link from science to the real world," states Joshua
Schuler, the executive director of the Lemelson-MIT Program. "Geoff is not only a mentor for
aspiring scientists, but also a shining example of bridging the gap between technological
invention and entrepreneurship."
Additional Inventions
During von Maltzahn's time at MIT he has also developed inventions outside of the polymer
nano-rods and 'systems nanotechnology' paradigm for improving drug delivery, including: a
low-cost method for hemorrhage detection; a new class of 'self-assembling' lipid-like peptides
with promising applications in gene therapy; sensors for detecting tumor protease hot-spots in
MRI; a method for remotely-controlling drug release from nanoparticles; and a variety of new
nanostructures for improved drug delivery and imaging.
Collegiate Student Prize Expansion
On March 4th, the winners of the third annual $30,000 Lemelson-Illinois Student Prize and
$30,000 Lemelson-Rensselaer Student Prize will be announced at the University of Illinois at
Urbana-Champaign and Rensselaer Polytechnic Institute, respectively. Following, on March
5th the first $30,000 Lemelson-Caltech Student Prize will be announced at the California
Institute of Technology.
9
Notes:
ABOUT THE $30,000 LEMELSON-MIT STUDENT PRIZE
The $30,000 Lemelson-MIT Student Prize is awarded annually to an MIT senior or graduate
student who has created or improved a product or process, applied a technology in a new way,
redesigned a system, or demonstrated remarkable inventiveness in other ways. A
distinguished panel of MIT alumni including scientists, technologists, engineers and
entrepreneurs chooses the winner.
ABOUT THE LEMELSON-MIT PROGRAM
The Lemelson-MIT Program recognizes outstanding inventors, encourages sustainable new
solutions to real-world problems, and enables and inspires young people to pursue creative
lives and careers through invention.
Jerome H. Lemelson, one of U.S. history's most prolific inventors, and his wife Dorothy
founded the Lemelson-MIT Program at the Massachusetts Institute of Technology in 1994. It is
funded by the Lemelson Foundation, a philanthropy that celebrates and supports inventors
and entrepreneurs in order to strengthen social and economic life in the U.S. and developing
countries. More information on the Lemelson-MIT Program is online at
http://web.mit.edu/invent/.
Source: Julie Staadecker
3月4日
ARIAD Announces Start Of Phase 2 Clinical Study Of Oral Deforolimus In Patients
With Advanced Non-Small Cell Lung Cancer
ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) announced the initiation by Merck & Co. Inc.,
of a Phase 2 clinical trial to evaluate the safety and efficacy of oral deforolimus, ARIAD's
investigational mTOR inhibitor, in patients with advanced non-small cell lung cancer.
Deforolimus is currently being studied in multiple clinical trials, both alone and in combination
with other therapies, in patients with several different types of cancer. Under the terms of the
agreement, ARIAD will receive a $10 million milestone payment from Merck upon treatment of
the first patient in this clinical study.
The multi-center, randomized, double-blind, placebo controlled clinical trial will compare oral
deforolimus against placebo in patients with advanced non-small cell lung cancer whose
tumors have a KRAS mutation. The presence of KRAS mutations in lung tumors is a
recognized predictor of poor response to EGFR inhibitors such as erlotinib.
The trial utilizes a randomized discontinuation design in which all patients initially receive
deforolimus. Those patients who respond to treatment will continue on therapy, while those
whose disease is stable will be randomized to continued oral deforolimus or placebo.
Supportive care elements for patients are the same in the two arms of the study after
10
randomization. This trial is designed to assess control of disease progression by oral
deforolimus. The primary endpoint of the study is progression-free survival in the randomized
population.
The clinical trial will enroll approximately 150 patients who have failed two prior treatment
regimens. It will be conducted at approximately 38 sites including medical centers in the United
States and abroad.
"There is a significant unmet medical need for the treatment of patients with advanced
non-small cell lung cancer who have KRAS positive tumors and are refractory to currently
available therapies," stated Pierre F. Dodion, M.D., senior vice president and chief medical
officer of ARIAD. "The design of this clinical trial is supported by preclinical data on deforolimus
that will be presented at the upcoming American Association for Cancer Research meeting this
spring and advocates evaluating deforolimus further in this patient population."
This is the fourth Phase 2 clinical trial of oral deforolimus conducted by ARIAD and Merck to
begin within the past year.
For more information about clinical trials evaluating deforolimus, or to find a trial site close to
you, patients and physicians should call the US toll-free number 1-877-621-2302 or the
international number 1-617-621-2302, or email us at ClinicalTrials@ariad.com. Additional
information can also be found at www.ClinicalTrials.gov.
About Non-Small Cell Lung Cancer
Lung cancer, both small cell and non-small cell, is the leading cause of cancer death for both
men and women. According to the American Cancer Society (ACS), more people die of lung
cancer than of colon, breast, and prostate cancers combined. Data from the ACS estimates
that about 215,000 new cases of lung cancer were diagnosed in the United States in 2008 and
approximately 162,000 people will die from this disease. The vast majority of all lung cancers
are the non-small cell type. Prognosis for patients is primarily based on the time of diagnosis
relative to the stage of the cancer. There are several treatment options to choose from
depending on the stage of the cancer, patient's age and common side effects. Treatment can
consist of surgery, radiation, chemotherapy, and new therapies that target the tumor blood
vessel growth.
About Deforolimus
ARIAD's lead product candidate, deforolimus, is a novel rapamycin analog that specifically and
potently inhibits mTOR, a downstream activator of the PI3K/Akt and nutrient sensing pathways.
The mTOR protein acts as a "master switch" in cancer cells. Blocking mTOR creates a
starvation-like effect in cancer cells by interfering with cell growth, division, metabolism, and
angiogenesis. Multiple Phase 1 and Phase 2 clinical trials of deforolimus in solid tumors and
hematologic cancers have completed, or are in the process of patient enrollment. The global
11
Phase 3 SUCCEED trial of oral deforolimus in metastatic soft-tissue and bone sarcomas is
based on a Special Protocol Assessment agreed upon by the U.S. Food and Drug
Administration. ARIAD has a global partnership with Merck & Co., Inc. to develop and
commercialize deforolimus in patients with cancer.
About ARIAD
ARIAD's vision is to transform the lives of cancer patients with breakthrough medicines. The
Company's mission is to discover, develop and commercialize small-molecule drugs to treat
cancer in patients with the greatest and most urgent unmet medical need - aggressive cancers
where current therapies are inadequate. ARIAD's lead product candidate, deforolimus, is an
investigational mTOR inhibitor in Phase 3 clinical development in patients with advanced
sarcomas and is being developed in collaboration with Merck & Co., Inc. ARIAD's second
product candidate, AP24534, is an investigational multi-targeted kinase inhibitor in Phase 1
clinical development in patients with hematological cancers. ARIAD has an exclusive license to
pioneering technology and patents related to certain NF-κB cell-signaling activity, which may
be useful in treating certain diseases. For additional information about the Company, please
visit http://www.ariad.com.
This press release contains "forward-looking statements." Forward-looking statements are
based on management's expectations and are subject to certain factors, risks and
uncertainties that may cause actual results, outcome of events, timing and performance to
differ materially from those expressed or implied by such statements. These risks and
uncertainties include, but are not limited to, preclinical data and early-stage clinical data that
may not be replicated in later-stage clinical studies, the costs associated with our research,
development, manufacturing and other activities, the conduct, timing and results of pre-clinical
and clinical studies of our product candidates, the adequacy of our capital resources and the
availability of additional funding, and other factors detailed in the Company's public filings with
the U.S. Securities and Exchange Commission. The information contained in this press
release is believed to be current as of the date of original issue. The Company does not intend
to update any of the forward-looking statements after the date of this document to conform
these statements to actual results or to changes in the Company's expectations, except as
required by law.
3月4日
Safer Methadone Use For Treatment Of Pain And Addiction
New findings may significantly improve the safety of methadone, a drug widely used to treat
cancer pain and addiction to heroin and other opioid drugs, according to researchers at
Washington University School of Medicine in St. Louis and the University of Washington in
Seattle.
The researchers discovered that the body processes methadone differently than previously
believed. Those incorrect assumptions about methadone have been making it difficult for
physicians to understand how and when the drug is cleared from the body and may be
responsible for unintentional under- or overdosing, inadequate pain relief, side effects and
12
even death.
For many years, methadone has been a mainstay in the treatment of opioid addiction. Taken
orally, it suppresses withdrawal and reduces cravings. In recent years, doctors have
prescribed methadone more frequently as an effective treatment for acute, chronic and cancer
pain. Use of the drug for pain treatment rose 1,300 percent between 1997 and 2006. As more
methadone was prescribed, however, adverse events increased by approximately 1,800
percent, and fatalities were up more than 400 percent (from 786 to 3,849) between the years
1999 and 2004.
"Unfortunately, increased methadone use for pain has coincided with a significant increase in
adverse events and fatalities related to methadone," says principal investigator Evan D.
Kharasch, M.D., Ph.D., an anesthesiologist and clinical pharmacologist at Washington
University School of Medicine and Barnes-Jewish Hospital in St. Louis. "The important
message is that guidelines used by clinicians to direct methadone therapy may be incorrect."
Kharasch, the Russell D. and Mary B. Shelden Professor and director of the Division of Clinical
and Translational Research in Anesthesiology at the School of Medicine, and his colleagues
report the findings in the March issue of the journal Anesthesiology and online in the journal
Drug and Alcohol Dependence.
The investigators wanted to understand how protease inhibitors, drugs that keep the immune
system functioning in patients with HIV, interact with methadone. For years, the enzyme
P4503A was believed to be responsible for clearing methadone from the body. But when
healthy volunteers were given a low dose of methadone together with protease inhibitors that
caused profound decreases in the activity of P4503A, there was no reduction in the clearance
of methadone.
There were two reasons to study what happened to methadone when taken together with
those drugs: First, HIV-AIDS patients may receive methadone for pain and, in some cases, for
accompanying substance abuse problems, along with one or more protease inhibitors. In
addition, many protease inhibitors interact with the P4503A enzyme that traditionally was
thought to be important to methadone clearance. In these studies, Kharasch and his team
looked at interactions among methadone, the P4503A enzyme in the intestine and liver and
the protease inhibitors nelfinavir, indinavir and ritonavir.
They gave study volunteers a combination of the protease inhibitors ritonavir and indinavir.
Both drugs profoundly inhibited the actions of the enzyme. If that enzyme were responsible for
methadone clearance, then inhibiting it should have caused methadone to build up in the body.
But the researchers found that it had no effect on methadone levels.
Volunteers in the second study received the protease inhibitor nelfinavir. Again, the drug
inhibited the action of the P4503A enzyme. That should have meant methadone
concentrations would rise, but they actually decreased by half.
13
"For more than a decade, practitioners have been warned about drug interactions involving the
enzyme P4503A that might alter methadone metabolism," Kharasch says. "The package insert
says inhibiting the enzyme may cause decreased clearance of methadone, but our research
demonstrates that P4503A has no effect on clearing methadone from the body. So the
package insert appears to be incorrect, or certainly needs to be reevaluated, as do guidelines
that explain methadone dosing and potential drug interactions."
That can be dangerous, Kharasch explains, because a clinician may prescribe too much or too
little methadone for patients taking drugs that interact with P4503A, having been informed that
they also would influence methadone clearance. Too little methadone will not relieve pain. Too
much can contribute to the unintentional build-up of methadone in the system, which can
cause slow or shallow breathing and dangerous changes in heartbeat. Physicians could be
unintentionally prescribing methadone incorrectly.
"The highest risk period for inadequate pain therapy or adverse side effects is during the first
two weeks a patient takes methadone," Kharasch says. "If we can provide clinicians with better
dosing guidelines, then I believe we will be able to better treat pain and limit deaths and other
adverse events."
About a dozen related liver enzymes are part of the P450 family, and Kharasch believes
another enzyme from that family may be the one actually involved in methadone metabolism
and clearance. His laboratory is determined to identify the correct enzyme to limit over-and
under-dosing of patients taking methadone to improve addiction and pain treatment as well as
patient safety. Currently, he's testing the related enzyme P4502B. Laboratory studies and
preliminary clinical results indicate that P4502B may be involved, but he says more clinical
research is needed.
"The research also is important for the treatment of HIV-AIDS," Kharasch says. "Protease
inhibitors can interfere with the activity of P4503A but increase the activity of P4502B. This
paradox is highly unusual, and because these two enzymes metabolize so many prescription
drugs, there are many potential drug interactions that we'll be able to understand better if we
can get a better handle on how these pathways absorb drugs into the system and clear them
from the body."
Notes:
Kharasch ED, Walker A, Whittington D, Hoffer C, Sheffels Bedynek P. Methadone metabolism
and clearance are induced by nelfinavir despite inhibition of cytochrome P4503A (CYP3A)
activity. Drug and Alcohol Dependence, in press, available online Feb. 18, 2009.
doi:10.1016/j.drugalcdep.2008.12.009
Kharasch ED, Hoffer C, Whittington D, Walker A, Sheffels Bedynek P. Methadone
pharmacokinetics are independent of cytochrome P4503A (CYP3A) activity and
14
gastrointestinal drug transport. Anesthesiology, vol. 110 (3), pp. 660-672. March 2009. doi:
10.1097/ALN.0b013e3181986a9a
This research was supported by grants from the National Institute on Drug Abuse of the
National Institute of Health and by an NIH grant to the University of Washington General
Clinical Research Center.
Washington University School of Medicine's 2,100 employed and volunteer faculty physicians
also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of
Medicine is one of the leading medical research, teaching and patient care institutions in the
nation, currently ranked third in the nation by U.S. News & World Report. Through its
affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is
linked to BJC HealthCare.
Affiliated with Barnes-Jewish Hospital and St. Louis Children's Hospital, members of BJC
HealthCare.
Source: Jim Dryden
3月4日
New Type Of Vaccination Engineered That Provides Instant Immunity
The experiments, thus far performed only in mice, appear to overcome a major drawback of
vaccinations - the lag time of days, or even weeks, that it normally takes for immunity to build
against a pathogen. This new method of vaccination could potentially be used to provide
instantaneous protection against diseases caused by viruses and bacteria, cancers, and even
virulent toxins.
The work is being published in the Early Edition of the Proceedings of the National Academy of
Sciences (PNAS) the week of March 2, 2009.
The team, led by Scripps Professor Carlos Barbas, III, Ph.D., tested the vaccination method called covalent immunization - on mice with either melanoma or colon cancer.
The scientists injected these mice with chemicals specifically designed to trigger a
programmable and "universal" immune reaction. They developed other chemicals, "adapter"
molecules," that recognized the specific cancer cells. Once injected into the animal, the
adapter molecules self-assembled with the antibodies to create covalent antibody-adapter
complexes.
"The antibodies in our vaccine are designed to circulate inertly until they receive instructions
from tailor-made small molecules to become active against a specific target," Barbas says.
"The advantage of this method is that it opens up the possibility of having antibodies primed
and ready to go in the time it takes to receive an injection or swallow a pill. This would apply
whether the target is a cancer cell, flu virus, or a toxin like anthrax that soldiers or even civilian
populations might have to face during a bioterrorism attack."
15
Only those mice that received both the vaccine and the adapter compound generated an
immediate immune attack on the cancer cells that led to significant inhibition of tumor growth.
This is the first time that such a covalent vaccine has been successfully designed and tested typically, antibodies do not bind to chemicals in this covalent fashion.
The current breakthrough builds on work the Barbas laboratory has been engaged in for the
past few years on chemically programmed monoclonal antibodies, a new class of therapeutics
that the group invented. In this type of therapy, small, cell-targeting molecules and
non-targeting catalytic monoclonal antibodies self-assemble to target pathogens. Monoclonal
antibodies are produced in the laboratory from a single cloned B-cell - the immune system cell
that makes antibodies - to bind to a specific substance. Three clinical trials are now under way
by Pfizer to test the therapeutic effectiveness of this new type of therapy in cancer and
diabetes. The antibodies in the antibody-adapter complex are monoclonal antibodies
engineered to link themselves to adapter molecules.
The Search for the Ideal Vaccination
The practice of vaccination has been extraordinarily successful in controlling certain diseases,
but there are drawbacks. Vaccine development can be an educated guessing game - in the
case of the flu, for example, scientists must study worldwide outbreak patterns to anticipate
which type of flu might strike a particular area. In addition, the most common vaccination
strategies use whole proteins, viruses, or other complex immunogens - not just the specific
part of the macromolecule that is recognized by the immune system - to elicit an immune
response, which makes for wasted immune activity. Then there is the body's own kinetics - the
time it takes to mount a disease-relevant immune response to immunogens limits the speed
with which immunity can be achieved. Finally, age-related declines in the ability to mount
strong immune responses to biological-based vaccines present another challenge to the
effectiveness of such vaccines.
Barbas's chemical-based - rather than biological based - approach to vaccine development
addresses many of these challenges.
"Our approach differs from the traditional vaccine approach in the sense that when we design
an antibody-adapter compound we know exactly what that compound will react with," Barbas
says. "The importance of this is best exemplified with HIV. In current vaccines, many
antibodies are generated against HIV, but most are not able to target the active part of the
virus."
In the near term, Barbas will apply his covalent vaccination approach to HIV, cancer, and
infectious diseases for which no vaccines currently exist. A particular focus will be creating
adapter molecules specific to these diseases.
"We believe that chemistry-based vaccine approaches have been underexplored and may
16
provide opportunities to make inroads into intractable areas of vaccinology," Barbas says.
In addition to Barbas, co-authors of the paper, "Instant immunity through chemically
programmable vaccination and covalent self-assembly," are Mikhail Popkov (who is first
author), Beatriz Gonzalez, and Subhash C. Sinha, all of The Scripps Research Institute.
Notes:
The study was funded by the Skaggs Institute for Chemical Biology and the National Institutes
of Health.
About The Scripps Research Institute
The Scripps Research Institute is one of the world's largest independent, non-profit biomedical
research organizations, at the forefront of basic biomedical science that seeks to comprehend
the most fundamental processes of life. Scripps Research is internationally recognized for its
discoveries in immunology, molecular and cellular biology, chemistry, neurosciences,
autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development.
Established in its current configuration in 1961, it employs approximately 3,000 scientists,
postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and
administrative and technical support personnel. Scripps Research is headquartered in La Jolla,
California. It also includes Scripps Florida, whose researchers focus on basic biomedical
science, drug discovery, and technology development.
Source: Mika Ono
3月4日
Pancreatic Cancer Detection Using Optical Techniques
Optical technology developed by a Northwestern University professor of biomedical
engineering has been shown to be effective in detecting the presence of pancreatic cancer
through analysis of neighboring tissue in the duodenum, according to clinical trial results
published in the journal Disease Markers.
The promising new technology -- which researchers hope could help raise the extremely low
survival rate of pancreatic cancer patients by aiding early detection -- uses novel
light-scattering techniques to analyze extremely subtle changes in the cells of the duodenum,
part of the small intestine neighboring the pancreas. The cells are obtained through a
minimally invasive endoscopy.
The study shows that cells that appear normal using traditional microscopy techniques do
show signs of abnormality when examined using the Northwestern technique, which provides
cell analysis on the much smaller nanoscale.
17
The technology was developed by Vadim Backman, professor of biomedical engineering at the
McCormick School of Engineering and Applied Science at Northwestern, and Vladimir
Turzhitsky, a graduate student in Backman's lab. Clinical trials have been conducted in
collaboration with Hemant Roy, M.D., director of gastroenterology research at NorthShore
University HealthSystem, and Randall Brand, M.D., a gastroenterologist at the University of
Pittsburgh Medical Center.
In the study of 203 patients, the technique accurately discriminated with 95 percent sensitivity
between healthy patients and those with differing stages of the disease. (Only 5 percent of
patients were found to have been diagnosed with false negatives after testing.) The specificity
of the testing group was 71 percent. These results confirm those of an earlier study of 51
patients published in August 2007 in the journal Clinical Cancer Research.
The larger number of patients in the more recent study allowed researchers to calculate the
"area under the receiver operator characteristic" (AUROC), which is an analysis of the
accuracy of the test in distinguishing healthy samples from diseased samples. While the
sensitivity and specificity of tests may vary based on the threshold set by researchers for
diagnosis, the AUROC measures the overall efficacy of the diagnostic technique. The analysis
showed an 85 percent AUROC for the Northwestern method. (Clinically sound tests typically
have an AUROC greater than 70 percent.)
The study in Disease Markers also reports promising results in detecting mucinous cyst
lesions, which are a precursor to cancer. If confirmed in further clinical trials, this approach
may lead to a method for early diagnosis.
Pancreatic cancer is among the most deadly forms of cancer, with a five-year survival rate of
just 5 percent. It is so deadly, in part, because early detection is difficult. There is a high risk of
complications if the pancreas is examined directly, so routine inspections for at-risk patients
usually are not an option. In fact, only 7 percent of people with pancreatic cancer are
diagnosed in the earliest stages of the disease, when the cancer is still confined to its primary
site. More than half of all people with the disease are not diagnosed until the cancer has
already metastasized.
"Typically, by the time a patient is diagnosed with pancreatic cancer, it is too late for the most
successful treatments," says Backman. "Our hope is that this technology will provide a better
method for early diagnosis of the disease, which could greatly improve the survival rate."
The technology combines two complementary optical techniques, four-dimensional elastic
light-scattering fingerprinting (4D-ELF) and low-coherence enhanced backscattering
spectroscopy (LEBS). The researchers found that the two combined work better than one
alone in pancreatic cancer screening.
During the test, a xenon lamp shines intense, white light through a series of lenses and filters
onto the specimen -- cells from the duodenum. The light refracts through the outermost layer
18
of tissues and scatters into a spectrograph, a device that separates a beam of white light into
its component wavelengths and measures them. An image sensor captures the result, then a
computer analyzes the pattern of light scattering, looking for the "fingerprint" of carcinogenesis
in the nanoarchitecture of the cells.
The technology makes use of a biological phenomenon known as the "field effect," a
hypothesis that suggests the genetic and environmental milieu that results in a neoplastic
lesion in one area of an organ should be detectable throughout the organ and even in
neighboring tissue.
If similar results are found when the technique is applied to other organs, the method could
have broad impact on the timely treatment of breast cancer, lung cancer and other forms of
cancer.
The original technology was supported by the National Science Foundation; clinical trials were
supported by the National Institutes of Health and the V Foundation for Cancer Research.
"I'm very excited about the Backman group's work," says Leon Esterowitz, NSF biophotonics
program director. "I believe these results are very promising, and the technique has a high
probability of success for not just detecting early pancreatic cancer but also pre-cancer, so
doctors can go ahead and treat the patient while there's still a chance to defeat the disease.
For pancreatic cancer, this could lead to not only an excellent prognosis, but perhaps even a
cure."
In a related study published last month in the OSA journal Optics Letters, Backman, Roy and
Brand reported promising results for another optical technique called partial wave
spectroscopy. That technology measures how light propagates through a cell in a single
dimension, allowing researchers to detect nanoscopic changes to the interior architecture of a
cell. In this study, researchers examined actual pancreatic cells, gathered using fine needle
aspiration.
"We are developing a suite of optical technologies that we hope will transform our ability to
detect cancer at its earliest stages," says Backman.
Source: Megan Fellman
3月5日
Brain tumor treatment may increase number of cancer
stem-like cells
A new study suggests that the standard treatment for a common brain tumor increases the
aggressiveness of surviving cancer cells, possibly leaving patients more vulnerable to tumor
19
recurrence. The research, published by Cell Press in the March 6th issue of the journal Cell
Stem Cell, provides valuable insight into the molecular mechanisms that enable cancer
stem-like cells to escape cytotoxic treatment and repopulate the tumor.
Glioblastoma multiforme is the most prevalent and aggressive form of primary brain tumor
and is notoriously resistant to standard therapies. Dr. Eric Holland, from Memorial
Sloan-Kettering Cancer Center in New York, examined the role of ABCG2, a protein linked
with drug resistance, in glioma cancer stem-like cells. "ABC proteins are transporters that
participate in tumor resistance by actively transporting drugs across the cell membrane,
serving to protect cells from chemotherapeutic agents," offers Dr. Holland.
Dr. Holland and colleagues employed a method that allowed visualization of ABC-mediated
efflux of fluorescent dye to identify and isolate "side population" (SP) cells from mouse and
human glioblastomas. "Because the SP phenotype in glioma cancer stem-like cells is mainly
mediated by ABCG2, as shown by the almost complete abolition of this phenotype when
ABCG2 activity is blocked, we subsequently studied the oncogenic potential of ABCG2,"
explains Dr. Holland.
The researchers confirmed that SP cells are highly tumorigenic, have the ability to self-renew,
and are resistant to chemotherapy. These results verified that ABCG2 activity, although not
by itself oncogenic, is a marker for glioma stem-like cells. Further, the researchers identified
a detailed molecular mechanism that modulates the activity of ABCG2 and enhances the
ability of cancer stem-like cells to expel drugs.
Importantly, Dr. Holland's group also found that the chemotherapeutic drug temozolomide,
the standard treatment for gliomas, increased the number of glioma cells with stem-like
characteristics. The researchers speculated that because temozolomide is not an ABCG2
substrate, the increase in the SP fraction likely resulted from enrichment of cells with
stem-like properties. "In the process of increasing the number of cells in tumors with
stem-like properties, temozolomide may render surviving cells even more resistant to
subsequent treatment with drugs that are substrates for ABCG2," explains Dr. Holland.
###
The researchers include Anne-Marie Bleau, Dolores Hambardzumyan, Tatsuya Ozawa, Elena
I. Fomchenko, Jason T. Huse, Cameron W. Brennan, and Eric C. Holland, of the Memorial
Sloan-Kettering Cancer Center, New York, NY.
3月5日
'Personalized' genome sequencing reveals coding error
in gene for inherited pancreatic cancer
20
Scientists at the Sol Goldman Pancreatic Cancer Research Center at the Johns Hopkins
Kimmel Cancer Center have used "personalized genome" sequencing on an individual with a
hereditary form of pancreatic cancer to locate a mutation in a gene called PALB2 that is
responsible for initiating the disease. The discovery marks their first use of a genome
scanning system to uncover suspect mutations in normal inherited genes.
The findings, they say, underscore the value of so-called "personalized genome" sequencing,
which decodes a person's genes and compares the changes to those found in healthy people.
"Gene sequencing has always had the potential to help us learn if a person is susceptible to
certain diseases," says Alison Klein, Ph.D., director of the National Familial Pancreas Cancer
Tumor Registry at Johns Hopkins. "By finding the genetic error responsible for this patient's
pancreatic cancer, our team has provided an excellent example of the power of this
approach."
The coding error in PALB2, which stands for "partner and co-localizer of BRCA2" causes a
shortened version of the protein encoded by this gene, rendering it incapable of working with
another cancer-related gene, BRCA2, to repair broken DNA. Mutations in BRCA2 are also
known to cause hereditary forms of cancer.
Klein and her team caution that their finding has not yet resulted in a clinical test for the
hereditary pancreas cancer gene, but laboratories at Johns Hopkins and possibly elsewhere
will be developing one, which she says can be used to increase cancer surveillance for early
signs of disease in those at risk.
Reporting their findings in the March 5 edition of Science Express, the Johns Hopkins
researchers say they sequenced genes taken from a person with pancreatic cancer whose
sister also had the disease, suggesting an inherited predisposition. "Generally, we need data
from very large families to identify the inherited gene, and that was not available in this
case," says Siân Jones, Ph.D., research associate at the Johns Hopkins Kimmel Cancer Center.
Instead, the investigators used high-powered computer software to scan all known
protein-coding genes in the patient -- approximately 20,000 of them – to find more than
15,000 variations.
Most of the variations were normal ones coding for such things as eye or hair color, but the
search was designed to track down particular mutations that caused certain proteins to be
shortened, a process that commonly occurs in cancer, says James Eshleman, M.D., Ph.D.,
associate professor of pathology and oncology.
The search yielded one gene variant, PALB2, resulting from a substitution of a single DNA
letter coding for cytosine with a different one that codes for thymidine.
The research team then scanned for the PALB2 gene in 96 other individuals with pancreatic
cancer who each had at least one relative with pancreatic cancer. Three of them had coding
errors in the PALB2 gene that shortened the protein in a similar way. She estimates that three
21
percent of people with hereditary pancreatic cancer have mutations in PALB2, making it the
second most common gene mutation in these patients after BRCA2.
The investigators believe that their approach could be used to identify inherited alterations
that predispose people to other types of cancer as well as other genetic-based diseases. "The
more information we have about normal variants, the easier it will be to find disease-causing
ones," says Michael Goggins, M.D., professor of pathology, medicine and oncology at Johns
Hopkins.
In the future, scanning genomes for hereditary disease-causing genes could become
"reasonably routine," according to Bert Vogelstein, M.D., an investigator at the Howard
Hughes Medical Institute and co-director of the Ludwig Center at Johns Hopkins.
The investigators say that the cost to determine the sequence of all genes in an individual for
this project was approximately $150,000, but that this cost will likely decrease considerably
in the future.
###
Funding for this project was provided by the Lustgarten Foundation for Pancreatic Cancer
Research, the Sol Goldman Pancreatic Cancer Research Center, the Virginia and D.K. Ludwig
Fund for Cancer Research, the National Institutes of Health and the Michael Rolfe Pancreatic
Cancer Foundation.
In addition to Klein, Eshleman, Goggins and Vogelstein, investigators who conducted the
research include, Ralph Hruban, Mihoko Kamiyama, Michael Borges, Xiaosong Zhang, D.
Williams Parsons, Jimmy Cheng-Ho Lin, Emily Palmisano, Keiran Brune, Elizabeth Jaffee,
Christine Iacobuzio-Donahue, Anirban Maitra, Giovanni Parmigiani, Scott Kern, Victor
Velculescu, and Kenneth Kinzler from Johns Hopkins.
3月5日
Gemin X Initiates Phase 2 Clinical Study Of Obatoclax In
Combination With Standard Chemotherapy For First-Line
Treatment Of Small Cell Lung Cancer
Gemin X Pharmaceuticals, a clinical stage biopharmaceutical company developing novel,
targeted cancer therapeutics, today announced the initiation of a Phase 2 clinical trial of its
lead product candidate obatoclax (GX15-070) for the treatment of patients with
extensive-stage small cell lung cancer (SCLC). In this multi-center, randomized, open-label
Phase 2 study, clinical effect of a combination of carboplatin, etoposide and obatoclax (the
"CEO" regimen) will be compared to the standard chemotherapeutic therapy of carboplatin
and etoposide alone (the control arm) in patients with SCLC. The primary endpoint of the study,
expected to enroll approximately 150 patients with SCLC, is comparison of overall response
rate (ORR) for the obatoclax-containing arm versus the control arm. Secondary endpoints
22
include comparison of progression free survival (PFS) and overall survival (OS), as well as
safety.
"We are very pleased to begin this Phase 2 study in small cell lung cancer in accordance with
our broad development plan for obatoclax, which also includes Phase 2 trial initiations this
year in acute lymphoblastic leukemia and systemic mastocytosis," said Glenn Gormley, M.D.,
Ph.D., President and Chief Executive Officer at Gemin X. "We are encouraged by the striking
synergy observed between obatoclax and carboplatin and etoposide in preclinical studies and
by the dramatic responses seen to-date in the vast majority of SCLC patients in our ongoing
Phase 1b trial. It is our hope that obatoclax's differentiated mechanism will lead to substantial
improvements in response to treatment, tolerability and survival for these cancer patients."
The ongoing Phase 1b dose-escalation portion of this study established safety and identified
the recommended dose for obatoclax, when administered in combination with standard doses
of carboplatin and etoposide as both front-line and second-line therapy. This Phase 1b trial
showed a significant response rate for the small cell lung cancer patients dosed with the
obatoclax-chemotherapy combination after two cycles of therapy, based on RECIST measures.
In the Phase 2 study, each patient in the obatoclax combination arm will receive three-hour
infusions on three consecutive days of dosing every three weeks over six treatment cycles
(provided there is no evidence of disease progression or intolerability). Patients enrolled into
the obatoclax combination arm of the study and who have not progressed after six treatment
cycles will continue to receive obatoclax alone as maintenance therapy after completion of
combination chemotherapy. The trial is expected to be completed by the fourth quarter of this
year.
"The Phase 1 data using obatoclax in combination with carboplatin and etoposide
demonstrated how these drugs can be combined safely, and the early efficacy data are
promising. Oncologists have been looking for a combination that could improve on the results
with carboplatin and etoposide in small cell lung cancer for many years, and the Phase 2
randomized study that has just begun will provide a good test of just what the addition of
obatoclax can do," said Alberto A. Chiappori, M.D., Associate Professor at the H. Lee Moffitt
Cancer Center & Research Institute. "Based on the fact that small cell lung cancers often
express prosurvival Bcl-2 family proteins, and that the combination with obatoclax has
demonstrated synergy in vitro, this study of obatoclax combined with carboplatin and
etoposide is an exciting opportunity for improving the treatment of small cell lung cancer."
About Obatoclax
Obatoclax, Gemin X's potential first-in-class small molecule antagonist of Bcl-2, is specifically
designed to inhibit all relevant members of the Bcl-2 family of proteins, including the dominant
member, Mcl-1. Inhibition of Mcl-1 and other Bcl-2 related proteins enhances cancer cell death
by facilitating apoptosis and/or autophagy. These proteins have been shown to have a
pro-survival effect in malignant cells; thus their inhibition by obatoclax could increase the
23
activity of the drug's tumor killing effect. Obatoclax has been shown to activate cancer cell
death in vitro, to exhibit anti-tumor activity in animal models, and to enhance the effects of
chemotherapy in various models including with the drugs carboplatin and etoposide. It has
also shown single-agent biological and clinical activity in Phase 1 studies in a variety of cancer
indications. Further, obatoclax has demonstrated an early ability to mechanistically evade the
resistance built up by cancer cells to traditional chemotherapeutic agents.
Gemin X's global development plan for obatoclax is focused on diseases marked by
up-regulation of Mcl-1, including small cell lung cancer (in combination with carboplatin and
etoposide), refractory acute lymphoblastic leukemia (in combination with dexamethosone) and
systemic mastocytosis (as a single agent).
Small Cell Lung Cancer
Small cell is an aggressive form of lung cancer, and accounts for about 15% of all lung cancer
cases, according to the American Cancer Society. Chemotherapy alone or combined with
radiation is the usual treatment of choice for small cell lung cancer. According to the Journal of
Clinical Oncology, the median survival time is approximately nine to 12 months with currently
available therapies and the five-year survival rate for patients with extensive stage SCLC is
less than 1%. Improved diagnostic and surgical techniques and novel combination therapies
that can further extend patient survival are desperately needed to positively impact these
outcomes.
About Gemin X Pharmaceuticals
Gemin X is developing first-in-class cancer therapeutics based on reinitiating programmed cell
death, or apoptosis, inducing cancer cell self-digestion, or autophagy, and the inhibition of
metabolism in cancerous cells. Gemin X currently has several clinical development programs
underway, including Phase 2 clinical trials for its lead product candidates obatoclax
(GX15-070), an innovative pan Bcl-2 inhibitor, and GMX1777, a novel inhibitor of NAD+
synthesis, and preclinical studies for its Telomere Capping and SMAC Mimetic programs.
Potential treatment indications for the full scope of pipeline programs span a broad range of
hematological and solid tumors, including chronic lymphocytic leukemia (CLL), melanoma,
small cell lung cancer (SCLC), refractory acute lymphoblastic leukemia (ALL) and systemic
mastocytosis. Founded in 1998, Gemin X is privately held with drug development and
executive headquarters in Malvern, Pennsylvania and drug discovery operations in Montréal,
Canada.
3月5日
'Baby Boom' Carpenters At Greatest Risk Of Developing Asbestos
Related Cancer
One in 17 British carpenters born in the 1940s will die of mesothelioma - a cancer of the lining
of the lung caused by asbestos - according to new research[1]* published in the British Journal
24
of Cancer.
In the largest global study of its kind - funded by Cancer Research UK and the Health and
Safety Executive (HSE) - more than 600 patients with mesothelioma and 1 400 healthy people
were interviewed to examine UK rates of the disease linked to different occupations.
The researchers have calculated that men born in the 1940s who worked as carpenters for
more than 10 years before they reached 30 have a lifetime risk for mesothelioma of about one
in 17. For plumbers, electricians and decorators born in the same decade who worked in their
trade for more than 10 years before they were 30, the risk is one in 50 and for other
construction workers one in 125.
For every case of mesothelioma, asbestos also causes about one case of lung cancer so the
overall risk of asbestos related cancer for this particular group of carpenters is about one in 10.
The risk was also increased in other industries and the study showed that two-thirds of all
British men and one quarter of women had worked in jobs involving potential asbestos
exposure at some time in their lives. There was also a small increased risk in those who had
lived with someone who had been exposed to asbestos.
The risk of mesothelioma for the rest of the UK population who haven't experienced these
occupational exposures is about one in 1,000 and these apparently unexposed cases account
for 60 per cent of all mesotheliomas in women** and 15 per cent in men.
Professor Julian Peto, Cancer Research UK epidemiologist and lead researcher based at the
London School of Hygiene and Tropical Medicine, said: "The UK has the highest death rate
from mesothelioma in the world. The risk is highest in people who were exposed to asbestos
before age 30. By getting information on all the jobs people had ever done we have shown that
the risk in some occupations, particularly in the building industry, is higher than we previously
thought.
"New regulations introduced in 1970 reduced exposure to asbestos in factories but heavy
exposure to the much larger workforce in construction and various other industries continued."
Steve Coldrick, Head of HSE's Disease Reduction Programme, said: "The Health and Safety
Executive and Cancer Research UK commissioned this research to learn more about the
impact of asbestos related cancers upon our workforce, but particularly for those born in the
1940s who have potentially been more exposed to asbestos than later born tradesmen. This
research demonstrates that HSE has been correctly targeting the workers who are most at risk
to asbestos exposure. HSE remains committed to raising awareness of the dangers of working
with asbestos through our work streams and activities such as the 'Hidden Killer' campaign."
"We must continue to remember that asbestos maintained in good condition on-site is not a
threat unless it's disturbed and the fibres become airborne. Also, other potential 'risk factors'
25
such as residence in certain types of housing, living near industrial sites, or engagement in DIY
activity, were not associated with an increased risk."
"In 2010, the second part of this research should provide more information about the role of
amosite in causing mesothelioma in the younger generation. This is underway now and will
provide valuable information about the extent of recent exposure levels (compared to past
exposure levels) on our future tradesmen."
There are three main types of asbestos - white, blue and brown. White asbestos was the type
most commonly used in the UK. Blue asbestos was not used in Britain after 1970, but the use
of brown asbestos continued into the 1980s, and carpenters often cut and drilled brown
asbestos insulation board with power tools. The researchers believe this was a major factor
underlying Britain's mesothelioma epidemic.
There are just over 2 100 people diagnosed with mesothelioma in the UK each year with about
five times as many cases in men as in women.
Dr Lesley Walker, Cancer Research UK's director of information, said: "This research is
important in revealing who is at greatest risk from asbestos exposure. We now need to ensure
that accurate information for workers and regulation of the asbestos still in buildings keeps
pace with what we've learned."
Notes
1. *Occupational, domestic and environmental mesothelioma risk in the British population: a
case-control study. BJC
**This is higher than the overall rate in women in most other countries, suggesting that many of
these unexplained cases were caused by unrecognised environmental asbestos exposures
which occurred in certain situations because of the widespread use of asbestos during the
1960s and 1970s.
2. There are two types of cancer related to asbestos use, mesothelioma and asbestos related
lung cancer.
3. Lifetime risk for carpenters born in the 1940s who did more than 10 years of relevant work
before the age of 30 is 5.9 per cent, 2 per cent for plumbers, electricians and decorators and
0.8 per cent for other construction workers (born in the 1940s).
4. The HSE Board has overall responsibility for occupational health and safety regulations in
Great Britain, and HSE and Local Authorities are the enforcing authorities that work in support
of the Board. For more information on health and safety at work visit
http://www.hse.gov.uk[2][2] Information on worker involvement can be found at
http://www.hse.gov.uk/involvement/[3]
26
5. For more information on asbestos or the Hidden Killer campaign, visit
http://www.hse.gov.uk/asbestos/hiddenkiller/[4] During the last campaign period (Oct / Nov 08
over 530 000 information packs were distributed via HSE and its partner organisations and
HSE's Infoline received averages of 380 calls a day in October and 375 a day in November.
6. Together with its partners and supporters, Cancer Research UK's vision is to beat cancer.
- Cancer Research UK carries out world-class research to improve understanding of the
disease and find out how to prevent, diagnose and treat different kinds of cancer.
- Cancer Research UK ensures that its findings are used to improve the lives of all cancer
patients.
- Cancer Research UK helps people to understand cancer, the progress that is being made
and the choices each person can make.
- Cancer Research UK works in partnership with others to achieve the greatest impact in the
global fight against cancer. For further information about Cancer Research UK's work or to find
out how to support the charity, please call 020 7009 8820 or visit
http://www.cancerresearchuk.org.uk[5].
7. The British Journal of Cancer (BJC) is owned by Cancer Research UK. Its mission is to
encourage communication of the very best cancer research from laboratories and clinics in all
countries. Broad coverage, its editorial independence and consistent high standards have
made BJC one of the world's premier general cancer journals. http://www.bjcancer.com[6]
Cancer Research UK
3月5日
Northeast U.S. Has Most Brain Cancer Hospitalizations
People in the Northeastern U.S. are one-third more likely than those in the South or West to be
hospitalized for treatment of brain cancer or to have brain cancer when they are hospitalized
for another illness or complication, according to the latest News and Numbers from the U.S.
Agency for Healthcare Research and Quality.
In 2006, about 30 of every 100,000 people in the Northeast were hospitalized with brain cancer.
That compares to 23 per 100,000 for people in both the South and West. The rate was slightly
higher for people in the Midwest 25 per 100,000.
AHRQ's analysis also shows that in 2006:
-- Nationally, the hospitalization rate for brain cancer remained stable since 1995 roughly about
35,000 hospital stays a year.
-- An additional 38,000 hospital admissions were associated with brain cancer mostly for
chemotherapy or radiotherapy to continue treatment, or for convulsions, pneumonia or other
27
complication from the disease. These hospitalizations increased 18 percent since 1995.
-- Among people over 65, men were 62 percent more likely to be hospitalized primarily for
brain cancer and 55 percent more likely to be hospitalized with brain cancer as a secondary
diagnosis than were women.
-- While 6.2 percent of hospital patients admitted for brain cancer died while hospitalized in
1995, the rate dropped to 4.4 percent in 2006.
This AHRQ News and Numbers is based on data in Hospitalizations for Brain Cancer, 2006.
The report uses statistics from the 2006 Nationwide Inpatient Sample, a database of hospital
inpatient stays that is nationally representative of inpatient stays in all short-term, non-Federal
hospitals. The data are drawn from hospitals that comprise 90 percent of all discharges in the
United States and include all patients, regardless of insurance type, as well as the uninsured.
Agency for Healthcare Research and Quality (AHRQ)
540 Gaither Rd.
Rockville
MD 20850
United States
3月6日
Brain tumors: New therapy surprisingly successful
Patients survived on average one third longer
This release is available
in German.
The combination of two drugs produces a critical improvement in the
treatment of certain brain tumours. This has been demonstrated by
researchers at Bonn University working in co-operation with German and
Swiss colleagues in a current study. They treated 39 patients who had been
diagnosed with a so-called gliablastoma. The patients survived on average
23 months; with the standard therapy the mean would have been 14.6 months.
Glioblastomas are the most aggressive and the commonest brain tumours.
Left untreated, they prove fatal within just a few weeks. The study has
been published in the Journal of Clinical Oncology (doi:
10.1200/JCO.2008.19.2195).
Even today, glioblastomas are untreatable – something which even the new
combination therapy cannot change. Nevertheless, Professor Dr. Ulrich
Herrlinger of Bonn University´s Schwerpunkt Klinische Neuroonkologie
28
speaks of an outstanding success: "This unusually manifest extension of
the survival time has surprised even us. Our results offer the opportunity
to improve our grip on this aggressive form of cancer. Now, further
investigations involving a larger number of patients are needed to
optimise this therapy. Planning for this is already in hand in Bonn".
Up to now, doctors have treated glioblastomas using radiotherapy with
concomitant chemotherapy. The "gold standard" for this for the last few
years has been the active agent temozolomide. This is still celebrated
as the most important breakthrough in the treatment of glioblastomas. The
researchers combined this preparation with the drug lomustine. At the same
time, the patients were given radiotherapy. The 39 patients thus treated
survived the tumour for an average of 23.1 months. With the standard
therapy, this time is over one third shorter. Seven patients even survived
for over four years.
Genes decide the Success of the Therapy
It would appear that certain changes in the genotype are critical for the
success of this therapy. "With eleven participants in the study, the
information of one gene had been subjected to a characteristic
modification", Ulrich Herrlinger declares. "These patients survived on
average a good 34 months. With the other patients, these drugs appeared
to bring no apparent advantage vis-à-vis pure radiotherapy – at least,
not in the dosage we tested. It is possible that a simple gene test could
decide for whom a concomitant chemotherapy might be of benefit". One
disadvantage of the new method are the side-effects. However, these mostly
occur during the several months of the treatment phase. "After that they
normally disappear completely, and the patients have no further
complaints about them", Herrlinger stresses.
Working in co-operation with the Life&Brain-Zentrum in Bonn, the search
is now on for more compatible, more effective, drugs. "Amongst other
things, we now want to use cell cultures from original tumours to study
precisely what the preparations we used in the study really effect", Dr.
Martin Glas, one of the authors of the study, declares.
###
Long-Term Survival of Patients With Glioblastoma Treated With
Radiotherapy and Lomustine Plus Temozolomide. Martin Glas, Caroline
Happold, Johannes Rieger, Dorothee Wiewrodt, Oliver Bähr, Joachim P.
Steinbach, Wolfgang Wick, Rolf-Dieter Kortmann, Guido Reifenberger,
Michael Weller, and Ulrich Herrlinger. Journal of Clinical Oncology,
Februar 2009
29
3月6日
New National Health And Medical Research Council Alcohol
Guidelines Reduce Your Cancer Risk, Australia
Australian men who drink alcohol should reduce their cancer risk by adhering to new National
Health and Medical Research Council (NHMRC) guidelines and limit their daily intake to no
more than two standard drinks, Cancer Council Australia said today (6 March 2009).
Commenting on the NHMRC's new Australian alcohol guidelines for low-risk drinking, Cancer
Council Australia's Chief Executive Officer, Professor Ian Olver, said adhering to the new
guidelines, which halved the recommendation for men in the previous guidelines, would
significantly reduce cancer risk.
"More than 2800 Australians are diagnosed with alcohol-related cancers each year and
around 1400 die as a result," Professor Olver said. "Any alcohol consumption carries some
cancer risk, and the more you drink the higher the risk. Alcohol may seem an accepted part of
Australian cultural life, but people need to know that drinking incurs a significant cancer risk.
Moderating consumption means moderating risk."
Professor Olver said alcohol increased the risk of cancers of the mouth, throat, oesophagus,
bowel, liver and female breast. There was no evidence of alcohol consumption having a
protective effect against any cancer.
He said halving the recommended daily limit from four drinks to two for Australian men should
send a message that drinking can cause serious short and long-term harm. The authority of
the NHMRC, Australia's peak government body for developing health advice, would hopefully
persuade men who drank to limit their alcohol consumption.
"While Cancer Council Australia would have preferred the recommended daily limit for women
to have been reduced from two standard drinks to one, the guidelines are a big step in the right
direction," Professor Olver said.
"Alcohol consumption can significantly raise cancer risk in women, as it is an important cause
of breast cancer in women of all ages and can also increase breast cancer risk in
postmenopausal women by leading to weight gain. Women need to be particularly cautious
about their intake."
Professor Olver said the guidelines were for guidance only and that alcohol-free days would
also reduce risk.
He said the guidelines' aim of fostering an informed approach to countering Australia's harmful
drinking culture was consistent with the Government's proposed "alcopops" tax, which had
been shown to reduce net alcohol consumption.
30
3月6日
NICE Refuses Funding For Advanced Breast Cancer
NICE issued its final appraisal determination advising against NHS funding for Tyverb®
(lapatinib), a treatment for an aggressive form of advanced breast cancer (ErbB2-positive).1
Lapatinib (in combination with Xeloda® [capecitebine]) offers a new treatment option for
women whose disease has returned despite treatment with standard chemotherapies and
Herceptin® (trastuzumab).2 There are very few treatment options available for these women
and lapatinib offers a chance of additional time without their disease progressing.3 Lapatinib is
the only licensed ErbB2 targeted treatment* for these patients.
GlaxoSmithKline (GSK) will consider appealing the decision. Simon Jose, General Manager,
GSK UK commented; "We disagree with the NICE decision and believe Tyverb is a valuable
and important treatment for eligible women. In recognition of the cost effectiveness challenges
with drugs that treat patients with a short life expectancy, we offered the Tyverb Patient
Access Programme to help ensure it was made available on the NHS. It is difficult to comment
without the appearance of self interest. However, there is clearly more work to be done by all
parties when flexible access programmes from industry and the recent changes by NICE for
patients with a short life expectancy still fail to give them access to valuable medicines."
GSK proposed the patient access programme in the UK when NICE indicated early on in its
review that it did not consider lapatinib to be cost effective in treating this patient population. In
an effort to achieve a positive outcome for patients and greater value to the NHS, GSK bears
the cost of lapatinib, for all eligible patients under the scheme, for up to the first 12 weeks of
treatment. The NHS would commence payment only for the patients who continue to receive
clinical benefit beyond 12 weeks. GSK will continue to honour the patient access programme
for NHS trusts in the UK.
During the lapatinib assessment NICE proposed new advice for the assessment of treatments
in small patient populations with a short life expectancy.4 Lapatinib is licensed for a particular
type of breast cancer that affects around 2000 women a year.1Therefore lapatinib qualified for
review under the new advice.
GSK submitted a sub-group analysis that met the overall survival criterion of this new NICE
advice. However NICE concluded that whilst the data analysis could be useful in guiding future
research, as it stands it would not change their conclusions. NICE's decision reflects the
difficulty in demonstrating significant survival benefits in patients at this advanced stage of
disease.1 Furthermore, trials are often halted early for ethical reasons to allow patients to
cross over to the
active arm because of the effectiveness demonstrated by the medicine under study, as in the
case of lapatinib.5
In its final appraisal determination NICE acknowledges that lapatinib is a clinically effective
31
option, noting that lapatinib plus capecitabine demonstrated improved time to progression
(TTP) and progression free survival (PFS) - significantly delaying the progression of the cancer
and controlling the disease.1
GSK's NICE submission demonstrated that lapatinib, in conjunction with the patient access
programme, could actually save the NHS money in patients who would have received
trastuzumab (Herceptin®) containing regimens. NICE acknowledged this is the majority (>50%)
of eligible patients, however NICE concluded that trastuzumab is not likely to be cost effective
in this setting and therefore lapatinib plus capecitabine would not be cost effective.
Safety Information
Lapatinib plus capecitabine is generally well tolerated. The most common adverse events
associated with lapatinib plus capecitabine were diarrhoea, rash, nausea, vomiting, fatigue
and hand-foot syndrome.2,3 Diarrhoea and rash were more common with the combination
whilst the incidence of hand-foot syndrome was similar between the two treatment groups.2 A
decrease in left ventricular ejection fraction (LVEF) was reported by 2.5% of patients receiving
lapatinib plus capecitabine vs. 1% of patients on capecitabine alone.2 Hepatobiliary events
(mainly raised liver enzymes and/or bilirubin levels) have been reported commonly in
association with lapatinib plus capecitabine therapy.2 Lapatinib has also been associated with
reports of pulmonary toxicity.2
About Tyverb
- Tyverb, in combination with capecitabine, is indicated for the treatment of patients with
advanced or metastatic breast cancer whose tumours overexpress ErbB2 (HER2). Patients
should have progressive disease following prior therapy which must include anthracyclines
and taxanes and therapy with trastuzumab in the metastatic setting.2
- Healthcare professionals should refer to the Tyverb Summary of Characteristics (SPC) for full
prescribing information, including warnings and precautions.2
- * Tyverb received a conditional marketing authorisation in Europe, June 2008.2
GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare
companies - is committed to improving the quality of human life by enabling people to do more,
feel better and live longer. For further information please visit http://www.gsk.com
Tyverb® is a registered trademark of the GlaxoSmithKline group of companies. Herceptin®
and Xeloda® are registered trademarks of F. Hoffmann-La Roche
GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare
companies - is committed to improving the quality of human life by enabling people to do more,
feel better and live longer.
32
3月6日
Idera Pharmaceuticals Scientists Co-Author Paper On Preclinical
Data Of Investigational Cancer Vaccine
Idera Pharmaceuticals, Inc. (Nasdaq: IDRA), a biotechnology company engaged in the
discovery and development of DNA- and RNA-based drug candidates targeted to Toll-like
Receptors (TLR), today announced the publication of a paper entitled "Treatment of Mammary
Carcinomas in HER-2 Transgenic Mice through Combination of Genetic Vaccine and an
Agonist of Toll-like Receptor 9" in Clinical Cancer Research (2009, 15, 1575-84) co-authored
by scientists from Idera and Merck & Co., Inc. The paper describes a preclinical study
evaluating a TLR9 agonist as a vaccine adjuvant in combination with a HER-2/neu plasmid
DNA electroporation/adenovirus vaccine candidate.
In this preclinical study, a novel TLR9 agonist was evaluated for its ability to enhance the
effects of a HER-2/neu plasmid DNA electroporation/adenovirus vaccine. In a tumor model the
combination of HER-2/neu genetic vaccine and TLR9 agonist showed potent antitumor activity
associated with antibody isotype switch and antibody-dependent cellular cytotoxicity activities.
"Under our collaboration with Merck, we have created novel agonists of TLR7, 8 and 9 for use
as adjuvants in candidate vaccines for cancer, infectious diseases and Alzheimer's disease.
We are pleased with this demonstration that an agonist of TLR9 enhances the activity of an
investigational genetic cancer vaccine in preclinical studies," commented Sudhir Agrawal,
D.Phil., Chief Executive Officer and Chief Scientific Officer of Idera.
About the Collaboration
Idera Pharmaceuticals, Inc. entered into an exclusive license and research collaboration
agreement with Merck & Co., Inc. in December 2006 to research, develop and commercialize
vaccine products containing Idera's agonist compounds targeting TLRs 7, 8, and 9 in the fields
of oncology, infectious diseases and Alzheimer's disease. As part of the agreement, the two
companies engaged in a two-year research collaboration to generate novel agonists targeting
TLR7 and TLR8 incorporating both Merck and Idera chemistry for use in the licensed fields. In
November 2008, Merck extended its research collaboration with Idera for an additional year.
About Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals develops drug candidates to treat infectious diseases, autoimmune and
inflammatory diseases, cancer, and respiratory diseases, and for use as vaccine adjuvants.
Our proprietary drug candidates are designed to modulate specific Toll-like Receptors, which
are a family of immune system receptors that direct immune system responses. Our
pioneering DNA and RNA chemistry expertise enables us to create drug candidates for
internal development and generates opportunities for multiple collaborative alliances. For more
information, visit http://www.iderapharma.com.
33
Idera Forward Looking Statements
This press release contains forward-looking statements concerning Idera Pharmaceuticals, Inc.
that involve a number of risks and uncertainties. For this purpose, any statements contained
herein that are not statements of historical fact may be deemed to be forward-looking
statements. Without limiting the foregoing, the words "believes," "anticipates," "plans,"
"expects," "estimates," "intends," "should," "could," "will," "may," and similar expressions are
intended to identify forward-looking statements. There are a number of important factors that
could cause Idera's actual results to differ materially from those indicated by such
forward-looking statements, including whether products based on Idera's technology will
advance into or through the clinical trial process on a timely basis or at all and receive approval
from the United States Food and Drug Administration or equivalent foreign regulatory agencies;
whether, if the Company's products receive approval, they will be successfully distributed and
marketed; whether the Company's collaborations with Novartis, Merck & Co., and Merck
KGaA will be successful; whether the patents and patent applications owned or licensed by the
Company will protect the Company's technology and prevent others from infringing it; whether
Idera's cash resources will be sufficient to fund the Company's operations; and such other
important factors as are set forth under the caption "Risk Factors" in Idera's Quarterly Report
on Form 10-Q filed on November 13, 2007, which important factors are incorporated herein by
reference. Idera disclaims any intention or obligation to update any forward-looking
statements.
3月6日
Lexicon Presents Clinical Data On LX1032 For Carcinoid Syndrome
At European Neuroendocrine Tumor Society Meeting
Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company focused on
discovering and developing breakthrough treatments for human disease, announced that Dr.
Philip Brown, senior vice president of clinical development at Lexicon, delivered an oral
presentation at the annual meeting of the European Neuroendocrine Tumor Society (ENETS).
The presentation summarized Phase 1 clinical trial results for LX1032, Lexicon's
orally-delivered small molecule drug candidate for managing gastrointestinal symptoms
associated with carcinoid syndrome. The clinical studies, conducted to date in healthy
volunteers, indicated that the drug candidate reduced serotonin levels in humans as predicted
by Lexicon's mouse models and preclinical research. Lexicon is planning to initiate a Phase 2
clinical trial of LX1032 in patients with carcinoid syndrome in the first quarter of 2009.
A copy of the presentation will be available on the company's corporate website at
http://www.lexpharma.com.
About ENETS
The ENETS conference is a medical conference focused on diagnosis and treatment of
neuroendocrine tumors including carcinoid. The meeting brings together leading
34
neuroendocrine tumor experts from around the world in such fields as oncology, pathology,
radiology, nuclear medicine, endocrinology, surgery and gastroenterology. The 2009 ENETS
conference runs from March 5-7 in Granada, Spain.
About Carcinoid Syndrome and LX1032
Carcinoid syndrome is a chronic condition that is the result of metastatic neuroendocrine
tumors that usually originate from the gastrointestinal tract. These tumors secrete large
amounts of serotonin, which can cause a variety of symptoms including severe diarrhea and
abdominal discomfort. LX1032 acts to reduce serotonin production by inhibiting tryptophan
hydroxylase (TPH), a key enzyme in the synthesis of serotonin.
LX1032 is being developed in a product development collaboration with Symphony Capital
Partners, L.P. and its co-investors.
About Lexicon
Lexicon is a biopharmaceutical company focused on discovering and developing breakthrough
treatments for human disease. Lexicon currently has five drug candidates in development for
autoimmune disease, carcinoid syndrome, diabetes, glaucoma and irritable bowel syndrome,
all of which were discovered by the company's research team. The company has used its
proprietary gene knockout technology to identify more than 100 promising drug targets.
Lexicon has focused drug discovery efforts on these biologically-validated targets to create its
extensive pipeline of clinical and preclinical programs. For additional information about
Lexicon and its programs, please visit http://www.lexpharma.com.
Safe Harbor Statement
This press release contains "forward-looking statements," including statements relating to
Lexicon's clinical development of LX1032 and the potential therapeutic and commercial
potential of LX1032. This press release also contains forward-looking statements relating to
Lexicon's growth and future operating results, discovery and development of products,
strategic alliances and intellectual property, as well as other matters that are not historical facts
or information. All forward-looking statements are based on management's current
assumptions and expectations and involve risks, uncertainties and other important factors,
specifically including those relating to Lexicon's ability to successfully conduct clinical
development of LX1032 and preclinical and clinical development of its other potential drug
candidates, advance additional candidates into preclinical and clinical development, obtain
necessary regulatory approvals, achieve its operational objectives, obtain patent protection for
its discoveries and establish strategic alliances, as well as additional factors relating to
manufacturing, intellectual property rights, and the therapeutic or commercial value of its drug
candidates, that may cause Lexicon's actual results to be materially different from any future
results expressed or implied by such forward-looking statements. Information identifying such
important factors is contained under "Factors Affecting Forward-Looking Statements" and
35
"Risk Factors" in Lexicon's annual report on Form 10-K for the year ended December 31, 2007,
as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to
update or revise any such forward-looking statements, whether as a result of new information,
future events or otherwise.
Lexicon Pharmaceuticals, Inc.
3月6日
The Most Successful Treatment For Rectal Cancer Is Radiation
Therapy, Followed By Optimum Surgery
The findings in two articles published in this week´s edition of The Lancet, indicate that high
quality surgery following a short period of radiation therapy is the best treatment for patients
with operable rectal cancer.
Surgery is the standard treatment for rectal cancer, however the removal of the tumor alone
does not eliminate the risk of the cancer recurring in the same area. Recurrence is difficult to
treat and incurable in most patients. Earlier research showed that radiotherapy and
chemotherapy, before or after surgery, reduce the local reappearance of the cancer. However,
radiotherapy is an expensive treatment and is linked to the increased risk of other lasting
complications, such as impaired bowel function, incontinence, and sexual dysfunction. For that
reason, radiotherapy should be targeted to patients showing a high risk of local recurrence,
such as those with involvement of the circumferential resection margin.
In order to obtain additional verification, Professor Robert Steele and his team carried out the
Medical Research Council (MRC) CR07 and the National Cancer Institute of Canada (NCIC)
C016 trial. This study evaluated the choice in using chemo radiotherapy in patients who had
involvement of the circumferential resection margin, with one week sessions of radiotherapy
prior to surgery. From March 1998 to August 2005, 1,350 patients with rectal cancer were
recruited from the UK, Canada, South Africa and New Zealand. Patients were given randomly
five daily treatments of radiotherapy before surgery, or twenty five treatments of chemo
radiotherapy after surgery, to those with high risk of local recurrence.
After three years, findings concluded that in the pre-operative radiotherapy group, 4.4 percent
of the patients had local recurrence of the cancer in comparison to 10.6 percent in the
post-operative group. At three years, the probability of disease-free survival was of 77.5
percent in the pre-operative radiotherapy patients and of 72 percent in the post-operative
patients. The general survival rate did not vary considerably among the groups (330 patients
died; 157 in the pre-operative radiotherapy group, 173 in the selective post-operative chemo
radiotherapy group).
Total mesorectal excision is one of the latest advances in surgical techniques that have
enhanced patient outcomes. Phil Quirke, University of Leeds, UK, and team evaluated the
consequences of circumferential resection margin and the plane of surgery (amount of tissue
36
removed around the tumor) achieved during surgery on local recurrence of cancer. The study
included 1,156 patients in the MRC CR07 and NCIC-CTG C016 trial.
Results indicated that 11 percent (128) of the patients had involvement of the circumferential
resection margin, and the plane of surgery was ranked as good (mesorectal) in 52 percent
(604), intermediate (intramesorectal) in 34 percent (398), and poor (muscularis propria plane)
in 13 percent (154).
Low recurrence rates were related to a negative circumferential resection margin and a
superior plane of surgery. After three years, there was local recurrence for 6 percent of
patients with a negative circumferential margin, in comparison to 17 percent of patients with a
positive circumferential margin. Moreover, 4 percent of patients in the mesorectal group had
local recurrence, 7 percent of patients in the intramesorectal group, and 13 percent of patients
in the muscularis propria plane group. Still, short-course radiotherapy prior to surgery lowered
recurrence by nearly half, for any plane of surgery achieved.
"At present, only 50% of rectal cancer surgery is done in the mesorectal plane, suggesting that
a further decrease in local recurrence rates might be obtained by improving the plane of
surgery achieved…[This could] be achieved through education and surgical tuition", the
authors write.
Dr Robert Madoff, University of Minnesota, Minneapolis, USA, in a supplementary remark,
says these findings confirm: "That preoperative radiation can mitigate but not eliminate the
adverse effects of imperfect surgery. The best outcomes occurred when preoperative radiation
was followed by optimum surgery…The next challenge is to understand which patient needs
what therapy to maximise his or her chance for cure."
The Lancet
3月7日
New Research Sheds Light On How Stem Cells Turn Into Blood
Cells
Researchers funded by the Canadian Cancer Society have discovered how certain messages
that are carried within stem cells can trigger those cells to become blood cells. The findings
were published online on the 5th March 09 in Cell Stem Cell.
"This finding is exciting because it may provide a new way to make blood from human stem
cells that could be used to regenerate the blood system in patients, including those with
leukemia or those undergoing cancer treatments that indirectly destroy the immune and blood
system," says Dr. Christine Williams, Director of Research Programs at the Canadian Cancer
Society Research Institute.
This is the first time researchers have been able to show the importance of one particular cell
37
pathway - known as the noncanonical Wnt pathway - in prompting stem cells to specialize and
become blood cells. The pathway appears to organize the stem cells so that they can respond
to signals telling them what to turn into.
Dr. Mick Bhatia, who led the study, received a $750,000 grant from the Canadian Cancer
Society for this research. "By directing cell differentiation, this method provides the most
efficient way to produce blood cells that we are aware of to date," he says. Dr. Bhatia is
director of the McMaster University Stem Cell and Cancer Research Institute.
Stem cells are the building blocks of every organ and tissue in the body. These cells have the
remarkable ability to become any type of cell in the body including bone, muscle and blood
cells.
Notes:
The Canadian Cancer Society is a national community-based organization of volunteers
whose mission is the eradication of cancer and the enhancement of the quality of life of people
living with cancer. It is the largest national charitable funder of cancer research in Canada.
Last year, the Society funded close to $49.5 million in leading-edge research projects across
the country. To know more about cancer, visit the website at http://www.cancer.ca or call the
toll-free, bilingual Cancer Information Service at 1 888 939-3333.
Source:
Christine Harminc
Senior Communications Officer
3月8日
Researchers discover gene mutations that cause
childhood brain cancer
May lead to better drug treatments
March 8, 2009 TORONTO – Researchers funded by the Canadian Cancer Society
have discovered eight similar genes that, when mutated, appear to be
responsible for medulloblastoma – the most common of childhood brain
cancers. The findings are published today in the online edition of the
journal Nature Genetics.
"This discovery is very promising and may help researchers develop better,
more targeted treatments so that more of these children will survive and
fewer will suffer debilitating side effects," says Dr. Christine Williams,
38
Director of Research Programs, Canadian Cancer Society Research
Institute.
Dr. Michael Taylor, who has a $600,000 research grant from the Canadian
Cancer Society, led the study: "When these eight genes are functioning
normally, we believe their role is to make a protein which tells the
developing brain when it's time to stop growing. But when the genes are
mutated, the brain may continue to grow out of control, leading to cancer.
"Drugs are already being developed that target these types of proteins,"
he says. "Our hope is that some of these drugs may be adapted and used
effectively to treat medulloblastomas." Dr. Taylor is a pediatric brain
surgeon at Toronto's Hospital for Sick Children:
In the study, the largest of its kind, researchers looked at more than
200 tumour samples. The samples came from children in countries all over
the world including Canada, the US, England, Poland and Saudi Arabia. Paul
Northcott, a PhD student in Dr Taylor's lab, analyzed and interpreted all
the data over a period of 3 ½ years. "We've learned more from this study
about the genetic basis of this disease than from any other previous
study," Northcott says. The gene mutations they found had not been
suspected as culprits in cancer formation.
About 250 Canadian children are diagnosed with various types of brain
cancer every year. About 70 per cent of these survive. Brain tumours are
the leading cause of childhood cancer deaths. The most common childhood
brain cancer is medulloblastoma – a tumour that occurs at the back of
the brain in the cerebellum. It is primarily a disease of very young
children and is particularly deadly among babies under 18 months of age.
In Canada, about 40 children are diagnosed with medulloblastoma every year
and half of these will survive.
Many survivors experience serious physical and neurological problems from
the disease itself and from the effects of very aggressive treatments on
the developing brain. Treatments include surgery, radiation and
chemotherapy.
###
The Canadian Cancer Society is a national community-based organization
of volunteers whose mission is the eradication of cancer and the
enhancement of the quality of life of people living with cancer. It is
the largest national charitable funder of cancer research in Canada. Last
year, the Society funded close to $49.5 million in leading-edge research
projects across the country. To know more about cancer, visit the website
39
at www.cancer.ca or call the toll-free, bilingual Cancer Information
Service at 1 888 939-3333.
3月9日
Freezing kidney cancer: Hot treatment should be new
gold standard for destroying small tumors
More than 75 percent of patients diagnosed have small renal cell tumors; safe
interventional radiology treatment shown near 100 percent effective in destroying
localized tumors, says Johns Hopkins study
SAN DIEGO, Calif. (March 9, 2009)—Freezing kidney tumors—using a safe
minimally invasive interventional radiology treatment that kills the
cancer 100 percent effectively without surgery—should be the gold
standard or first treatment option for all individuals with tumors that
are 4 centimeters in size or smaller. And, this treatment—interventional
cryoablation—is a viable option for people with larger tumors, according
to two studies presented at the Society of Interventional Radiology's 34th
Annual Scientific Meeting.
"Interventional cryoablation is as effective as laparoscopic surgery
(partial nephrectomy), the current gold standard treatment, and
laparoscopic cryoablation surgery for treating renal cell carcinoma,"
said Christos Georgiades, M.D., Ph.D., interventional radiologist at
Johns Hopkins Hospital in Baltimore, Md. "We can eliminate a cancer—that
once it metastasizes can be notoriously difficult to treat and has a low
chance of cure—with a simple outpatient procedure. Eliminating cancer
at such an early stage is truly significant news for kidney cancer
patients," he added.
It's important that individuals realize all their treatment
options—especially since the incidence of kidney cancer has been
steadily increasing in this country over the past 30 years, said
Georgiades. Approximately 54,000 people are diagnosed with kidney cancer
each year—with nearly 13,000 dying from it annually, according to recent
statistics. Most people with this cancer are older, and the overall
lifetime risk of getting kidney cancer is about 1 in 75—with men at higher
risk than women. More than 75 percent of individuals who are diagnosed
with kidney cancer have small tumors that are discovered incidentally.
40
"Cryoablation is a great treatment option that doctors should discuss with
patients early on," he explained.
The Hopkins studies, examining the safety and efficacy of percutaneous
(no incision) cryoablation, show the treatment's powerful results. "Based
on the results of our three-year study, we have shown that interventional
cryoablation for kidney cancer should be the gold standard or the first
treatment option for all patients whose tumors are 4 centimeters or
smaller. It should be a viable option for patients whose cancer is even
larger than that. And, ablation (or freezing) is a very effective option
for patients who cannot or do not want to have surgery," noted Georgiades.
Cryoablation's efficacy rate—the ratio of how many patients' renal cell
carcinoma was destroyed completely for localized tumors by size—is 100
percent up to 4 centimeters (about 2 inches) and nearly 100 percent up
to 7 centimeters (about 3 inches). Three localized 10-centimeter (about
4 inches) tumors—large tumors that are typically removed
surgically—were treated; in two cases the tumor was successfully killed.
"This news is especially significant for individuals with small tumors,
since more than 75 percent of patients who are diagnosed with kidney cancer
have tumors that are 4 centimeters or less in size," said Georgiades.
"These individuals can have their tumors treated completely, effectively,
without surgery, with quicker recovery and mostly on an outpatient basis.
Whatever the definition of 'cure' is, these results come as close to it
as possible," he noted. "At Hopkins, interventional cryoablation is the
first-line treatment for small tumors. Most of our patients go home the
same day they receive treatment with minimal limitation on regular
activities. With laparoscopic kidney surgery, a patient remains in the
hospital for several days and recovery time can be from two to four weeks,"
he added. "Our studies highlight how effective interventional radiology
treatments can be—not just for kidney cancer—but for other kinds of
cancers and other diseases as well. Interventional radiology treatments
will have a significant impact on the overall survival and benefits that
patients can have from avoiding surgery," said Georgiades.
"There is no question that interventional cryoablation, which uses
imaging to pinpoint tumors and probes to penetrate the skin to deliver
freezing cold directly to a diseased tumor, works. This interventional
treatment is not a widely known procedure yet, even to other doctors, and
some patients are going to have to pursue it on their own," said Georgiades.
The treatment is widely available in the United States at all major
institutions and some smaller institutions as well; it is usually covered
by health insurance.
41
Researchers followed kidney cancer patients who had received cryoablation
for three years—well beyond the established and well-accepted one-year
benchmark within the medical community to gauge the success of a kidney
tumor treatment option—since most kidney tumors would be visible within
a year with a CT scan or MRI. The use of percutaneous cryoablation should
not be limited—as it has been—to patients who have other diseases that
make surgery very high risk, cannot undergo anesthesia, have borderline
kidney function, may only have one kidney or multiple recurring tumors
or do not have any other option, said Georgiades. "There may be a bias
in the medical community—among surgeons, primary care doctors and
urologists—that cryoablation works only for certain patients with small
tumors. This is not the case," emphasized Georgiades.
"Traditionally, laparoscopic surgery has been the main treatment option
for all renal cell cancers; it literally cuts the cancer out. The good
news is that individuals no longer need to have a kidney partially or
completed removed to treat their cancer," noted Georgiades. When
comparing the rate of complications between percutaneous cryoablation and
surgery, Georgiades said that none of the patients who had cryoablation
developed new or metastatic disease and they had fewer complications. The
minimally invasive nature of interventional cryoablation means that it
can be performed with minimal blood loss and without an incision, just
a tiny hole in the skin. The interventional radiology treatment translates
into significantly less pain, a shorter hospital stay and more rapid
recovery. This safe treatment can be repeated, if necessary. The most
common complication is a bruise around the kidney that goes away by itself,
he said.
In studying cryoablation's efficacy, researchers looked at 90 tumors in
84 patients. Efficacy was determined based on a tumor's size at 3-, 6and 12-month clinic visits and then yearly—with follow-up imaging with
CT or MRI scans. Both efficacy and three-year survival rates approach 100
percent overall.
In studying cryoablation's safety, Georgiades studied the results of 101
percutaneous cryoablations on 91 patients who either couldn't undergo
surgery or elected the interventional radiology treatment. Using computed
tomography (CT) imaging, researchers could view tumors and probes in real
time. Interventional cryoablation "has an excellent safety profile," said
Georgiades.
Cryoablation is typically performed under light anesthesia, known as
sedation, by an interventional radiologist who has consulted with the
patient's urologist. One or more hollow needles are inserted through the
skin directly into a tumor. Interventional radiologists can observe and
42
guide the insertion by combined use of ultrasound and CT. The needle, or
cryoprobe, is filled with argon gas, which creates an ice ball, which
rapidly freezes the tumor. The tumor is then thawed by replacing the argon
with helium. The procedure consists of two freezing and one thawing cycle,
seeking a frozen margin beyond the tumor edge to ensure death of the entire
tumor. After the cryoprobe is removed, a small bandage is placed over the
skin puncture site. Cryoablation, which can also be referred to as cryo
or cryotherapy, is approved by the Food and Drug Administration for
treating soft tissue tumors, such as renal cell cancer.
###
More information about kidney cancer, cryoablation and interventional
radiology can be found online at www.SIRweb.org.
Abstract 18: "Percutaneous Cryoablation for Renal Cell Carcinoma:
Safety," K. Hong, J. Geschwind, C. Georgiades, Johns Hopkins
University—vascular and interventional radiology, Baltimore, Md.; R.
Rodriguez, Johns Hopkins University—urology, Baltimore, Md.; and Z.
Cizman, Jefferson University, Philadelphia, Pa., SIR 34th Annual
Scientific Meeting March 7-12, 2009.
Abstract 19, "Percutaneous Cryoablation for Renal Cell Carcinoma:
Efficacy," K. Hong, J. Geschwind, C. Georgiades, Johns Hopkins
University—vascular and interventional radiology, Baltimore, Md.; R.
Rodriguez, Johns Hopkins University—urology, Baltimore, Md.; and Z.
Cizman, Johns Hopkins University—vascular and interventional radiology,
Baltimore, Md., and Jefferson University, Philadelphia, Pa., SIR 34th
Annual Scientific Meeting March 7�, 2009. Both abstracts can be found
at www.SIRmeeting.org.
About Kidney Cancer
Kidney cancer is the eighth most common cancer in men and the tenth in
women. The most common type of kidney cancer is renal cell carcinoma, which
forms in the lining of the renal tubules in the kidney that filter the
blood and produce urine. Approximately 85 percent of kidney tumors are
renal cell carcinomas.
More than 32,000 Americans each year are diagnosed with kidney
cancer—many of them don't have symptoms. Typically, those with kidney
cancer are past the age of 40 and are twice as likely to be men. Other
risk factors include smoking, obesity, high blood pressure, long-term
dialysis and Von Hippel-Lindau syndrome.
43
About the Society of Interventional Radiology
Interventional radiologists are physicians who specialize in minimally
invasive, targeted treatments. They offer the most in-depth knowledge of
the least invasive treatments available coupled with diagnostic and
clinical experience across all specialties. They use X-ray, MRI and other
imaging to advance a catheter in the body, usually in an artery, to treat
at the source of the disease internally. As the inventors of angioplasty
and the catheter-delivered stent, which were first used in the legs to
treat peripheral arterial disease, interventional radiologists pioneered
minimally invasive modern medicine. Interventional oncology is a growing
specialty area of interventional radiology. Interventional radiologists
can deliver treatments for cancer directly to the tumor without
significant side effects or damage to nearby normal tissue.
Today many conditions that once required surgery can be treated less
invasively by interventional radiologists. Interventional radiology
treatments offer less risk, less pain and less recovery time compared to
open surgery. Visit www.SIRweb.org.
An estimated 5,300 people are attending the Society of Interventional
Radiology's 34th Annual Scientific Meeting in San Diego.
3月9日
New staging technique might save bladders in some
bladder cancer patients
MAYWOOD, Ill. -- Pathologists today (March 9, 2009) reported encouraging results from a
new technique to increase the accuracy of staging bladder cancer tumors that could reduce
the need to remove bladders from some patients.
The technique is performed by pathologists before surgery. It can confirm that in certain
cases, tumors are at an early enough stage so that the cancer can be treated without
removing the bladder.
In a study of 70 bladder cancer specimens, the technique was 95.2 percent accurate, Dr.
Gladell Paner of Loyola University Health System reported at a meeting of the United States
and Canadian Academy of Pathology annual meeting in Boston.
The American Cancer Society estimates there were about 69,000 new cases of bladder cancer
in the United States last year, and about 14,000 people died of the disease.
44
There are five stages of bladder cancer, ranging from Stage 0 (earliest) to Stage 4 (most
advanced). Stage 0 and Stage 1 cancers generally do not require removal of the bladder.
Stage 2 and above typically require removal of part of or the entire bladder.
In Stage 0 and Stage 1, the tumor is confined to the surface of the bladder, or just below the
surface. In Stage 2, the tumor has penetrated down to a deep muscle layer. But in some
cases, Stage 2 cancer can look like Stage 1. The reason is that a layer of muscle near the
surface can look like the deep muscle layer. Such a mistake can result in the bladder being
needlessly removed. In as many as 4 percent of biopsies, it is extremely difficult to
distinguish between Stage 1 and Stage 2 cancer, Paner said.
In the new technique, developed by Paner, the specimen is exposed to an antibody called
smoothelin. Smoothelin reacts strongly with deep muscle, and this reaction shows up as a
stain when seen under the microscope. By contrast, smoothelin does not react or leave stains
on muscle near the surface.
"The goal is to avoid the potential mistake of calling a tumor Stage 2 when it actually is Stage
1," Paner said. Paner is an assistant professor in the Department of Pathology at Loyola
University Chicago Stritch School of Medicine.
In Paner's study, the technique correctly identified 97.9 percent of the specimens that had
deep muscle and 95.2 percent of the specimens that did not have deep muscle.
"These results are very encouraging," Paner said. "However, we still need to be cautious. The
technique needs to be studied further."
At the USCAP meeting, Paner and other Loyola researchers are lead authors of 16 study
abstracts and co-authors of another nine abstracts.
The USCAP meeting is the world's largest gathering of physician-pathologists. Researchers
from more than 430 medical schools and universities around the world will present nearly
2,800 study abstracts. Loyola is among the top 20 centers in the number of first-authored
abstracts. All abstracts undergo a blind, peer-reviewed process.
"Your institution has worked hard to support and generate these important studies which will
help advance the specialty of pathology as well as medicine in general," USCAP Executive
Vice President Dr. Fred Silva wrote in a letter to Dr. Eva Wojcik, chair of the Department of
Pathology, Loyola University Chicago Stritch School of Medicine.
###
Based in the western suburbs of Chicago, Loyola University Health System is a quaternary
care system with a 61-acre main medical center campus, the 36-acre Gottlieb Memorial
Hospital campus and 25 primary and specialty care facilities in Cook, Will and DuPage
counties. The medical center campus is conveniently located in Maywood, 13 miles west of
45
the Chicago Loop and 8 miles east of Oak Brook, Ill. The heart of the medical center campus,
Loyola University Hospital, is a 570-licensed bed facility. It houses a Level 1 Trauma Center,
a Burn Center and the Ronald McDonald® Children's Hospital of Loyola University Medical
Center. Also on campus are the Cardinal Bernardin Cancer Center, Loyola Outpatient Center,
Center for Heart & Vascular Medicine and Loyola Oral Health Center as well as the LUC Stritch
School of Medicine, the LUC Marcella Niehoff School of Nursing and the Loyola Center for
Fitness. Loyola's Gottlieb campus in Melrose Park includes the 250-bed community hospital,
the Gottlieb Center for Fitness and the Marjorie G. Weinberg Cancer Care Center.
3月9日
Addition Of Chemotherapy To Radiotherapy Continues To Increase
Survival In Patients With Brain Tumours For Up To 5 Years, The
Lancet
Giving patients with glioblastoma-the most common and aggressive form of primary brain
tumour-the chemotherapy drug temozolomide in combination with radiotherapy increases their
survival compared with those receiving radiotherapy alone and this improvement persists for
up to 5 years, according to the final results of the EORTC-NCIC trial*, published Online first
and in the May edition of The Lancet Oncology.
For over 30 years, post-operative radiotherapy was the standard treatment for glioblastoma,
but offered only modest survival benefits to patients. The average life-expectancy of patients
with glioblastoma was 9-12 months.
In 2004, after many disappointing attempts with drug therapy, the large international phase III
EORTC-NCIC trial finally showed some promising results in this difficult setting where use of
combined treatment with radiotherapy and temozolomide reduced the risk of dying from
glioblastoma by 37% (HR for death 0.63, CI 0.53-0.75) compared with radiotherapy alone. At 2
years, 27% of patients receiving temozolomide in combination with radiotherapy (TMZ/RT)
were alive, compared with just 10% of patients being treated with radiotherapy (RT) alone.
However, whether this survival benefit would persist over time was unknown.
In this study, Roger Stupp and colleagues report the long-term 5-year outcomes of patients
involved in the original EORTC-NCIC trial. The authors also examined whether clinical factors
and the molecular profile of the tumours would identify patients with particularly good survival
or response to chemotherapy.
Findings showed that at 3 years, 16% of patients receiving TMZ/RT were alive compared with
only 4% of patients having RT alone. At 4 years, overall survival data after combined treatment
were 12.1% compared with 3% for RT alone and at 5 years, 9.8% vs 1.9%, respectively.
Importantly, improvement in survival was seen across all clinical prognostic subgroups, even in
patients considered to have a poor diagnosis-such as more elderly patients or patients whose
tumour could not be removed.
46
In exploratory analyses, overall survival data were best in patients being treated with TMZ/RT
whose tumours carried an inactivated MGMT gene (0-6-methylguanine-DNA
methyltransferase). Almost half of these patients were alive after 2 years and they also showed
a persistent survival advantage at 3, 4, and 5 years. The authors suggest that testing tumours
for the methylation status of the MGMT gene would allow the selection of patients most likely
to benefit from this treatment.
Despite this improvement-with a substantial proportion of patients surviving for several years
after treatment with TMZ/RT-most still died. The authors noted no difference in the pattern of
recurrence between patients treated with RT alone or TMZ/RT, and caution that upfront
combined therapy may be effective in reducing tumour bulk and aggressiveness, but it does
not truly modify the natural behaviour of the disease, and thus is unlikely to lead to a cure.
*The EORTC-NCIC (European Organisation for Research and Treatment of Cancer and the
National Cancer Institute of Canada Clinical Trials Group) trial was a randomised trial in which
standard post-operative radiotherapy and standard post-operative radiotherapy combined with
temozolomide followed by up to six cycles of temozolomide were compared in 573 patients
with newly diagnosed glioblastoma.
3月9日
New Therapy Surprisingly Successful For Brain Tumors
The combination of two drugs produces a critical improvement in the treatment of certain brain
tumours. This has been demonstrated by researchers at Bonn University working in
co-operation with German and Swiss colleagues in a current study. They treated 39 patients
who had been diagnosed with a so-called gliablastoma. The patients survived on average 23
months; with the standard therapy the mean would have been 14.6 months. Glioblastomas are
the most aggressive and the commonest brain tumours. Left untreated, they prove fatal within
just a few weeks. The study has been published in the Journal of Clinical Oncology (doi:
10.1200/JCO.2008.19.2195).
Even today, glioblastomas are untreatable - something which even the new combination
therapy cannot change. Nevertheless, Professor Dr. Ulrich Herrlinger of Bonn University´s
Schwerpunkt Klinische Neuroonkologie speaks of an outstanding success: "This unusually
manifest extension of the survival time has surprised even us. Our results offer the opportunity
to improve our grip on this aggressive form of cancer. Now, further investigations involving a
larger number of patients are needed to optimise this therapy. Planning for this is already in
hand in Bonn".
Up to now, doctors have treated glioblastomas using radiotherapy with concomitant
chemotherapy. The "gold standard" for this for the last few years has been the active agent
temozolomide. This is still celebrated as the most important breakthrough in the treatment of
glioblastomas. The researchers combined this preparation with the drug lomustine. At the
same time, the patients were given radiotherapy. The 39 patients thus treated survived the
tumour for an average of 23.1 months. With the standard therapy, this time is over one third
shorter. Seven patients even survived for over four years.
47
Genes decide the Success of the Therapy
It would appear that certain changes in the genotype are critical for the success of this therapy.
"With eleven participants in the study, the information of one gene had been subjected to a
characteristic modification", Ulrich Herrlinger declares. "These patients survived on average a
good 34 months. With the other patients, these drugs appeared to bring no apparent
advantage vis-à-vis pure radiotherapy - at least, not in the dosage we tested. It is possible that
a simple gene test could decide for whom a concomitant chemotherapy might be of benefit".
One disadvantage of the new method are the side-effects. However, these mostly occur during
the several months of the treatment phase. "After that they normally disappear completely, and
the patients have no further complaints about them", Herrlinger stresses.
Working in co-operation with the Life&Brain-Zentrum in Bonn, the search is now on for more
compatible, more effective, drugs. "Amongst other things, we now want to use cell cultures
from original tumours to study precisely what the preparations we used in the study really
effect", Dr. Martin Glas, one of the authors of the study, declares.
Notes:
Long-Term Survival of Patients With Glioblastoma Treated With Radiotherapy and Lomustine
Plus Temozolomide. Martin Glas, Caroline Happold, Johannes Rieger, Dorothee Wiewrodt,
Oliver Bähr, Joachim P. Steinbach, Wolfgang Wick, Rolf-Dieter Kortmann, Guido Reifenberger,
Michael Weller, and Ulrich Herrlinger. Journal of Clinical Oncology, February 2009
3月9日
Discovery Of Gene Mutations That Cause Childhood Brain Cancer
Researchers funded by the Canadian Cancer Society have discovered eight similar genes that,
when mutated, appear to be responsible for medulloblastoma - the most common of childhood
brain cancers. The findings are published in the online edition of the journal Nature Genetics.
"This discovery is very promising and may help researchers develop better, more targeted
treatments so that more of these children will survive and fewer will suffer debilitating side
effects," says Dr. Christine Williams, Director of Research Programs, Canadian Cancer
Society Research Institute.
Dr. Michael Taylor, who has a $600,000 research grant from the Canadian Cancer Society, led
the study: "When these eight genes are functioning normally, we believe their role is to make a
protein which tells the developing brain when it's time to stop growing. But when the genes are
mutated, the brain may continue to grow out of control, leading to cancer.
"Drugs are already being developed that target these types of proteins," he says. "Our hope is
that some of these drugs may be adapted and used effectively to treat medulloblastomas." Dr.
Taylor is a pediatric brain surgeon at Toronto's Hospital for Sick Children:
48
In the study, the largest of its kind, researchers looked at more than 200 tumour samples. The
samples came from children in countries all over the world including Canada, the US, England,
Poland and Saudi Arabia. Paul Northcott, a PhD student in Dr Taylor's lab, analyzed and
interpreted all the data over a period of 3 ½ years. "We've learned more from this study about
the genetic basis of this disease than from any other previous study," Northcott says. The gene
mutations they found had not been suspected as culprits in cancer formation.
About 250 Canadian children are diagnosed with various types of brain cancer every year.
About 70 per cent of these survive. Brain tumours are the leading cause of childhood cancer
deaths. The most common childhood brain cancer is medulloblastoma - a tumour that occurs
at the back of the brain in the cerebellum. It is primarily a disease of very young children and is
particularly deadly among babies under 18 months of age. In Canada, about 40 children are
diagnosed with medulloblastoma every year and half of these will survive.
Many survivors experience serious physical and neurological problems from the disease itself
and from the effects of very aggressive treatments on the developing brain. Treatments include
surgery, radiation and chemotherapy.
Notes:
The Canadian Cancer Society is a national community-based organization of volunteers
whose mission is the eradication of cancer and the enhancement of the quality of life of people
living with cancer. It is the largest national charitable funder of cancer research in Canada.
Last year, the Society funded close to $49.5 million in leading-edge research projects across
the country. To know more about cancer, visit the website at http://www.cancer.ca/.
Source: Christine Harminc
3 月 10 日
Fishing for microdeletions that predispose an embryo
to develop cancer syndromes in later life
Researchers have used a common laboratory technique for the first time to detect genetic
changes in embryos that could predispose the resulting children to develop certain cancer
syndromes. Current preimplantation genetic diagnosis techniques can detect mutations in
very small bits of genes or DNA, but, until now, it wasn't easy to detect deletions involving
whole genes or long sections of DNA in embryos.
The study, published online today (Wednesday 11 March) in Europe's leading reproductive
medicine journal Human Reproduction [1], uses a technique called fluorescent in situ
hybridization (FISH) to detect losses of small parts of whole chromosomes (microdeletions)
in a single cell from an embryo. The work opens the way to test for microdeletions in patients
49
with other genetic conditions as well as the two cancer predisposition syndromes treated in
this study. [2]
Professor Joris Vermeesch, coordinator of the Genomics Core and head of Constitutional
Cytogenetics, and Evelyne Vanneste, a PhD student, both at the Center for Human Genetics,
University Hospital Leuven (Belgium), and their colleagues used FISH to carry out PGD in
embryos from three couples where the women carried microdeletions for either
neurofibromatosis type 1 (NF1) or Von Hippel-Lindau disease (VHL). As a result, the woman
with the VHL mutation gave birth to healthy twins from embryos selected using FISH PGD.
Neurofibromatosis type 1 (also known as Von Recklinghausen disease) is a common inherited
condition with an incidence at birth of one in 3,000-3,500. NF1 patients develop tumours of
the nervous system, pigmented patches of skin and can have lower IQs. In 95% of people
with NF1, a mutation is found in the NF1 gene, which is a tumour suppressor gene; but five
per cent of NF1 patients have microdeletions of the gene, and large microdeletions can result
in more severe symptoms.
Von Hippel-Lindau (VHL) disease is a rarer cancer syndrome, occurring in about one in
36,000 births. Symptoms of the disease include benign tumours of the central nervous
system and benign and malignant tumours of organs such as the kidneys, adrenal glands and
pancreas. It is an inherited condition caused by a mutation in the VHL tumour suppressor
gene.
The strands of DNA that twist together to form the double helix structure are made up of lots
of small sections called nucleotides. The nucleotides are made up of the four DNA bases –
adenine, thymine, guanine and cytosine (or A,T,C,G). Mutations that can be detected by the
conventional PCR (polymerase chain reaction) technique used in PGD are usually mutations
of a single nucleotide or base. A deletion or microdeletion normally involves the loss of larger
numbers of nucleotides.
Prof Vermeesch explained: "Current techniques using PCR to detect abnormalities in embryos
can detect one base, nucleotide or letter change in the DNA, but they cannot be used when a
person has a loss of the whole gene or a lot of letters – a microdeletion. Patients with these
cancer predisposition syndromes, and some other conditions, usually carry only a single
microdeletion. Now, for the first time, we have used FISH to detect these microdeletions in
the embryo and thus can help carriers to create offspring without those anomalies.
"Importantly, microdeletions are not so rare in neurofibromatosis type 1. It is also becoming
clear that genomic disorders caused by microdeletions, duplications and copy number
variations are much more frequent than previously thought. The techniques we have used in
this study will help a wide range of microdeletion carriers."
For each of the three women, the researchers created probes that could be used to identify
NF1 or VHL deletions in the embryos. The embryos were obtained from the women using
normal assisted reproduction techniques. They took two cells from each embryo and
50
performed FISH to probe them for the microdeletions. Only embryos that FISH had identified
as being healthy, without any microdeletions, were transferred to the women's wombs.
Ms Vanneste explained that although they had to make FISH probes specific to each woman,
the NF1 microdeletions found tended to recur. "Therefore, most NF1 patients with a deletion
carry the same deletion and our FISH PGD conditions can be rapidly replicated and re-used in
other deletion carriers. It seems likely that the number of families that can benefit from FISH
PGD will increase in years to come and we are continuing to help more families using this
approach. However, for each condition a new probe has to be made. This is time-consuming,
but we are currently developing tools to identify all similar genetic imbalances with a single
technology."
###
[1] Preimplantation genetic diagnosis using fluorescent in situ hybridization for cancer
predisposition syndromes caused by microdeletions. Human Reproduction.
doi:10.1093/humrep/dep034
[2] PGD can be carried out already to detect a genetic susceptibility for some cancers, but
only if the specific mutation is know (e.g. to detect the BRCA1/2 mutations that can lead to
breast cancer developing). The majority of these cases involve a change in a single nucleotide,
not a microdeletion.
3 月 10 日
Aminoguanidine: An Attractive Line As A Multi-Modal
Avenue To Overcome Tumor
Aminoguanidine is a compound that exerts multiple biological actions. Aminoguanidine has
well described antioxidant properties and is also an inhibitor of nitric oxide synthases, the
enzymes that produce nitric oxide. The nitric oxide molecule has been implicated in different
biological processes associated with both survival and cell death. In vitro, nitric oxide exhibits
cytostatic or cytotoxic effects in cancer cells according to its concentration within the tumor
microenvironment. Although the in vitro action of nitric oxide synthase inhibitors (such as
aminoguanidine) has been extensively studied in tumor cells, little research has been
undertaken as regards their in vivo effects on cancer growth. Pancreatic cancer is a lethal
disease due to its aggressive nature and lack of response to conventional therapy. New
therapeutic modalities are keenly sought.
A research article, published on March 7, 2009 in the World Journal of Gastroenterology,
addresses this problem. This research team, led by Professor Gabriela Martín from the
Laboratory of Radioisotopes, School of Pharmacy and Biochemistry, University of Buenos
Aires, has carried out investigations in cancer biology on the role of histamine and other
growth factors in cell proliferation, differentiation and death, and also in tumor progression, for
more than ten years They have demonstrated that histamine exerts an antiproliferative effect
51
in different human neoplastic cell lines with NO probably being involved in this action. Various
publications have shown the in vitro action of nitric oxide synthase inhibitors (such as
aminoguanidine), the article further investigate the role of aminoguanidine in the in vivo
pancreatic cancer growth.
Human pancreatic cancer xenografted mice were employed for the study. Aminoguanidine
treatment reduced the growth of xenografted tumors in mice, delayed the appearance of
metastases, and enhanced survival.
Aminoguanidine showed an anti-tumoral action evidenced by a lower tumor volume at the end
of treatment, a delayed appearance of palpable metastases and an extended life span. The
antiproliferative action was associated with a lower expression of endothelial nitric oxide
synthase, a reduced NO production, an antiangiogenic effect and also reduced expression of
antioxidant enzymes. This is the first study reporting beneficial effects induced by
aminoguanidine in pancreatic cancer.
Chemoresistance is still the major problem of anticancer drug treatment of malignant diseases,
such as pancreatic carcinoma. In this sense, aminoguanidine could provide an attractive line
of investigation as a multi-modal avenue to overcome the illness due to its different effects on
tumor biology.
Notes:
Reference: Mohamad NA, Cricco GP, Sambuco LA, Croci M, Medina VA, Gutiérrez AS,
Bergoc RM, Rivera ES, Martín GA. Aminoguanidine impedes human pancreatic tumor growth
and metastasis development in nude mice. World J Gastroenterol 2009; 15(9): 1065-1071
http://www.wjgnet.com/1007-9327/15/1065.asp
Correspondence to: Dr. Gabriela A Martín, Laboratory of Radioisotopes, School of Pharmacy
and Biochemistry,University of Buenos Aires, Junín 954 (C1113AAB), Buenos Aires, Argentina.
Source: Lin Tian
3 月 10 日
RNA Interference Toward MMP-2 May Be An Effective
Therapeutic Strategy For Cancer
The invasion or metastasis of pancreatic cancer has been known to be a complex process
involving many molecular mechanisms, of which proteolytic degradation of extracellular matrix
(ECM) exerted by matrix metalloproteinases (MMPs) was considered to be an essential step.
Some data suggest that MMP-2 is involved in pancreatic cancer invasion and metastasis, and
a high level of MMP-2 has been found to correlate with poor prognosis in patients with
pancreatic cancer. Therefore, inhibition of MMP-2 may be of great value in both preventing
pancreatic cancer and blocking metastasis of established tumors.
52
A study published on March 7, 2009 addresses the problem. The research team led by
Professor Song from Department of General Surgery, Affiliated Beijing Tiantan Hospital,
Capital Medical University utilized RNA interference system by using the vector （pGPU6）to
specifically knock down MMP-2 expression in pancreatic cancer cell. MMP-2 expression was
measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Cell
proliferation, apoptosis were examined by MTT, flow cytometry, respectively. The abilities of
adhesion and invasion were detected by cell adhesion assay and cell invasion assay using
Transwell chambers.
Data provide evidence that RNA interference against MMP-2 successfully inhibited the mRNA
and protein expression of MMP-2 in the pancreatic cancer cells line Bxpc-3, leading to a potent
suppression of tumor cells adhesion and invasion without affecting cells proliferation and
apoptosis. These findings suggest that RNA interference towards MMP-2 may be an effective
therapeutic strategy for the clinical management of pancreatic tumor. Although the leap to
clinical practice remains elusive, gene therapy targeting MMP-2 is attractive and warrants
further investigation.
Notes:
Reference: Zhi YH, Song MM, Wang PL, Zhang T, Yin ZY. Suppression of matrix
metalloproteinase-2 via RNA interference inhibits pancreatic carcinoma cell invasiveness and
adhesion. World J Gastroenterol 2009; 15(9): 1072-1078
http://www.wjgnet.com/1007-9327/15/1072.asp
Correspondence to: Dr. Mao-Min Song, Department of General Surgery, Affiliated Beijing
Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Source: Lin Tian
3 月 10 日
Detailed Diagnosis Boosts Child Cancer Survival
More accurate disease classification now means some young children with neuroblastoma will
have less intensive treatment with better survival, according to research published in the
Journal of Clinical Oncology*.
In a pan-European trial, researchers found that screening the tumours of children under the
age of one with advanced neuroblastoma for a gene called MYCN could save them from
unnecessary chemotherapy.
The number of MYCN genes are known to be increased in about 25 per cent of
neuroblastomas. Tumours with increased numbers of this gene behave much more
aggressively.
53
In this trial, 96 per cent of patients whose neuroblastoma had spread to distant parts of the
body but did not have the amplified gene survived five years or more with little or no treatment.
Neuroblastoma affects around 90 children each year in the UK and across the board, five year
survival rates are around 60 per cent. Around 30 children under the age of one are diagnosed
with neuroblastoma each year in the UK.
The study was led by Cancer Research UK's Professor of Paediatric Oncology Professor Andy
Pearson at the Institute of Cancer Research and the Royal Marsden Hospital in Sutton with Dr
Mary Gerrard at Sheffield Children's Hospital and conducted by researchers from the
International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOPEN) and the
Children's Cancer and Leukaemia Group (CCLG).
They treated 170 babies from nine European countries with neuroblastoma that had spread to
distant parts of the body - but who did not have the amplified MYCN gene in their tumours.
These children were treated with up to four courses of chemotherapy. Some children were
treated with surgery first if their doctors felt they needed it.
Previously, these children would have been treated with up to 12 courses of chemotherapy.
Professor Pearson said: "This is very positive news for babies with this type of neuroblastoma.
We saw an excellent outcome in the children we treated who were spared extra therapy and
the side effects that come with it. Chemotherapy can cause children to feel tired, sick and
make it more likely they'll pick up infections, so it's very important to avoid this where possible.
Our current goal is to individualise or personalise treatment for children with neuroblastoma."
The results of this trial suggest that less intense chemotherapy should be given to this group of
babies.
Kate Law, Cancer Research UK's director of clinical trials, said: "Overall, survival rates for
children's cancers have been rapidly improving over the past three decades. But it's crucial we
support trials like this to refine treatments and reduce the long-term side effects that curative
therapies can sometimes cause.
"This study confirms the importance of understanding the personal biology of individual
patients in creating successful, tailored treatment regimes."
Notes
* Significance of MYCN Amplification in International Neuroblastoma Staging System Stage 1
and 2 Neuroblastoma: A Report From the International Neuroblastoma Risk Group Database.
Bagatell et al. Journal of Clinical Oncology.
54
This study was conducted in nine European counties: UK, Italy, France, Spain, Portugal,
Norway, Austria, Belgium and Switzerland.
Stages of neuroblastoma
The stage of a cancer tells the doctor how far it has grown or spread. The stage is important
because it helps the doctor decide which treatment to give.
There are 4 main stages of neuroblastoma, but stages 2 and 4 are divided into two further
groups.
Children in this study were stage 4 or 4S.
Stage 4 means the cancer has spread to parts of the body that are some distance from where
it started. Stage 4S is a special case in children younger than one year old when diagnosed, as
it has a better outlook than other stages and sometimes the cancer goes away without
treatment Neuroblastoma may have spread to the liver or skin, but not to the bones. And no
more than 10 per cent of cells in the bone marrow are neuroblastoma cells.
3 月 10 日
Freezing Kidney Cancer: Hot Treatment Should Be New Gold
Standard For Destroying Small Tumors
Freezing kidney tumors -- using a safe minimally invasive interventional radiology treatment
that kills the cancer 100 percent effectively without surgery -- should be the gold standard or
first treatment option for all individuals with tumors that are 4 centimeters in size or smaller.
And, this treatment -- interventional cryoablation -- is a viable option for people with larger
tumors, according to two studies presented at the Society of Interventional Radiology's 34th
Annual Scientific Meeting.
"Interventional cryoablation is as effective as laparoscopic surgery (partial nephrectomy), the
current gold standard treatment, and laparoscopic cryoablation surgery for treating renal cell
carcinoma," said Christos Georgiades, M.D., Ph.D., interventional radiologist at Johns Hopkins
Hospital in Baltimore, Md. "We can eliminate a cancer -- that once it metastasizes can be
notoriously difficult to treat and has a low chance of cure -- with a simple outpatient procedure.
Eliminating cancer at such an early stage is truly significant news for kidney cancer patients,"
he added.
It's important that individuals realize all their treatment options -- especially since the incidence
of kidney cancer has been steadily increasing in this country over the past 30 years, said
Georgiades. Approximately 54,000 people are diagnosed with kidney cancer each year -- with
nearly 13,000 dying from it annually, according to recent statistics. Most people with this
cancer are older, and the overall lifetime risk of getting kidney cancer is about 1 in 75 -- with
men at higher risk than women. More than 75 percent of individuals who are diagnosed with
kidney cancer have small tumors that are discovered incidentally. "Cryoablation is a great
55
treatment option that doctors should discuss with patients early on," he explained.
The Hopkins studies, examining the safety and efficacy of percutaneous (no incision)
cryoablation, show the treatment's powerful results. "Based on the results of our three-year
study, we have shown that interventional cryoablation for kidney cancer should be the gold
standard or the first treatment option for all patients whose tumors are 4 centimeters or smaller.
It should be a viable option for patients whose cancer is even larger than that. And, ablation (or
freezing) is a very effective option for patients who cannot or do not want to have surgery,"
noted Georgiades. Cryoablation's efficacy rate -- the ratio of how many patients' renal cell
carcinoma was destroyed completely for localized tumors by size -- is 100 percent up to 4
centimeters (about 2 inches) and nearly 100 percent up to 7 centimeters (about 3 inches).
Three localized 10-centimeter (about 4 inches) tumors -- large tumors that are typically
removed surgically -- were treated; in two cases the tumor was successfully killed.
"This news is especially significant for individuals with small tumors, since more than 75
percent of patients who are diagnosed with kidney cancer have tumors that are 4 centimeters
or less in size," said Georgiades. "These individuals can have their tumors treated completely,
effectively, without surgery, with quicker recovery and mostly on an outpatient basis. Whatever
the definition of 'cure' is, these results come as close to it as possible," he noted. "At Hopkins,
interventional cryoablation is the first-line treatment for small tumors. Most of our patients go
home the same day they receive treatment with minimal limitation on regular activities. With
laparoscopic kidney surgery, a patient remains in the hospital for several days and recovery
time can be from two to four weeks," he added. "Our studies highlight how effective
interventional radiology treatments can be -- not just for kidney cancer -- but for other kinds of
cancers and other diseases as well. Interventional radiology treatments will have a significant
impact on the overall survival and benefits that patients can have from avoiding surgery," said
Georgiades.
"There is no question that interventional cryoablation, which uses imaging to pinpoint tumors
and probes to penetrate the skin to deliver freezing cold directly to a diseased tumor, works.
This interventional treatment is not a widely known procedure yet, even to other doctors, and
some patients are going to have to pursue it on their own," said Georgiades. The treatment is
widely available in the United States at all major institutions and some smaller institutions as
well; it is usually covered by health insurance.
Researchers followed kidney cancer patients who had received cryoablation for three years -well beyond the established and well-accepted one-year benchmark within the medical
community to gauge the success of a kidney tumor treatment option -- since most kidney
tumors would be visible within a year with a CT scan or MRI. The use of percutaneous
cryoablation should not be limited -- as it has been -- to patients who have other diseases that
make surgery very high risk, cannot undergo anesthesia, have borderline kidney function, may
only have one kidney or multiple recurring tumors or do not have any other option, said
Georgiades. "There may be a bias in the medical community -- among surgeons, primary care
doctors and urologists -- that cryoablation works only for certain patients with small tumors.
56
This is not the case," emphasized Georgiades.
"Traditionally, laparoscopic surgery has been the main treatment option for all renal cell
cancers; it literally cuts the cancer out. The good news is that individuals no longer need to
have a kidney partially or completely removed to treat their cancer," noted Georgiades. When
comparing the rate of complications between percutaneous cryoablation and surgery,
Georgiades said that none of the patients who had cryoablation developed new or metastatic
disease and they had fewer complications. The minimally invasive nature of interventional
cryoablation means that it can be performed with minimal blood loss and without an incision,
just a tiny hole in the skin. The interventional radiology treatment translates into significantly
less pain, a shorter hospital stay and more rapid recovery. This safe treatment can be repeated,
if necessary. The most common complication is a bruise around the kidney that goes away by
itself, he said.
In studying cryoablation's efficacy, researchers looked at 90 tumors in 84 patients. Efficacy
was determined based on a tumor's size at 3-, 6- and 12-month clinic visits and then yearly -with follow-up imaging with CT or MRI scans. Both efficacy and three-year survival rates
approach 100 percent overall.
In studying cryoablation's safety, Georgiades studied the results of 101 percutaneous
cryoablations on 91 patients who either couldn't undergo surgery or elected the interventional
radiology treatment. Using computed tomography (CT) imaging, researchers could view
tumors and probes in real time. Interventional cryoablation "has an excellent safety profile,"
said Georgiades.
Cryoablation is typically performed under light anesthesia, known as sedation, by an
interventional radiologist who has consulted with the patient's urologist. One or more hollow
needles are inserted through the skin directly into a tumor. Interventional radiologists can
observe and guide the insertion by combined use of ultrasound and CT. The needle, or
cryoprobe, is filled with argon gas, which creates an ice ball, which rapidly freezes the tumor.
The tumor is then thawed by replacing the argon with helium. The procedure consists of two
freezing and one thawing cycle, seeking a frozen margin beyond the tumor edge to ensure
death of the entire tumor. After the cryoprobe is removed, a small bandage is placed over the
skin puncture site. Cryoablation, which can also be referred to as cryo or cryotherapy, is
approved by the Food and Drug Administration for treating soft tissue tumors, such as renal
cell cancer.
More information about kidney cancer, cryoablation and interventional radiology can be found
online at http://www.SIRweb.org.
Abstract 18: "Percutaneous Cryoablation for Renal Cell Carcinoma: Safety," K. Hong, J.
Geschwind, C. Georgiades, Johns Hopkins University--vascular and interventional radiology,
Baltimore, Md.; R. Rodriguez, Johns Hopkins University--urology, Baltimore, Md.; and Z.
Cizman, Jefferson University, Philadelphia, Pa., SIR 34th Annual Scientific Meeting March
57
7-12, 2009.
Abstract 19, "Percutaneous Cryoablation for Renal Cell Carcinoma: Efficacy," K. Hong, J.
Geschwind, C. Georgiades, Johns Hopkins University--vascular and interventional radiology,
Baltimore, Md.; R. Rodriguez, Johns Hopkins University--urology, Baltimore, Md.; and Z.
Cizman, Johns Hopkins University--vascular and interventional radiology, Baltimore, Md., and
Jefferson University, Philadelphia, Pa., SIR 34th Annual Scientific Meeting March 7-12, 2009.
Both abstracts can be found at http://www.SIRmeeting.org.
About Kidney Cancer
Kidney cancer is the eighth most common cancer in men and the tenth in women. The most
common type of kidney cancer is renal cell carcinoma, which forms in the lining of the renal
tubules in the kidney that filter the blood and produce urine. Approximately 85 percent of
kidney tumors are renal cell carcinomas.
More than 32,000 Americans each year are diagnosed with kidney cancer -- many of them
don't have symptoms. Typically, those with kidney cancer are past the age of 40 and are twice
as likely to be men. Other risk factors include smoking, obesity, high blood pressure, long-term
dialysis and Von Hippel-Lindau syndrome.
About the Society of Interventional Radiology
Interventional radiologists are physicians who specialize in minimally invasive, targeted
treatments. They offer the most in-depth knowledge of the least invasive treatments available
coupled with diagnostic and clinical experience across all specialties. They use X-ray, MRI and
other imaging to advance a catheter in the body, usually in an artery, to treat at the source of
the disease internally. As the inventors of angioplasty and the catheter-delivered stent, which
were first used in the legs to treat peripheral arterial disease, interventional radiologists
pioneered minimally invasive modern medicine. Today, interventional oncology is a growing
specialty area of interventional radiology. Interventional radiologists can deliver treatments for
cancer directly to the tumor without significant side effects or damage to nearby normal tissue.
Many conditions that once required surgery can be treated less invasively by interventional
radiologists. Interventional radiology treatments offer less risk, less pain and less recovery time
compared to open surgery. Visit http://www.SIRweb.org.
An estimated 5,300 people are attending the Society of Interventional Radiology's 34th Annual
Scientific Meeting in San Diego.
Society of Interventional Radiology
3 月 11 日
Iron induces death in tumor cells
58
Rapid growth of cancer cells and their frequent divisions have their price: Cancer cells need
considerably more energy than healthy cells. Their metabolism runs at full speed and
requires large amounts of micronutrients, particularly iron. However, high levels of iron in the
cell lead to the production of extremely harmful free radicals. To protect itself from these, the
cell inactivates free iron by binding it to what are called iron storage proteins.
Collaborating with physicians of the Dermatology Department of Mannheim University
Hospitals, Dr. Karsten Gülow and Professor Dr. Peter Krammer, head of the Division of
Immunogenetics at DKFZ, investigated Sézary's disease (also called Sézary syndrome), an
extremely aggressive type of cutaneous T cell lymphoma. The majority of currently available
treatments are not really effective against this fatal type of cancer.
Using a molecular-biological trick, Gülow and colleagues succeeded in blocking the
production of one of the iron storage proteins in lymphoma cells. This leads to a rise in the
level of free, non-bound iron in these cells. The iron boosts the production of free oxygen
radicals which cause oxidative stress and, thus, cause damage to the cancer cells and induce
their death. Healthy cells with their low iron level, however, survive the treatment unharmed.
The DKFZ researchers have already found evidence that this iron effect also works in other
lymphomas. They are now investigating whether selective release of iron may be a suitable
approach for developing a novel cancer treatment.
###
Michael K. Kiessling, Claus D. Klemke, Marcin M. Kamiński, Ioanna E. Galani, Peter H.
Krammer, and Karsten Gülow: Inhibition of constitutively activated NF-κB induces ROS- and
iron dependent cell death in cutaneous T cell lymphoma. Cancer Research 2009;
DOI:10.1158/0008-5472.CAN-08-3221
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is the
largest biomedical research institute in Germany and is a member of the Helmholtz
Association of National Research Centers. More than 2,000 staff members, including 850
scientists, are investigating the mechanisms of cancer and are working to identify cancer risk
factors. They provide the foundations for developing novel approaches in the prevention,
diagnosis, and treatment of cancer. In addition, the staff of the Cancer Information Service
(KID) offers information about the widespread disease of cancer for patients, their families,
and the general public. The Center is funded by the German Federal Ministry of Education and
Research (90%) and the State of Baden-Württemberg (10%).
3 月 11 日
Cell pathway on overdrive prevents cancer response to dietary
restriction
59
FINDINGS: Whitehead Institute researchers have pinpointed a cellular pathway that
determines whether cancerous tumors are susceptible to dietary restriction during their
development. When this pathway, known as PI3K is permanently turned "on" via mutation,
tumors grow and proliferate independent of the amount of food consumed. However, when
the PI3K pathway operates normally, tumors respond to dietary restriction—defined as food
consumption limited to 60% of normal--and become smaller in size.
RELEVANCE: Scientists have known about the correlation between dietary restriction and
tumor growth since the early 20th Century. These findings bring clarity to the
long-unanswered question of why certain tumors are unaffected by reduced caloric intake.
CAMBRIDGE, Mass. (March 11, 2009) – Whitehead Institute researchers have pinpointed a
cellular pathway that determines whether cancerous tumors respond to dietary restriction
during their development.
Studying human cancer cell lines in mice, researchers have found that when this pathway,
known as PI3K, is activated permanently via mutation, tumors grow and proliferate
independent of food consumption. However, when the PI3K pathway operates normally,
dietary restriction (defined as a 60% reduction in normal intake), results in smaller tumors.
The findings are published online in the March 11 issue of Nature.
"Our findings indicate that each tumor cell bears a signature that determines whether or not
that cell will be affected by dietary restriction," says Nada Kalaany, first author of the paper
and a postdoctoral researcher in the lab of Whitehead Member David Sabatini. "We think that
mutations in the PI3K pathway are a major determinant of the sensitivity of tumors to dietary
restriction."
The connection between food consumption and tumor growth is not new. In the early 20th
Century, scientists first noted the correlation between a restricted diet and decreased tumor
size and incidence. However, some cancers' growth rate was unaffected by a decrease in food
consumption. The reason for this difference remained unclear.
To determine how various tumor types are affected by dietary resistance, Kalaany injected
cells from human prostate, breast, brain, and colon cancers into mice in an experimental
protocol used frequently to study human cancers. The mice then ate as much as they liked
(control group) or received 60% of the caloric intake of their counterparts (the dietary
restriction (DR) group). Both groups ingested the same amounts of vitamins and minerals.
After a few weeks, Kalaany saw that the cancers could be divided into DR-sensitive tumors,
with significantly lower tumor volumes in the DR mice than in control mice, or DR-resistant
tumors, whose sizes were apparently unaffected by normal or restricted diets.
Kalaany then grew the same cancer cells in Petri dishes to see how the DR-sensitive and
DR-resistant cancers respond to food-related hormones in the body. The cancers were grown
solutions containing increasing amounts of insulin, insulin-like growth factor 1 (IGF1) or in a
solution without these hormones. The results supported the previous experiment: those
60
cancer cells that were DR-sensitive in the mice were also stunted by a lack of insulin and IGF1;
those cancer cells that were DR-resistant in the mice were unaffected by changes in insulin
and IGF1 levels.
Because the difference between the two groups was sensitivity or insensitivity to insulin and
IGF1, Kalaany thought the insensitive tumors may have something amiss in a cellular process
called the PI3K pathway, which is activated by insulin/IGF1. A search for mutations in two
genes found in the PI3K pathway that are often associated with cancer (PI3KCA and PTEN),
revealed that DR-resistant cells had mutations in one or the other of the genes, while
DR-sensitive cells showed no such mutations.
Using a DR-resistant tumor cell line in which the PTEN gene could be switched on or off,
Kalaany tested whether a change in the PTEN gene alone could affect a tumor's sensitivity to
DR. When the PTEN gene was turned off, the cancer cells were not affected by dietary
restriction, and tumor size increased similarly in control and DR mice. But when PTEN was
turned on, thereby restoring normal function to the PI3K pathway, the cells became
sensitized to dietary restriction and tumor size was smaller in the DR group.
This research was confirmed in two mouse models of cancer, one with prostate cancer caused
by PTEN deletion and one with lung cancer and a functioning PTEN gene. Again, the mice
without the PTEN gene did not respond to dietary restriction, but the mice with a functioning
PTEN gene were sensitive to dietary restriction.
Sabatini says that Kalaany's results could lead to cancer treatments tailored to the
characteristics of an individual patient's tumor cells.
"Her findings suggest that if we have therapies that mimic dietary restriction, we could better
predict which tumors would respond to those dietary restriction-mimicking drugs and which
ones would not," says Sabatini.
Sabatini is also intrigued by the inverse relationship between too much food and an increase
in tumors. "We already know that the United States has an epidemic of obesity and that
obesity is probably the biggest contributor to cancer in the U.S., even more so than smoking.
Does this research have anything to do with that correlation between obesity and cancer, that
if we make animals really obese, that this pathway is also involved in determining their
sensitivity to cancer? Answering that question is the next step."
3 月 11 日
Detecting Cancer, Diabetes Through Breath Or Urine Analysis
A future sensor may take away a patient's breath while simultaneously determining whether
the patient has breast cancer, lung cancer, diabetes or asthma. A University of Missouri
researcher is developing a device that will analyze breath or urine samples for volatile markers
inside the body that indicate disease. These volatile markers, such as alkanes, acetones or
nitric oxide, give doctors clues about what is happening inside the body and can be used as a
61
diagnostic tool.
"Little traces of certain gas molecules in the breath or urine tell us if anything unusual is going
on in the body," said Xudong "Sherman" Fan, investigator in the Christopher S. Bond Life
Sciences Center. "Measuring these volatile markers would be a non-invasive way to determine
if a disease is present without having to draw blood or complete a biopsy. In addition to the
biomarkers already discovered, many more potential volatile markers are still under
investigation."
The sensor device known as the opto-fluidic ring resonator (OFRR) is an optical gas sensor
that consists of a polymer-lined glass tube that guides the flow of a gas vapor and a ring
resonator that detects the molecules that pass through the glass tube. As the gas vapor enters
the device, molecules in the vapor separate and react to the polymer lining. Light makes
thousands of loops around the gas or liquid sample. The more the light loops around the
sample, the more the light energy interacts with the gas vapor. These repetitive interactions
enable the detection of vapor molecules down to a very small quantity.
Optical gas sensors have broad applications in the fields of industry, military, environment,
medical care and homeland security. In addition to OFRR's application in the medical industry,
the device also can improve the detection of explosives on the battlefield. Currently, the
existing gas vapor sensor technology is very bulky with equipment weighing more than 100
pounds and is difficult to use in the field.
"We hope to design a vapor sensor that has ultra-high sensitivity, specific and rapid response
to a certain molecule, as well as the ability of on-the-spot chemical analyses, which usually
requires the sensor to be small, portable, reusable and have less power consumption," said
Fan, who also is assistant professor of biological engineering in the MU College of Engineering
and the MU College of Agriculture, Food and Natural Resources. "If the gas sensor is portable,
military personnel can determine more quickly whether an area is dangerous."
Notes:
Fan's research is funded by the National Science Foundation and has been published in
peer-reviewed journals such as Optics Letters, Optics Express and Analytical Chemistry.
Source: Kelsey Jackson
3 月 11 日
Friendly Competition Among Area Dental Schools To Educate
About Oral Cancer
Mention cancer and most people think breast, lung, or prostate. But the less talked about oral
cancer kills nearly half of all people diagnosed with the disease in five years, largely because
patients do not recognize the symptoms.
62
That statistic got Courtney Brady, a second-year dental student at Boston University Goldman
School of Dental Medicine (BUGSDM), and first-year student Dee Gulis thinking about what
they could do to get the word out about oral cancer, and they think they found the answer.
Brady and Gulis are leading a team BUGSDM students, faculty, staff, and friends to walk Relay
for Life, a 12-hour walk/run event at Boston University Track and Tennis Center from 6 p.m.
April 18 to 6 a.m. April 19.
"Too often, oral cancer is pushed off to the side when people talk about cancer," Brady says.
"We want to make sure people know that oral cancer can be deadly and that they know the
symptoms. It is a disease people need to watch out for."
Brady has invited all other dental schools in the Northeast district 1 of the American Student
Dental Association (ASDA) to join BUGSDM. Now BUGSDM, Tufts, Harvard, and UConn are
vying to recruit the most team members.
"While raising money is important, our goal for this first year is seeing a lot of participation from
our school," Brady says. "We want everybody to get involved and see how great this event is
and for it to grow into a huge event for BUGSDM each year to come."
The BUGSDM team is adding a unique twist to the event-an oral cancer education
booth-which, to Brady and Gulis' knowledge, is the first of its kind at any Relay for Life event
nationwide. Walkers from the 100 teams planning to attend Relay for Life can learn about oral
cancer between laps around the track.
When not walking, participants will fill their time listening to local bands perform, playing
football inside the track lanes, camping out with friends and classmates, and visiting other
teams' booths to learn about the causes they support.
You do not need to be athletic to join, according to Gulis. "If you can walk, you can participate,"
she says.
Brady adds that in addition to supporting oral cancer awareness, attending Relay for Life is a
great way to kick off Marathon Monday, which follows the next day on April 20.
Anyone can support BUGSDM's Relay for Life team or join for just a $10 registration fee with
no obligation to raise more money. To learn more, visit http://www.relayforlife.org/BU
The mission of Boston University Goldman School of Dental Medicine is to provide excellent
education to dental professionals throughout their careers; to shape the future of dental
medicine and dental education through research; to offer excellent health care services to the
community; to participate in community activities; and to foster a respectful and supportive
environment.
63
3 月 11 日
New Biomarkers Could Help Clinicians Determine Whether Or Not
A Pancreatic Cyst Is Potentially Dangerous
A handful of proteins, detected in incredibly tiny amounts, may one day help doctors
distinguish between a harmless lesion in the pancreas and a potentially deadly one, say
researchers at Fox Chase Cancer Center.
The researchers believe that these protein biomarkers, if confirmed in subsequent studies,
could represent reliable indicators of pancreatic cancer or precancerous pancreatic lesions,
which would allow for earlier, perhaps more successful, treatment. Their findings appear in the
March issue of the journal Pancreas, available online now.
"New technologies have become very good at identifying pancreatic cysts when they appear,
but we know very little about how to categorize these cysts," says the study's senior author
Anthony Yeung, Ph.D., molecular biologist and member of Fox Chase's faculty. "We can detect,
in as little as 40 microliters of cyst fluids a group of proteins that might collectively be used as
indicators of a potentially cancerous cyst."
The difficulty of detecting pancreatic cancer early is one of the reasons that the disease
remains one of the deadliest forms of cancer. In some cases, pancreatic cancer develops
within small pancreatic cysts that are originally benign, but become cancerous over time. As
high-resolution imaging techniques, such as magnetic resonance imaging (MRI), are used
more often in clinical medicine, doctors are finding many more small, fluid-filled cystic lesions
of the pancreas.
"Many of these cysts are completely benign and have little or no risk of becoming cancerous.
However, a subset of pancreatic cysts carry a real risk of becoming malignant over time," says
co-author Jeffrey Tokar, M.D., Fox Chase gastroenterologist. "Many patients with pancreatic
cysts are referred to us for endoscopic needle aspiration of fluid within the cyst, which is then
sent to the laboratory and a variety of tests are commonly performed. However, while these
tests can be useful, it often remains impossible to tell a patient their absolute risk of
progression to cancer."
According to Tokar, there are currently two main options for doctors once they find a pancreatic
cyst, and neither is ideal. One option is to advise the patient to have major surgery to remove
the portion of the pancreas that contains the cyst, in hopes of eliminating the chance that it will
develop into cancer. Unfortunately, with this approach, some patients will be subjected to the
risks of surgery for a cyst that was never going to cause them any problems. The other option
is to take a "watch-and-wait" approach, which can become costly, expose patients to additional
radiation (i.e., if computerized tomography, or CT scans, are used), and may not always detect
cancers within cysts at its earliest stages. "What we need are methods to identify benign cysts
that do not have significant cancer risk, so that we can concentrate on the cysts that have the
greatest risk of malignancy," Tokar says.
64
Using an endoscopic ultrasound-guided technique, Tokar and his colleagues collected fluid
from the cysts of 20 research participants with a small needle. Yeung and his laboratory team
then assayed the fluid to determine the number and type of proteins it contained. Identifying
the proteins took more than eight months of continuous time with a mass spectrometer, an
instrument that can determine the makeup of - and thereby identify - individual molecules.
Among the proteins they found were members of three families of proteins previously
proposed to be biomarkers for pancreatic cancer, called mucins, CEACAMs, and S100s.
"From these samples we've identified a panel of these proteins that could all be considered
harbingers of cancer in some way," Yeung says. "Now that we know what we are looking for,
we can use even more powerful spectrometry techniques to find this pattern of proteins fast
enough that it could be used as part of a clinical service."
The researchers are looking to expand their study and to follow patients over a longer period of
time to see how well this biomarker profile predicts the likelihood that a pancreatic lesion
already contains or may develop into pancreatic cancer, but they will need to recruit more
patients. Fortunately, it helps that they can do more with less, as their technique can find
biomarkers amid very small amounts of fluid obtained from small pancreatic lesions that are
less than one centimeter (0.39 inches) in size.
"We are in great need for powerful tests, such as the ones that Dr. Yeung performs, which
require only a tiny volume of fluid but can provide a tremendous amount of useful information,"
says Tokar. "We will need to work with colleagues at multiple medical centers to continue
studying this promising technique for evaluating pancreatic cyst fluid, in hopes of building
enough evidence to make it a routine part of patient care."
Notes:
Funding for this research comes from grants from the National Cancer Institute and the Byrne
Foundation.
Source: Greg Lester
3 月 11 日
Immune Based Drug Approved In Europe For Pediatric Cancer
Patients
The European Commission, which oversees legislation and regulation for the European Union,
has approved a therapy for pediatric patients with non-metastatic, resectable osteosarcoma, a
type of bone cancer. The approval is based on clinical studies led by researchers at The
University of Texas M. D. Anderson Cancer Center and a national co-operative group.
MEPACT (mifamurtide, L-MTP-PE) is an immune-based therapy, that when combined with
chemotherapy, resulted in approximately a 30 percent decrease in the risk of death with 78
percent of patients surviving more than six years following treatment. This therapy is the first in
65
more than 20 years to improve the long-term survival of osteosarcoma patients.
Eugenie Kleinerman, M.D., head of the Children's Cancer Hospital at M. D. Anderson Cancer
Center, was the first investigator to translate the drug from preclinical testing to a Phase I
clinical trial in humans. She also led the Phase II clinical trial for pediatric patients with
relapsed osteosarcoma, which was followed by a Children's Oncology Group Phase III trial for
newly diagnosed patients.
Kleinerman originally proposed the use of this immune therapy for osteosarcoma after Isaiah J.
Fidler, D.V.M., Ph.D., professor in M. D. Anderson's Department of Cancer Biology and
director of the Center for Metastasis Research, demonstrated that MEPACT induced the
regression of melanoma lung metastases in mice.
"When he showed that MEPACT caused the macrophages in the lung to kill tumor cells, I
decided that the drug may have therapeutic potential in patients with osteosarcoma, which
most often metastasizes to the lungs," says Kleinerman. "From my own preclinical research,
we were able to show how MEPACT stimulated human immune cells to react against
osteosarcoma cells."
MEPACT works by stimulating certain white blood cells, called macrophages, to kill tumor cells.
The drug is shaped in a sphere, also known as a vesical, made up of lipids. Inside the vesical
is muramyl tripeptide (MTP). The lipids trigger the macrophages to consume MEPACT. Once
consumed, the MTP stimulates macrophages, particularly in the liver, spleen and lungs, to find
tumor cells and kill them.
Patients undergo pre-operative chemotherapy followed by surgery to resect the bone tumor
and then receive post-operative chemotherapy. While receiving post-operative chemotherapy,
patients also are given the immune therapy intravenously twice a week for three months and
then once a week for six months. The chemotherapy acts like a bomb sent in to destroy the
tumor, while MEPACT acts as a special forces unit sent in to clean out any remaining pockets
of microscopic disease.
"Relapsed osteosarcoma is often resistant to chemotherapy," says Kleinerman. "By giving
MEPACT to newly diagnosed patients, we hope to prevent relapse by taking care of any
remaining tumor cells after chemotherapy."
Currently, only relapsed pediatric patients with osteosarcoma are able to receive treatment
with MEPACT through compassionate use in the United States. MEPACT was granted orphan
drug status in the United States in 2001 but has not been approved by the Food and Drug
Administration for use in newly diagnosed patients. Orphan drug status is given to therapeutic
agents that target rare diseases as an incentive for pharmaceutical companies to manufacture
these agents.
"We have been working with this therapy for more than two decades, so getting approval in
66
Europe is a huge milestone for those of us fighting pediatric cancer," says Kleinerman. "This
drug has made significant strides for long-term survival of children with osteosarcoma."
About M. D. Anderson
The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's
most respected centers focused on cancer patient care, research, education and prevention.
M. D. Anderson is one of only 40 comprehensive cancer centers designated by the National
Cancer Institute. For four of the past six years, including 2008, M. D. Anderson has ranked No.
1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News &
World Report.
About the Children's Cancer Hospital at M. D. Anderson
The Children's Cancer Hospital at The University of Texas M. D. Anderson Cancer Center has
been serving children, adolescents and young adults for more than 50 years. In addition to the
groundbreaking research and quality of treatment available to pediatric patients, the Children's
Cancer Hospital provides its patients with comprehensive programs that help children lead
more normal lives during and after treatment. For further information, visit the Children's
Cancer Hospital Web site at http://www.mdanderson.org/children.
University of Texas M. D. Anderson Cancer Center
1515 Holcombe Blvd., Box 229
Houston
TX 77030
United States
3 月 12 日
A new measure for the malignancy of melanoma
Every tumor, starting from a size of a few millimeters, depends on a supply of nutrients and
oxygen. Therefore, using special growth factors, it induces vascular wall cells of neighboring
blood vessels to sprout new capillaries in order to get connected to the blood circulation.
This process called angiogenesis involves a number of different growth factors and their
respective receptors on the vascular wall cells. The departments of Prof. Dr. Hellmut Augustin
and Prof. Dirk Schadendorf of DKFZ and Mannheim Medical Faculty of the University of
Heidelberg have investigated the role of a growth factor called angiopoietin-2 (Ang2) in
malignant melanoma. The docking station of Ang2 is the receptor Tie2 on the surface of
endothelial cells, which form the inner lining of blood vessels. Together with other signaling
molecules, Ang2 induces sprouting of endothelial cells and the formation of new capillaries.
When measuring the Ang2 concentrations in blood samples of melanoma patients, the
investigators discovered that larger tumors and more advanced disease stages correlate with
67
high levels of Ang2. If one tracks the Ang2 levels of individual patients over time, a rise
parallel to disease progression can be observed. In contrast, patients who have lived with the
disease for a long time, i.e., whose disease is not or only slightly progressive, have lower
Ang2 levels. The scientists found out that Ang2 concentration in blood serum is a more
precise indicator of the progression and stage of the disease than previously used
biomarkers.
This close association between melanoma progression and Ang2 level prompted the question
of whether the Ang2 growth factor really only stimulates vascularization in the tumor or
whether it has additional influence on the properties of the cancer cells themselves. Such an
effect had not yet been proposed for any one of the various growth factors which act on the
cells of the vascular walls. Melanoma cells were really found to produce both soluble Ang2
and the matching receptor, Tie2, on their own cell membrane. As a result, they are
theoretically capable of activating themselves. In order to check this, researchers switched
off the Ang2 production in melanoma cells using a genetic trick. Test systems in the culture
dish subsequently revealed that the skin cancer cells had lost their ability to migrate. The
migration tendency of cancer cells is regarded as important information about their ability to
invade other tissue in the body and metastasize.
The tumor appears to seize the signaling system of vascularization and, thus, to strengthen
its malignant properties. "Ang2 is a very promising candidate," Hellmut Augustin comments
on the results, „both as a biomarker for better monitoring of disease progression and as a
target structure for therapy measures." Blocking Ang2 might not only attack the tumor's
blood supply, but also reduce its malignant growth.
###
Iris Helfrich, Lutz Edler, Antje Sucker, Markus Thomas, Sven Christian, Dirk Schadendorf and
Hellmut G. Augustin: Angiopoietin-2 Levels Are Associated with Disease Progression in
Metastatic Malignant Melanoma. Clinical Cancer Research 2009; 2009,
DOI:10.1158/1078-0432.CCR-08-1615
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is the
largest biomedical research institute in Germany and is a member of the Helmholtz
Association of National Research Centers. More than 2,000 staff members, including 850
scientists, are investigating the mechanisms of cancer and are working to identify cancer risk
factors. They provide the foundations for developing novel approaches in the prevention,
diagnosis, and treatment of cancer. In addition, the staff of the Cancer Information Service
(KID) offers information about the widespread disease of cancer for patients, their families,
and the general public. The Center is funded by the German Federal Ministry of Education and
Research (90%) and the State of Baden-Württemberg (10%).
3 月 12 日
68
Cell Path Overdrive Prevents Cancer Response To Diet
Restriction
Whitehead Institute researchers have pinpointed a cellular pathway that determines whether
cancerous tumors respond to dietary restriction during their development.
Studying human cancer cell lines in mice, researchers have found that when this pathway,
known as PI3K, is activated permanently via mutation, tumors grow and proliferate
independent of food consumption. However, when the PI3K pathway operates normally,
dietary restriction (defined as a 60% reduction in normal intake), results in smaller tumors. The
findings are published online in the March 11 issue of Nature.
"Our findings indicate that each tumor cell bears a signature that determines whether or not
that cell will be affected by dietary restriction," says Nada Kalaany, first author of the paper and
a postdoctoral researcher in the lab of Whitehead Member David Sabatini. "We think that
mutations in the PI3K pathway are a major determinant of the sensitivity of tumors to dietary
restriction."
The connection between food consumption and tumor growth is not new. In the early 20th
Century, scientists first noted the correlation between a restricted diet and decreased tumor
size and incidence. However, some cancers' growth rate was unaffected by a decrease in food
consumption. The reason for this difference remained unclear.
To determine how various tumor types are affected by dietary resistance, Kalaany injected
cells from human prostate, breast, brain, and colon cancers into mice in an experimental
protocol used frequently to study human cancers. The mice then ate as much as they liked
(control group) or received 60% of the caloric intake of their counterparts (the dietary restriction
(DR) group). Both groups ingested the same amounts of vitamins and minerals. After a few
weeks, Kalaany saw that the cancers could be divided into DR-sensitive tumors, with
significantly lower tumor volumes in the DR mice than in control mice, or DR-resistant tumors,
whose sizes were apparently unaffected by normal or restricted diets.
Kalaany then grew the same cancer cells in Petri dishes to see how the DR-sensitive and
DR-resistant cancers respond to food-related hormones in the body. The cancers were grown
solutions containing increasing amounts of insulin, insulin-like growth factor 1 (IGF1) or in a
solution without these hormones. The results supported the previous experiment: those cancer
cells that were DR-sensitive in the mice were also stunted by a lack of insulin and IGF1; those
cancer cells that were DR-resistant in the mice were unaffected by changes in insulin and
IGF1 levels.
Because the difference between the two groups was sensitivity or insensitivity to insulin and
IGF1, Kalaany thought the insensitive tumors may have something amiss in a cellular process
called the PI3K pathway, which is activated by insulin/IGF1. A search for mutations in two
69
genes found in the PI3K pathway that are often associated with cancer (PI3KCA and PTEN),
revealed that DR-resistant cells had mutations in one or the other of the genes, while
DR-sensitive cells showed no such mutations.
Using a DR-resistant tumor cell line in which the PTEN gene could be switched on or off,
Kalaany tested whether a change in the PTEN gene alone could affect a tumor's sensitivity to
DR. When the PTEN gene was turned off, the cancer cells were not affected by dietary
restriction, and tumor size increased similarly in control and DR mice. But when PTEN was
turned on, thereby restoring normal function to the PI3K pathway, the cells became sensitized
to dietary restriction and tumor size was smaller in the DR group.
This research was confirmed in two mouse models of cancer, one with prostate cancer caused
by PTEN deletion and one with lung cancer and a functioning PTEN gene. Again, the mice
without the PTEN gene did not respond to dietary restriction, but the mice with a functioning
PTEN gene were sensitive to dietary restriction.
Sabatini says that Kalaany's results could lead to cancer treatments tailored to the
characteristics of an individual patient's tumor cells.
"Her findings suggest that if we have therapies that mimic dietary restriction, we could better
predict which tumors would respond to those dietary restriction-mimicking drugs and which
ones would not," says Sabatini.
Sabatini is also intrigued by the inverse relationship between too much food and an increase in
tumors. "We already know that the United States has an epidemic of obesity and that obesity is
probably the biggest contributor to cancer in the U.S., even more so than smoking. Does this
research have anything to do with that correlation between obesity and cancer, that if we make
animals really obese, that this pathway is also involved in determining their sensitivity to
cancer? Answering that question is the next step."
David Sabatini's primary affiliation is with Whitehead Institute for Biomedical Research, where
his laboratory is located and all his research is conducted. He is also a Howard Hughes
Medical Institute investigator and a professor of biology at Massachusetts Institute of
Technology.
Full Citation:
"Tumours with PI3K activation are resistant to dietary restriction"
Nature, online March 11, 2009
Nada Y. Kalaany (1,2,3) & David M. Sabatini (1,2,3,4)
1. Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge,
70
Massachusetts 02142, USA.
2. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of
Technology, Cambridge, Massachusetts 02139, USA.
3. Koch Institute for Integrative Cancer Research at MIT, 77 Massachusetts Avenue,
Cambridge, Massachusetts 02139, USA.
4. Broad Institute, Seven Cambridge Center, Cambridge, Massachusetts 02142, USA.
Whitehead Institute for Biomedical Research
9 Cambridge Center, Rm. 201
Cambridge
MA 02142
United States
3 月 12 日
Iron Induces Death In Tumor Cells
Rapid growth of cancer cells and their frequent divisions have their price: Cancer cells need
considerably more energy than healthy cells. Their metabolism runs at full speed and requires
large amounts of micronutrients, particularly iron. However, high levels of iron in the cell lead to
the production of extremely harmful free radicals. To protect itself from these, the cell
inactivates free iron by binding it to what are called iron storage proteins.
Collaborating with physicians of the Dermatology Department of Mannheim University
Hospitals, Dr. Karsten Gülow and Professor Dr. Peter Krammer, head of the Division of
Immunogenetics at DKFZ, investigated Sézary's disease (also called Sézary syndrome), an
extremely aggressive type of cutaneous T cell lymphoma. The majority of currently available
treatments are not really effective against this fatal type of cancer.
Using a molecular-biological trick, Gülow and colleagues succeeded in blocking the production
of one of the iron storage proteins in lymphoma cells. This leads to a rise in the level of free,
non-bound iron in these cells. The iron boosts the production of free oxygen radicals which
cause oxidative stress and, thus, cause damage to the cancer cells and induce their death.
Healthy cells with their low iron level, however, survive the treatment unharmed.
The DKFZ researchers have already found evidence that this iron effect also works in other
lymphomas. They are now investigating whether selective release of iron may be a suitable
approach for developing a novel cancer treatment.
Notes:
Michael K. Kiessling, Claus D. Klemke, Marcin M. Kamiński, Ioanna E. Galani, Peter H.
71
Krammer, and Karsten Gülow: Inhibition of constitutively activated NF-κB induces ROS- and
iron dependent cell death in cutaneous T cell lymphoma. Cancer Research 2009;
DOI:10.1158/0008-5472.CAN-08-3221
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is the
largest biomedical research institute in Germany and is a member of the Helmholtz
Association of National Research Centers. More than 2,000 staff members, including 850
scientists, are investigating the mechanisms of cancer and are working to identify cancer risk
factors. They provide the foundations for developing novel approaches in the prevention,
diagnosis, and treatment of cancer. In addition, the staff of the Cancer Information Service
(KID) offers information about the widespread disease of cancer for patients, their families, and
the general public. The Center is funded by the German Federal Ministry of Education and
Research (90%) and the State of Baden-Württemberg (10%).
Source: Dr. Sibylle Kohlstädt
3 月 12 日
Utility Of Circulating DNA As Novel Diagnostics For Human Cancer,
Mad Cow Disease And Other Conditions
Chronix Biomedical - developing and applying proprietary techniques to detect and analyze
circulating nucleic acid sequences for the diagnosis and management of disease - reported
that three recent studies published in peer-reviewed journals have further confirmed the
potential diagnostic and prognostic utility of fragments of DNA and RNA that circulate in the
blood, known as circulating nucleic acids (CNAs). Data from these studies confirm previous
findings showing that CNAs can identify the presence of certain diseases in blood samples
months to years before clinical symptoms appear.
"The recent publication of these three studies represents a major milestone in the recognition
of CNAs as novel diagnostic tools," said Howard Urnovitz, Ph.D., CEO of Chronix. "Our ability
to accurately identify and characterize the presence of significant differences in CNA levels
and sequences between healthy and diseased individuals demonstrates how CNAs would be
used for diagnosis and disease management in conditions as diverse as bovine spongiform
encephalopathy (mad cow disease) and human cancers."
In the study appearing in the current online edition of Clinical Chemistry, scientists from
Chronix applied ultra-high speed sequencing technology and proprietary data analysis tools to
characterize and categorize the CNA markers present in multiple individuals. The resulting
databases of CNAs associated with specific disease states can be used to identify persons
with undiagnosed disease, and potentially, to track changes in disease status. For example,
the study found that one of the presumed healthy volunteers was actually infected with
hepatitis B.
This study follows publication in January of research from scientists at the University of
72
Calgary, Canada, the University of Göttingen, Germany and Chronix showing the ability of a
simple blood test based on circulating DNA sequences to identify the presence of bovine
spongiform encephalopathy (BSE) and the related condition chronic wasting disease (CWD) in
live animals long before symptoms were evident. This advance is especially significant since
BSE can now only be confirmed by examining the brain tissue of dead animals. Following
expected confirmation in larger studies, this new approach could revolutionize testing for BSE,
making it economically and logistically feasible to screen all cattle in the food chain before BSE
symptoms appear. The study was published in the journal Nucleic Acids Research.
A third reported study highlights the potential utility of CNAs in the management of cancer. Dr.
Urnovitz, and Brian G.M. Durie, M.D., Medical Director and co-founder of the International
Myeloma Foundation, identified specific DNA sequences circulating in the blood of a patient
with the bone marrow cancer multiple myeloma and tracked variations in these sequences as
the patient's myeloma moved in and out of remission. There was also an unexpected finding
when CNAs identified the development of a secondary cancer in this patient, before it was
clinically apparent. This preliminary study is significant because it shows that CNAs can
potentially be used to diagnose, monitor and manage cancer treatment. The abstract reporting
this data was published in the journal Blood in connection with the December 2008 meeting of
the American Society of Hematology.
"This approach opens the door to a new tool that will enable us to follow the progress of cancer
treatment and give us an early warning when a myeloma patient is about to come out of
remission," said Dr. Durie. "This will allow us to stay ahead of the disease instead of waiting for
the patient to get sick before we can act. That capability will represent a major change in the
way we treat this cancer."
Dr. Urnovitz concluded, "Even in these experiments we found unexpected results undiagnosed hepatitis in one patient and a secondary cancer in another - confirming the utility
of CNAs in finding unsuspected disease. With these multiple proof-of-concept experiments
now completed, we are embarking on the studies needed to further confirm and commercialize
this powerful new approach with important applications in personalized medicine and human
health."
Chronix intends to work with a number of industry partners to develop and commercialize its
CNA technology for diagnostic and prognostic applications. These emerging markets for novel
genetic-based assays have multi-billion dollar potential. Because the Chronix technology can
identify early changes in disease status, it also can be used to generate surrogate measures
for drug development studies aimed at distinguishing responder and non-responder patient
subgroups. The company has recently initiated discussions with potential pharmaceutical
partners.
About Chronix Biomedical
Chronix Biomedical is pioneering a breakthrough approach to the diagnosis and management
73
of chronic diseases and cancer. It has developed proprietary technology that measures and
categorizes circulating nucleic acids, DNA sequences circulating in the blood that are
associated with specific changes in disease and health status. Using advanced genome
analysis methods, proprietary data tools and disease-specific databases, Chronix has
demonstrated the utility of its diagnostic and prognostic approach in mad cow disease and
multiple myeloma, and studies in other diseases are underway. The company plans to
collaborate with a variety of partners to develop and market its DNA-based assays that have
the potential to transform the management of a broad range of cancers and other conditions.
Chronix is headquartered in San Jose, California and has research facilities in Germany.
3 月 12 日
News From The Journal Of The National Cancer Institute, March 10,
2009
Herpesvirus 8 K1 Oncoprotein Directly Inhibits Fas-Mediated Cell Death
Human herpesvirus 8 (HHV-8) K1 oncoprotein binds directly to the Fas protein in tissue culture
cells and blocks Fas-mediated cell death.
HHV-8 is associated with Kaposi sarcoma in humans and expression of the HHV-8 K1
oncoprotein leads to lymphoma in transgenic mice. Previous work suggested that K1 inhibits
Fas-mediated cell death but the exact mechanism was unknown.
In the current study, Felipe Samaniego, M.D., of the University of Texas M. D. Anderson
Cancer Center in Houston, and colleagues transfected human cell lines with either a wild-type
K1 gene or a K1 gene lacking an Ig domain, which is often involved in protein-protein
interactions.
Fas activity was inhibited in cells that expressed wild-type K1 but not in cells expressing the
Ig-deleted K1 mutant. Wild-type K1 protein expression protected mice from death due to
stimulation of the Fas receptor, but the Ig-deleted mutant protein did not.
"The current results show that the HHV-8 protein K1 physically associates with Fas and
thereby dis¬rupts initiation of Fas-mediated apoptotic signaling induced by agonistic
antibodies and [Fas ligand]," the authors conclude.
Contact: Scott Merville
Silencing HPV Genes Induces Cell Death in Oropharyngeal Cancer Cell Lines
Repression of human papillomavirus type 16 (HPV16) oncogenes E6 and E7 led to restoration
of tumor suppressor gene activity and induced programmed cell death in oropharyngeal
cancer cells grown in culture.
74
HPV16 is known to cause cervical cancer and has been associated with oropharyngeal
cancers. However, mechanistic data showing a causal relationship between HPV16 and head
and neck cancers has been lacking.
In the current study, Amanda Psyrri, Ph.D., of Yale University School of Medicine in New
Haven, Conn., and colleagues introduced short hairpin RNAs (shRNAs) into HPV16-positive
oropharyngeal cell lines. The shRNAs were designed either to interfere with HPV oncogenes
E6 and E7 or to encode a scrambled control sequence.
Inhibition of the viral oncogenes resulted in renewed expression of endogenous tumor
suppressor proteins p53 and pRB. Apoptosis increased in two oropharyngeal cancer cell lines
from less than 13 percent in cells expressing the control shRNA to more than 70 percent in
cells expressing the E6/E7-inhibiting shRNAs.
"These results, along with epidemiological and molecular pathology studies, con¬tribute to the
establishment of a causal association between HPV and oropharyngeal cancer," the authors
write.
Contact: Renee Gaudette
ABO Blood Groups May Affect Pancreatic Cancer Risk
Individuals with blood type O appear to have a lower risk of pancreatic cancer than individuals
with blood types A, B, or AB, according to an analysis of two large independent cohort studies.
Genetic risk factors for sporadic pancreatic cancer are largely unknown. Previous studies have
suggested that ABO blood types may be associated with several different malignancies,
including pancreatic cancer.
In the current study, Brian Wolpin, M.D., of the Dana-Farber Cancer Institute in Boston, and
colleagues examined the association between blood type and pancreatic cancer incidence in
107,503 individuals who participated in either the Nurses' Health Study or the Health
Professional Follow-Up Study.
The age-adjusted incidence rate for participants with blood type O was 27 per 100,000
person-years, compared with 36 for individuals with blood type A, 41 for individuals with blood
type AB, and 46 for individuals with blood type B.
"In two large, independent prospective cohorts, we observed a sta¬tistically significantly
elevated risk for incident pancreatic cancer among participants with blood group antigens A or
B compared with those with blood group O," the authors write. "Additional investigation is
necessary to further confirm these findings and to determine the potential mechanisms by
which ABO antigens may influence pancreatic cancer risk."
75
Contact: Bill Schaller
Also in the JNCI:
In Postmenopausal Women Systematic Estimation Of Breast Cancer Risk Appears Justified
Study Methods Influence Estimates Of Lead Time And Overdiagnosis In Prostate Cancer
Notes:
The Journal of the National Cancer Institute is published by Oxford University Press and is not
affiliated with the National Cancer Institute. Visit the Journal online at
http://jnci.oxfordjournals.org/.
Source: Caroline McNeil
3 月 13 日
ARIMIDEX Offers Women Greater Protection Against HR+ Early
Breast Cancer Returning In The 1st 2 Yrs
"Anastrozole is the only aromatase inhibitor (AI) which has now been shown to prevent
recurrences in women with hormone receptor positive early breast cancer both during the
initial high-risk two years after surgery, and also well beyond the completion of treatment. In
breast cancer there are no guarantees and we can't predict which women will experience a
recurrence or when, so it is essential we have a treatment that has sustained efficacy against
all types of recurrence that persists even after treatment is completed. If we can stop breast
cancer returning, we can stop women dying from it." - Professor Tony Howell, Christie Hospital,
UK
Macclesfield, UK, Friday 13 March 2009: A new analysis of the ATAC (ARIMIDEX, Tamoxifen,
Alone or in Combination) trial, presented today at the 11th International St Gallen Oncology
Conference, Switzerland, shows that during the first two years after surgery, anastrozole is
superior to tamoxifen at reducing the risk of breast cancer returning in postmenopausal
women with hormone receptor positive early breast cancer (n=5,216).1 Anastrozole has
consistently demonstrated superiority over tamoxifen, both during the five-year treatment
period and beyond treatment completion.2 This latest analysis provides further reassurance
that prescribing anastrozole from the start protects women in the crucial first two years when
the risk of recurrence is highest, meaning that fewer patients have to be told the devastating
news that their breast cancer has returned.
When breast cancer returns, particularly outside the breast at distant sites such as bone, liver
or lung, it is no longer curable. Therefore protecting women from recurrence is the number one
priority for doctors and is imperative to saving lives. Although the risk of recurrence can persist
for up to at least 15 years,3 the risk is at its greatest within the first two years following surgery,
76
as seen in the ATAC study where over half of all excess recurrences and deaths among
patients taking tamoxifen occurred in the first two and a half years.2
This latest analysis confirms that in women who benefit from treatment with AIs (84% of the
total ATAC population) anastrozole is even more effective at preventing all types of early
recurrence (32%; 2 years post surgery) than previously seen in the broader study population
(17%; 2.5 years post surgery).1
Professor Howell continued, "It is now standard practice to assess the hormone receptor
status of breast tumours to guide the best course of treatment. ATAC is a ground breaking
study which has led to a significant change in treatment strategies in breast cancer with
aromatase inhibitors, such as anastrozole, now replacing tamoxifen as the standard of care for
postmenopausal women with hormone receptor positive disease in many countries. These
new findings confirm that in the women who receive it in routine clinical practice, anastrozole
offers reassuring protection against their cancer returning at the time of greatest risk, giving
women the best chance of continuing their lives cancer-free."
The ATAC trial is one of the world's largest and longest-running clinical studies in
postmenopausal women with early breast cancer. With a median follow-up of 100 months significantly longer than any other adjuvant AI trial - ATAC provides further information on the
safety profile of anastrozole which remains predictable, with no long-term safety concerns. As
a result of the weight of efficacy and safety evidence for anastrozole, it is now the most widely
prescribed AI worldwide, with over twice as many prescriptions as the next most widely
prescribed AI and over 4 million patient years' experience.4 These new data will offer doctors
treating hormone receptor positive postmenopausal early breast cancer further confidence that
initial treatment with anastrozole offers women the best chance of staying recurrence free.
Anastrozole offers sustained protection against recurrence, demonstrating significantly
superior disease free survival, time to recurrence, time to distant metastases and reduced
incidence of contralateral breast cancer compared with tamoxifen - a benefit which increases
over time and persists even after treatment ends.2
In ATAC, there were fewer recurrences in women with hormone receptor positive breast
cancer treated with anastrozole (n= 2,618) than tamoxifen (n=2,598) at 2, 5 and 9 years
post-surgery (91 vs 133; 245 vs 312; 385 vs 488 respectively).1
At a median follow-up of 2 years, compared to tamoxifen, anastrozole:1
- reduces the risk of all recurrences by 32% (HR 0.68 [0.52-0.88])
- reduces the risk of distant metastases by 21% (HR 0.79 [0.58-1.07])
- reduces the incidence of contralateral breast cancer by 78%.
ATAC Trial
77
The ARIMIDEX, Tamoxifen, Alone or in Combination (ATAC) trial is one of the world's largest
and longest-running clinical studies in postmenopausal women with early breast cancer. ATAC
is designed to investigate the comparative efficacy and tolerability of two adjuvant therapies:
ARIMIDEX (anastrozole) and tamoxifen.
This analysis of ATAC reinforces the significant superiority of ARIMIDEX over tamoxifen at
reducing the risk of breast cancer returning (also known as 'recurrence') in postmenopausal
women with hormone receptor positive early disease.1 The ATAC data also show that, even
approximately four years after treatment completion, the absolute reduction in the risk of
disease recurrence continues to increase with ARIMIDEX compared with tamoxifen.2
AstraZeneca
AstraZeneca is a major international healthcare business engaged in the research,
development, manufacture and marketing of prescription pharmaceuticals and the supply of
healthcare services. It is one of the world's leading pharmaceutical companies with healthcare
sales of $26.47 billion and leading positions in sales of gastrointestinal, cardiovascular,
neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow
Jones Sustainability Index (Global) as well as the FTSE4 Good Index.
http://www.astrazeneca.com
ARIMIDEX (anastrozole) is a trademark, the property of the AstraZeneca group of companies.
References
1. Howell A, Forbes J, Cuzick J et al. Initial adjuvant therapy with anastrozole - early and late
event data from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial in the
hormone-responsive population. St Gallen 2009 Poster
2. Saphner T, Tormey DC, Gray R. Annual hazard rates of recurrence for breast cancer after
primary therapy. J Clin Oncol 1996; 14(10): 2738-46
3. ATAC Trialists' Group. Effect of anastrozole and tamoxifen as adjuvant treatment for
early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol 2008; 9: 45-53
4. AstraZeneca IMS data on file
AstraZeneca
View drug information on Arimidex.
3 月 13 日
Women With Early Breast Cancer To Receive The Most Up-to-date
Information Available, Australia
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National Breast and Ovarian Cancer Centre (NBOCC) has now released the eagerly
anticipated revised version of its Guide for women with early breast cancer. The
comprehensive, 200 page resource provides information to support women with early breast
cancer* in making decisions about their treatment and care, as well as advice for family and
friends. The Guide walks women through every step of their breast cancer journey and is
broken down into five key areas: Breast cancer: the facts, Making sense of test results,
Treatment, When treatment is over, and Finding support.
"This resource compiles all the information a woman with early breast cancer will need in order
to understand her diagnosis, treatment and follow-up care," said Dr Helen Zorbas, CEO,
National Breast and Ovarian Cancer Centre.
Based on NBOCC's Clinical practice guidelines for the management of early breast cancer, the
consumer guide incorporates the latest evidence in a new, user-friendly, spiral bound format.
First released in 2003, the Guide is one of NBOCC's flagship resources, provided free of
charge to women at diagnosis to assist their understanding and decision-making. It has been
in consistently high demand with over 110,000 copies disseminated since its first release.
"The Guide provides women with reliable, up-to-date and easy to understand information in a
compact booklet that they can take with them as they go through their treatment," said Dr
Zorbas.
To download or order copies of the Guide for women with early breast cancer, visit NBOCC's
website http://www.nbocc.org.au. Orders can also be taken over the phone on 1800 624 973.
* Early breast cancer is cancer that is contained in the breast and may or may not have spread
to lymph nodes in the breast or armpit.
National Breast and Ovarian Cancer Centre is funded by the Australian Government and
works with consumers, health professionals, cancer organisations, researchers and
governments to improve care and cancer control in breast and ovarian cancer.
3 月 13 日
New Data On Link Between Cancer And Nutrition Discussed At
European Symposium
European experts in cancer and nutrition are meeting in Zurich, Switzerland late this month to
discuss cutting-edge research in one of the most important and fiercely debated topics in
cancer prevention: the link between diet and cancer.
There is growing evidence that many cancers may be prevented through healthy lifestyle,
including a nutritionally balanced diet. In addition, nutritional problems can also have a
negative impact on cancer management and the lives of patients.
The latest research findings on these topics will be discussed at the ESMO Symposium on
Cancer and Nutrition (20-21 March 2009), organized by the European Society for Medical
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Oncology incollaboration with the European Society for Clinical Nutrition and Metabolism
(ESPEN) and the Multinational Association of Supportive Care in Cancer (MASCC).
"Nutrition plays an important role in every stage of our fight against cancer, from prevention to
treatment and alleviation of the disease," said Dr Florian Strasser from the Oncological
Palliative Medicine department at the Kantonsspital St. Gallen, co-chair of the Symposium's
scientific committee. "But it is vital that the advice given to people is based on proper scientific
evidence."
The ESMO Symposium will discuss the latest evidence on the link between diet and cancer,
the impact of cancer on nutritional issues, in staging and alleviating cachexia. It will also
provide medical oncologists, dieticians, palliative care specialists, home care providers and
nurses with valuable information on how to properly consider nutritional issues in cancer
management.
"An inappropriate diet and physical inactivity are important risk factors for some cancers," said
Dr Andreas Ullrich, WHO Medical Officer for cancer control. Dr Ullrich will give a welcome
speech to symposium participants during which he will explain that the WHO Global Strategy
on Diet and Physical Activity provides a comprehensive set of policy recommendations to
promote healthy diets and physical activity. These policy options range from mass media
campaigns to educate people to fiscal and regulatory policies to influence agriculture, the food
industry and urban design.
Presentations at the meeting will include how the traditional Mediterranean diet can help
reduce cancer risk, nutritional advice to breast cancer survivors, and the role of nutrition and
exercise in managing fatigue, a major problem experienced by cancer patients.
Other presentations will include new data on topics such as:
- Childhood nutrition and later breast cancer risk
- The anti-tumour effects of green tea
- Malnutrition and patient distress in cancer
- Possible anti-tumour effects of soy extracts in mice
- Estrogens in beef and cancer risk
Meeting venue
The ESMO Symposium on Cancer and Nutrition will take place at the Mövenpick Hotel Zurich Airport
Services for media representatives
Representatives from the press will have access to all the scientific sessions and the
possibility to schedule one-on-one interviews with top speakers and presenters of the studies,
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both in presence and remotely. Please contact the ESMO Press Office at media@esmo.org to
already find out about the preliminary timetable or to book a telephone hook up. The
conference full program is available at http://www.esmo.org/newsroom/events/
About the European Society for Medical Oncology (ESMO)
The European Society for Medical Oncology (ESMO) is a non-profit organization which
promotes medical oncology and a multidisciplinary approach to cancer treatment. ESMO is a
community of oncology professionals that unites key stakeholders who share the common
objective of preventing cancer, fostering a favourable environment for scientific research, and
advocating for equal access to high quality cancer treatment. As the leading European
professional medical oncology society, ESMO offers state-of-the-art educational and training
programs which provide the oncology community with a platform to disseminate the most
up-to-date scientific research and information available. ESMO's scientific journal, Annals of
Oncology, ranks among the top clinical oncology journals worldwide. ESMO is an authoritative
voice in the fight against cancer and offers consultative expertise to oncology organizations
and European authorities on important issues related to cancer research, prevention,
diagnosis, treatment and cure.
3 月 13 日
Success Of Pfizer Pancreatic Cancer Drug Stops Trial
Global drug company Pfizer Inc announced yesterday, 12 March, that a phase 3 clinical trial of
its pancreatic cancer drug Sutent (sunitinib malate) stopped early because the drug showed
significant benefits in patients.
Sutent is designed to treat patients with advanced pancreatic islet cell tumors, also known as
pancreatic neuroendocrine tumors.
It is an oral multi-kinase inhibitor (blocks the action of molecules that help the cancer to spread)
and is already approved for the treatment of both advanced renal cell carcinoma (RCC) and
second-line gastrointestinal stromal tumor (GIST). More than 38,000 patients with these
diseases have been treated with the drug, both in clinical settings and in trials.
The independent Data Monitoring Committee (DMC) that was overseeing this trial
recommended it stop after finding that the drug had shown greater progression-free survival
compared to placebo (patients lived longer without the cancer spreading), and best supportive
care in patients with pancreatic islet cell tumors, said Pfizer in a press statement. Once the trial
data is fully analyzed, it will be presented at a scientific meeting, they added.
Pancreatic islet cell tumors are rare, with an incidence of 5 to 10 per million worldwide annually.
Such tumors include insulinomas, glucagonomas and gastrinomas, and current treatment
options are limited.
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The participating centers have now been informed of the decision, so all the patients taking
part in the trial can choose to continue on Sutent or switch from placebo to the drug.
Dr Mace Rothenberg, senior vice president of medical development and clinical affairs for
Pfizer's Oncology Business Unit told the press:
"We are delighted by these findings which demonstrate that Sutent provides a benefit for
patients with advanced, well-differentiated pancreatic islet cell tumors -- a rare cancer with
limited treatment options."
"These and previously reported phase 2 data contribute to the growing body of evidence
indicating activity with sunitinib in patients with pancreatic islet cell tumors," he added.
The phase 3 trial followed the successful completion of the phase 2 trial which was reported in
the July 2008 issue of the Journal of Clinical Oncology.
Pfizer reported that this is the second phase 3 trial of Sutent that has stopped early on the
recommendation of the trial's DMC because it has shown benefits to patients. In January 2005,
when Sutent was being trialled for use with GIST patients, the trial was unblinded early when
results showed the drug delayed tumor progression compared to placebo.
The company is also looking to test the drug in phase 3 trials for the treatment of other solid
tumors, including advanced breast cancer, advanced non-small cell lung cancer, advanced
colorectal cancer, advanced hepatocellular carcinoma and advanced hormone-refractory
prostate cancer.
According to the Associated Press, the news sent Pfizer shares up by nearly 10 per cent on
Thursday. Sutent is already the New-York based company's best-selling cancer drug, earning
847 million dollars in sales in 2008, of which 254 million was in the US, said the AP
announcement.
3 月 13 日
Cephalon Response To NICE Guidance On Advanced Breast
Cancer Treatment Published 25 February 2009, UK
Liz Hardaker, medical director of Cephalon UK. "We are disappointed and surprised that NICE
has not taken this opportunity to distinguish between different forms of anthracycline treatment;
specifically the use of liposomal-encapsulated doxorubicin.
"Myocet, in combination with cyclophosphamide, is indicated for the first line treatment of
metastatic breast cancer in women (SmPC). A number of published clinical trials have shown
liposomal-encapsulated doxorubicin to provide improved safety by reducing cardiac toxicity
whilst retaining comparable efficacy compared with conventional doxorubicin1,2.
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"For patients previously treated with an anthracycline in early breast cancer, Myocet is more
effective than doxorubicin with a significantly higher overall objective response rate (ORR) and
significantly improved time to treatment failure (TTF).3
"Anthracyclines are a mainstay treatment of metastatic breast cancer but their use is limited by
cumulative dose-related cardiotoxicity and myelosuppression, despite long anthracycline-free
intervals in many patients. Liposomal-encapsulated doxorubicin was developed to address
these toxicity issues1.
"NICE guidelines play an important part in determining appropriate treatment for patients and
the failure of NICE to recognise the place of liposomal-encapsulated doxorubicin in its latest
guidance may limit access to a treatment that could provide benefit to eligible patients."
Justin Stebbing, consultant medical oncologist and senior lecturer at Charing Cross Hospital
said: "We have approved the use of Myocet in selected patients with breast cancer at Imperial
College Healthcare NHS Trust.
"This is based on the data showing efficacy at least as good as other 'conventional'
anthracyclines, and a lack of cardiac toxicity which is now particularly relevant, as patients with
all forms of breast cancer are living longer."
References:
1 Batist G et al. J Clin Oncol 2001;19(5): 1444-1454.
2 Harris L, Batist G, Belt R et al. Cancer 2002; 94: 26-36
3 Batist G et al. Anti-Cancer Drugs 2006; 17: 587-595.
3 月 13 日
Cancer Advocates, Survivors Address The 'Now What?' Stage Of
Cancer
Survivorship is the new buzz word in cancer care as advances in the treatment and detection
of cancer have resulted in an estimated 12 million cancer survivors in the United States alone.
However, cancer survivors need assistance navigating the complex issues they face after
treatment. ABC News veteran Sam Donaldson echoed this fact and raised a host of
survivorship issues while moderating a roundtable held at the National Comprehensive Cancer
Network's 14th Annual Conference on March 12.
"A cancer survivor," Ellen Stovall of the National Coalition for Cancer Survivorship explained,
"is a term used to describe anyone who has been diagnosed with cancer as well as caregivers
and loved ones of those diagnosed with the disease." The term survivorship was first coined in
1985, but was expanded to include family members and caregivers since "no one can survive
cancer alone."
Panelist and cancer advocate Elizabeth Edwards noted the importance of a strong support
system because as a cancer survivor, "the most benign things will scare you to death." She
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relayed a story about how she recently thought a rough spot on her neck may have been a
skin cancer metastasis, when it was only a curling iron burn.
Mary McCabe, RN, BS, MA, from Memorial Sloan-Kettering Cancer Center touched on the
"fear factor" that cancer survivors continue to live with explaining that her patients often
energize themselves to get through the initial treatment, but then they can "run out of gas for
the 'what's next' period that comes after treatment."
The panelists noted that with a documented shortage of oncologists, survivors are challenging
the capacity of our healthcare system when they become reluctant to leave their oncologist at
the conclusion of treatment. Furthermore, the lack of clear evidence for what constitutes best
practices in caring for patients with a history of cancer contributes to a wide variation in care.
Incorporating cancer into a person's whole life, "is something that has not traditionally been
appreciated by clinicians in their clinical practice," said Ellen Stovall, National Coalition for
Cancer Survivorship.
Acknowledging this concern, Douglas Blayney, MD, of the University of Michigan
Comprehensive Cancer Center, noted the importance of transition care plans for survivors. "As
oncologists, we're usually focused on recurrence, surveillance, and a secondary cancer
developing. However, the transition visit is imperative and needs to be a defined episode to
recognize the psychosocial issues attributed to cancer survivorship."
Author and New York Times columnist Jane Brody applauded Dr. Blayney's approach stating
that, "Clinicians need to initiate the conversation of psychosocial issues that may arise after
treatment at the time of diagnosis" and that "patients should not be responsible for reinventing
the wheel" in terms of receiving referrals to survivorship resources.
Catherine Alfano, PhD, National Cancer Institute Office of Cancer Survivorship, stressed
incorporating the results of a recent Institute of Medicine report on cancer care that identified
the need for a screening system that would address the myriad of physical and emotional
issues cancer survivors face after treatment. She noted that this would benefit the clinician as
well as the patient as they could easily determine what the patient's top concerns were and
refer them to appropriate care.
Kenneth Miller, MD, of the Dana Farber Cancer Institute, also encouraged the development of
a standard "check list of-sorts" that clinicians could utilize to ensure survivorship would
become a part of their treatment plan for each patient.
The need for consistent and clear communication between healthcare providers and cancer
survivors was a topic everyone on the panel felt was lacking and needed improvement.
Ellen Stovall felt that patients often aren't given enough credit for what they can understand.
Elizabeth Edwards mentioned that she felt that her clinicians "were honest, but vague where
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they thought they needed to be" because perhaps the assumption was that she couldn't
emotionally handle the prognosis. Jane Brody also noted that she's surprised at how many
clinical questions her readers ask her instead of their clinicians.
Dr. Blayney acknowledged the communication gap and stressed again the importance of open
communication on past, present, and future issues that arise with cancer survivors.
In conclusion, Mr. Donaldson praised the current administration for earmarking funds for
cancer research. Dr. Alfano affirmed the NCI's commitment to work with the new administration
and obtain additional funding dedicated to the entire spectrum of cancer care including
survivorship.
About the National Comprehensive Cancer Network
The National Comprehensive Cancer Network (NCCN), a not-for-profit alliance of 21 of the
world's leading cancer centers, is dedicated to improving the quality and effectiveness of care
provided to patients with cancer. Through the leadership and expertise of clinical professionals
at NCCN Member Institutions, NCCN develops resources that present valuable information to
the numerous stakeholders in the health care delivery system. As the arbiter of high-quality
cancer care, NCCN promotes the importance of continuous quality improvement and
recognizes the significance of creating clinical practice guidelines appropriate for use by
patients, clinicians, and other health care decision-makers. The primary goal of all NCCN
initiatives is to improve the quality, effectiveness, and efficiency of oncology practice so
patients can live better lives.
The NCCN Member Institutions are: City of Hope Comprehensive Cancer Center, Los Angeles,
CA; Dana-Farber/Brigham and Women's Cancer Center | Massachusetts General Hospital
Cancer Center, Boston, MA; Duke Comprehensive Cancer Center, Durham, NC; Fox Chase
Cancer Center, Philadelphia, PA; Huntsman Cancer Institute at the University of Utah, Salt
Lake City, UT; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance,
Seattle, WA; Arthur G. James Cancer Hospital & Richard J. Solove Research Institute at The
Ohio State University, Columbus, OH; The Sidney Kimmel Comprehensive Cancer Center at
Johns Hopkins, Baltimore, MD; Robert H. Lurie Comprehensive Cancer Center of
Northwestern University, Chicago, IL; Memorial Sloan-Kettering Cancer Center, New York, NY;
H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; Roswell Park Cancer Institute,
Buffalo, NY; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University
School of Medicine, St. Louis, MO; St. Jude Children's Research Hospital/University of
Tennessee Cancer Institute, Memphis, TN; Stanford Comprehensive Cancer Center, Stanford,
CA; University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL;
UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of
Michigan Comprehensive Cancer Center, Ann Arbor, MI; UNMC Eppley Cancer Center at The
Nebraska Medical Center, Omaha, NE; The University of Texas M. D. Anderson Cancer Center,
Houston, TX; and Vanderbilt-Ingram Cancer Center, Nashville, TN.
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For more information on NCCN, please visit http://www.nccn.org.
National Comprehensive Cancer Network
3 月 14 日
Breakthrough Discovery Reveals How Circadian Rhythm-Cell
Energy Link Can Lead To New Treatments
UC Irvine researchers have discovered that circadian rhythms - our own body clock - regulate
energy levels in cells. The findings have far-reaching implications, from providing greater
insights into the bond between the body's day-night patterns and metabolism to creating new
ways to treat cancer, diabetes, obesity and a host of related diseases.
In addition, Paolo Sassone-Corsi, Distinguished Professor and Chair of Pharmacology, and his
colleagues found that the proteins involved with circadian rhythms and metabolism are
intrinsically linked and dependent upon each other. Their study appears online in Science
Express.
"Our circadian rhythms and metabolism are closely partnered to ensure that cells function
properly and remain healthy," Sassone-Corsi said. "This discovery opens a new window for us
to understand how these two fundamental processes work together, and it can have a great
impact on new treatments for diseases caused by cell energy deficiencies."
Circadian rhythms of 24 hours govern fundamental physiological functions in almost all
organisms. The circadian clocks are the essential time-tracking systems in our bodies that
anticipate environmental changes and adapt to the appropriate time of day. Disruption of these
rhythms can profoundly influence human health and has been linked to obesity, diabetes,
insomnia, depression, coronary heart diseases and cancer.
Sassone-Corsi already had identified that the enzyme protein CLOCK is an essential
molecular gear of the circadian machinery and interacts with a protein, SIRT1, which senses
cell energy levels and modulates aging and metabolism.
In this study, he and his colleagues show that CLOCK works in balance with SIRT1 to direct
activity in a cell pathway by which metabolic proteins send signals called the NAD+ salvage
pathway. In turn, a key protein in that pathway, NAMPT, helps control CLOCK levels, creating a
tightly regulated codependency between our circadian clock and metabolism.
"When the balance between these two vital processes is upset, normal cellular function can be
disrupted," Sassone-Corsi said. "And this can lead to illness and disease."
The findings suggest that proper sleep and diet may help maintain or rebuild this balance, he
said, and also help explain why lack of rest or disruption of normal sleep patterns can increase
hunger, leading to obesity-related illnesses and accelerated aging.
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The specific interaction between CLOCK and SIRT1 and the NAD+ salvage pathway also
presents a starting point for drug development aimed at curbing cell dysfunction and death,
thereby helping to solve major medical problems such cancer and diabetes.
Notes:
Yasukazu Nakahata, Milota Kaluzova, Saurabh Sahar and Giuseppe Astarita of UCI
participated in the study, which was supported by the Cancer Research Coordinating
Committee of the University of California and the National Institutes of Health.
About the University of California, Irvine: The University of California, Irvine is a top-ranked
university dedicated to research, scholarship and community service. Founded in 1965, UCI is
among the fastest-growing University of California campuses, with more than 27,000
undergraduate and graduate students. The top employer in dynamic Orange County, UCI
contributes an annual economic impact of $4.2 billion. For more UCI news, visit
http://www.today.uci.edu.
Source: Tom Vasich
3 月 16 日
Sutent Significantly Increases Progression Free Survival For
Patients With Advanced Pancreatic Islet Cell Tumors, Study
Stopped Early
Pfizer Inc announced that a phase 3 clinical trial of Sutent (sunitinib malate) has been stopped
early after the drug showed significant benefit in patients with advanced pancreatic islet cell
tumors, also known as pancreatic neuroendocrine tumors.
An independent Data Monitoring Committee (DMC) recommended halting the trial after
concluding that Sutent demonstrated greater progression-free survival compared to placebo
plus best supportive care in patients with pancreatic islet cell tumors.
"We are delighted by these findings which demonstrate that Sutent provides a benefit for
patients with advanced, well-differentiated pancreatic islet cell tumors - a rare cancer with
limited treatment options," said Dr. Mace Rothenberg, senior vice president of medical
development and clinical affairs for Pfizer's Oncology Business Unit. "These and previously
reported phase 2 data contribute to the growing body of evidence indicating activity with
sunitinib in patients with pancreatic islet cell tumors."
Pfizer has notified clinical trial investigators involved in the trial and regulatory agencies of the
DMC recommendations. All patients in the trial will have the option to continue taking Sutent or
be switched from placebo to Sutent. The full data set from this trial is being analyzed and more
details will be presented at an upcoming scientific meeting.
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This phase III trial of sunitinib in patients with advanced pancreatic islet cell tumors was
initiated based on the results of a earlier phase II trial published in the Journal of Clinical
Oncology(July 2008).
In contrast to exocrine pancreatic adenocarcinoma, pancreatic islet cell tumors are rare,
indolent tumors of the endocrine pancreas with an incidence of 5-10 per million worldwide
annually. Pancreatic islet cell tumors include insulinomas, glucagonomas and gastrinomas.
Current treatment options are limited.
Sutent is currently approved for both advanced renal cell carcinoma (RCC) and second-line
gastrointestinal stromal tumor (GIST), based on efficacy and safety data from large,
randomized Phase 3 clinical trials. Sutent has played an important role in reshaping the
treatment landscape for these two difficult-to-treat cancers. To date, more than 38,000 patients
globally have been treated with Sutent in the clinical setting and trials.
This is the second phase III Sutent trial Pfizer has stopped early on the recommendation of an
independent data monitoring committee due to benefit. In January 2005, a phase III trial in
GIST was unblinded early when a planned interim analysis showed significantly longer time to
tumor progression with Sutent compared to placebo.
Sunitinib Clinical Research Program
Pfizer is pursuing a broad development program for sunitinib malate and is studying its role in
the potential treatment of various solid tumors including advanced breast cancer, advanced
non-small cell lung cancer, advanced colorectal cancer, advanced hepatocellular carcinoma
and advanced hormone-refractory prostate cancer in Phase 3 trials.
Healthcare professionals who are interested in learning more about sunitinib trials that are
open for enrollment can visit the SUN program web site at http://www.suntrials.com. Patients
with questions should contact their treating physician or obtain additional information through
Pfizer, by calling 1-800-TRY-FIRST (1-800-879-4377).
About SUTENT® (sunitinib malate)
SUTENT is an oral multi-kinase inhibitor approved for the treatment of advanced RCC and
GIST after disease progression on or intolerance to imatinib mesylate.
SUTENT works by blocking multiple molecular targets implicated in the growth, proliferation
and spread of cancer. Two important SUTENT targets, vascular endothelial growth factor
receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR), are expressed by
many types of solid tumors and are thought to play a crucial role in angiogenesis, the process
by which tumors acquire blood vessels, oxygen and nutrients needed for growth. SUTENT
also inhibits other targets important to tumor growth, including KIT, FLT3 and RET.
88
Important SUTENT® (sunitinib malate) Safety Information
Women of child bearing age who are (or become) pregnant during therapy should be informed
of the potential for fetal harm while on SUTENT.
Decreases in left ventricular ejection fraction (LVEF) to below the lower limit of normal (LLN)
have been observed. Patients with concomitant cardiac conditions should be carefully
monitored for clinical signs and symptoms of congestive heart failure.
Patients should be monitored for hypertension and treated as needed with standard
antihypertensive therapy. Complete blood counts (CBCs) with platelet count and serum
chemistries should be performed at the beginning of each treatment cycle for patients
receiving treatment with SUTENT.
The most common adverse reactions in advanced RCC and GIST clinical trials were fatigue,
asthenia, diarrhea, nausea, mucositis/stomatitis, vomiting, dyspepsia, abdominal pain,
constipation, hypertension, rash, hand-foot syndrome, skin discoloration, altered taste,
anorexia and bleeding.
For more information on SUTENT and Pfizer Oncology, including full prescribing information
for SUTENT (sunitinib malate), please visit http://www.pfizer.com.
DISCLOSURE NOTICE: The information contained in this release is as of March 12, 2009.
Pfizer assumes no obligation to update any forward-looking statements contained in this
release as the result of new information or future events or developments.
This release contains forward-looking information about certain potential additional indications
for Sutent, including their potential benefits, that involves substantial risks and uncertainties.
Such risks and uncertainties include, among other things, the uncertainties inherent in
research and development; decisions by regulatory authorities regarding whether and when to
approve any supplemental drug applications that may be filed for additional indications for
Sutent as well as their decisions regarding labeling and other matters that could affect the
availability or commercial potential of any such additional indications; and competitive
developments.
A further list and description of risks and uncertainties can be found in Pfizer's Annual Report
on Form 10-K for the fiscal year ended December 31, 2008 and in its reports on Form 10-Q
and Form 8-K.
3 月 16 日
Antigenics' Oncophage Cancer Vaccine Receives European
Orphan Drug Designation For Brain Cancer
89
Antigenics Inc. (NASDAQ: AGEN) announced that Oncophage® (vitespen) has been granted
a positive recommendation for orphan drug designation for the treatment of glioma by the
Committee for Orphan Medical Products (COMP) of the European Medicines Agency (EMEA).
This designation provides Antigenics with, among other benefits, 10 years of potential market
exclusivity if the product is approved for marketing in the European Union (EU).
This is the second indication for which the EMEA has granted orphan drug status to
Oncophage. In April 2005, Oncophage received orphan drug designation in the European
Union for the treatment of renal cell carcinoma (kidney cancer). Subsequently, Antigenics
submitted a Marketing Authorization Application (MAA) to the EMEA in October 2008
requesting approval for Oncophage in earlier-stage, localized renal cell carcinoma.
"We are committed to supporting the evaluation of Oncophage in patients diagnosed with
glioma, as this remains a life-threatening disease with limited treatment options," stated Garo
Armen, PhD, chairman and CEO of Antigenics. "Furthermore, orphan drug status has the
potential to accelerate the development of Oncophage in this patient population, which is
critical given the poor survival rates."
The EMEA regulation on orphan medicinal products is designed to promote the development
of drugs, which may provide significant benefit to patients suffering from rare diseases
identified as "life-threatening or very serious." In addition to potential 10-year EU market
exclusivity following marketing approval, orphan drug status provides regulatory assistance,
reduced regulatory fees associated with applying for marketing approval, and protocol
assistance.
About Oncophage
In April 2008, Oncophage was approved in Russia for the adjuvant treatment of kidney cancer
patients at intermediate-risk for disease recurrence. In October 2008, Antigenics submitted a
MAA to the EMEA requesting approval for Oncophage in earlier-stage, localized renal cell
carcinoma.
Derived from each individual's tumor, Oncophage contains the 'antigenic fingerprint' of the
patient's particular cancer and is designed to reprogram the body's immune system to target
only cancer cells bearing this fingerprint. Oncophage is intended to leave healthy tissue
unaffected and limit the debilitating side effects typically associated with traditional cancer
treatments such as chemotherapy and radiation therapy. Oncophage has been studied in
Phase 3 clinical trials for the treatment of kidney cancer and metastatic melanoma and is
currently being investigated in a Phase 1/2 trial in recurrent glioma.
Oncophage has also received fast track and orphan drug designations from the U.S. Food and
Drug Administration for both kidney cancer and metastatic melanoma.
About Brain Tumors
90
Glioma is the most common type of brain tumor and is currently a fatal disease impairing areas
such as thinking, personality and movement. The National Cancer Institute estimates that
about 19,000 cases are diagnosed every year in the U.S. and according to historical estimates,
the median survival of patients with previously treated glioma is typically three to six months.
About Antigenics
Antigenics (NASDAQ: AGEN) is a biotechnology company working to develop treatments for
cancers and infectious diseases. For more information, please visit http://www.antigenics.com.
This press release contains forward-looking statements, including statements regarding the
potential impact of EMEA orphan drug designation, and the development, clinical, and
commercial potential of Oncophage. These statements are subject to risks and uncertainties
that could cause actual results to differ materially from those projected in these forward-looking
statements. These risks and uncertainties include, among others, that Oncophage may not be
approved for sale outside of Russia and, regardless of approval, may not succeed
commercially; that orphan drug status may not be maintained in the event of legislative
changes or introduction of a more efficacious product in this disease category; and the factors
described in the company's periodic filings with the Securities and Exchange Commission.
Please see the factors described under the Risk Factors section of our Quarterly Report on
Form 10-Q filed with the Securities and Exchange Commission for the period ended
September 30, 2008 for a more complete discussion of these and other risk factors. The grant
of orphan designation by the EMEA does not assure rapid regulatory decision-making or
approval. Antigenics cautions investors not to place considerable reliance on the
forward-looking statements contained in this press release. These statements speak only as of
the date of this document, and Antigenics undertakes no obligation to update or revise the
statements. All forward-looking statements are expressly qualified in their entirety by this
cautionary statement. Antigenics' business is subject to substantial risks and uncertainties,
including those identified above. When evaluating Antigenics' business and securities,
investors should give careful consideration to these risks and uncertainties.
3 月 16 日
Scientists Find Regulatory Molecule That May Contribute To The
Formation Or Suppression Of Tumours
Scientists in Singapore and the US have recently found that a microRNA, named
microRNA-125b, is a novel regulator of p53, an important protein that safeguards cells against
cancers. The research finding was reported on March 17, 2009 in the prestigious journal,
Genes & Development.
The unique characteristics of every cell type are determined by a group of proteins produced in
the cell by molecules known as messenger RNAs (mRNAs). The quantity of protein produced
by each mRNA must therefore be tightly regulated, and several mechanisms had evolved in
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nature to do this. An ancient mechanism, common to plants and animals, involve a family of
small regulatory molecules known as microRNAs.
MicroRNAs play complex roles in the simultaneous fine-tuning of many genes in each cell - a
role not yet well-understood by biologists. It is a complicated, delicate balance that can be
profoundly disturbed if just a few microRNAs go awry. Recent research reveals that
microRNAs are abundant in the cell and that they play important roles in development and in
many diseases.
During embryonic development, this microRNA keeps the level of p53 low to avoid excessive
cell death. On the other hand, if a DNA is damaged, the microRNA level is reduced to allow an
increase in p53, which eliminates damaged cells and thus prevents tumour formation.
The discovery will be published in Genes & Development on March 17, 2009.
Source
Winnie Serah Lim
Office of Corporate Communications, & Office of Administrative Management
Genome Institute of Singapore
60 Biopolis Street #02-01 Genome
Singapore 138672
3 月 16 日
Wide-Reaching Global Survey Reveals Majority Of Women Living
With Metastatic Breast Cancer Desire Increased Public Attention
A new global survey of 950 women living with metastatic breast cancer (MBC) in nine countries
(the United Kingdom, France, Spain, Belgium, Poland, the United States, Argentina, Egypt and
Mexico) found that despite the negative impact of their disease, a majority still enjoy life and
desire public attention that recognizes their unique experiences. Based on the survey results,
the international committee of experts overseeing the survey advocate tailored education
programs to raise awareness of the needs of women with MBC. Results from this survey,
which was conducted by Harris Interactive® and sponsored by Pfizer Oncology, were
presented today at the 11th International Conference on Primary Therapy of Early Breast
Cancer in St. Gallen, Switzerland.
Among the reported findings from the BRIDGE Survey (Bridging Gaps, Expanding Outreach Metastatic Breast Cancer Patient Survey), one in two women (53 percent) believe MBC
receives too little public attention, and more than two in five women (44 percent) report being
afraid to talk openly about their experiences. Nearly seven in 10 women (67 percent) desire
increased public awareness of MBC, such as increased media attention of people living with
MBC (53 percent) and recognition of public figures with MBC (49 percent).
"In many countries, the public face of breast cancer has largely been focused on early stage
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disease, which has led to a deficiency of resources and attention for those who develop
metastatic breast cancer," said Professor Lesley Fallowfield, director, Cancer Research UK
Psychosocial Oncology Group, University of Sussex, UK, and BRIDGE steering committee
member. "BRIDGE sheds light on the dire need for more public dialogue about metastatic
breast cancer in an effort to make women feel more included among the broader breast cancer
community."
There are an estimated 1.3 million new cases of breast cancer each year. Breast cancer is the
leading cause of cancer death among women worldwide, with an estimated 465,000 annual
deaths. In developed countries, nearly 30 percent of women with early stage breast cancer will
eventually develop metastatic (Stage IV) breast cancer - cancer that has spread beyond the
breast to other parts of the body, including the bones, lungs, liver and brain. In developing
countries, the majority of women with breast cancer are diagnosed with advanced stage or
metastatic disease. Unlike early stage breast cancer, there are no curative therapies for MBC
and patients undergo continuous treatment to control the spread of their disease and
symptoms.
Notably, while the majority (67 percent) of survey respondents recognize that MBC has
negatively impacted most parts of their lives, most (66 percent) also say they are still able to
enjoy life and 50 percent consider themselves to be a cancer "survivor".
"The BRIDGE survey emphasizes the strength of the human spirit. With optimal support and
resources, many women are able to live their lives well with metastatic disease for longer
periods of time," said Musa Mayer, M.S., M.F.A., author, patient advocate and founder of
AdvancedBC.org, and BRIDGE survey steering committee member. "This survey is an
important first step in identifying the needs of this neglected patient population. It provides
impetus for stakeholders worldwide to ensure that these women receive the best support and
care."
The survey also indicated the important role information plays in helping women cope with
MBC, with updates on new research and treatment options the most desired. However, while
75 percent of respondents proactively seek out information on their own to learn about MBC,
over two in five women (45 percent) encounter difficulties locating information and one in two
(51 percent) report that available information does not meet their needs.
"Despite its prevalence, women with metastatic breast cancer often experience feelings of
isolation, as available information and attention from society range from being scant to
sufficient, depending on country and cultural characteristics," said Musa Mayer.
Members of the BRIDGE steering committee recommend that the survey results be used to
improve collaboration among MBC stakeholders and enhance breast cancer initiatives
worldwide, including but not limited to the creation of up-to-date and easily accessible
information on MBC, and the development of education programs that promote public
awareness of the disease. As the survey revealed women's experiences with MBC vary by
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country, efforts to help women must be tailored to be culturally relevant where appropriate.
About the BRIDGE Survey
The BRIDGE Survey is a new, wide-reaching global assessment of the needs, experiences
and attitudes of women living with MBC in multiple countries. This survey was conducted by
Harris Interactive® on behalf of Pfizer Oncology and led by an international steering committee
comprised of seven breast cancer thought leaders and advocates dedicated to addressing the
unmet needs of the MBC community. The survey was conducted between September 16,
2008 and February 18, 2009 among 950 women with MBC age 18 and over in the United
States, Europe, Latin America and Africa. The interviews were conducted using a combination
of telephone, mail or in-person methods. More information on the methodology is available.
For additional information about the BRIDGE Survey, please visit http://www.BridgeMBC.com.
The international steering committee members, who were responsible for the development
and contextualization of the survey, include:
- Elyse S. Caplan, M.A., education director, Living Beyond Breast Cancer, United States;
- Lesley Fallowfield, Bsc., DPhil., FMedSci., director, Cancer Research U.K., Sussex
Psychosocial Oncology Group and Sussex Health Outcomes Research and Education
(SHORE), Brighton and Sussex Medical School, United Kingdom;
- Catherine Glennon, R.N., C.N.A., B.C., M.H.S., O.C.N., North American board member,
International Society of Nurses in Cancer Care; nursing director of cancer services, University
of Kansas Hospital, United States;
- Adrian Huñis, M.D., assistant professor of internal medicine, University of Buenos Aires
School of Medicine; head professor of oncology, Maimonides University, Argentina;
- Musa Mayer, M.S., M.F.A., author and patient advocate, founder, AdvancedBC.org, United
States;
- Ruth Oratz, M.D., F.A.C.P., clinical associate professor of medicine, New York University
School of Medicine, United States; and
- Patricia Spicer, L.M.S.W., breast cancer program coordinator, Cancer Care, United States.
Pfizer Oncology is committed to helping fulfill unmet educational and support needs for MBC
patients worldwide and has embarked on a number of initiatives, including the sponsorship of
an MBC Advocacy Working Group, a cooperative of patient advocates from seven countries,
which recently issued a Consensus Report urging breast cancer stakeholders to improve
collaboration and implement strategies to address unmet needs of women with MBC. This
report was published in the December 2008 issue of the journal, Community Oncology.
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About Metastatic Breast Cancer
Metastatic breast cancer (MBC) is the most advanced stage of breast cancer (Stage IV) and
occurs when cancer has spread beyond the breast to distant parts of the body. Compared to
early stage breast cancer, the prognosis for Stage IV breast cancer is poor, with the majority of
breast cancer-related deaths resulting from complications of metastatic disease. While the life
expectancy for patients with MBC is approximately two to three years, length of survival has
continually increased since the 1990s due to advancements in diagnosis and treatment.
Because metastatic breast cancer remains essentially incurable, current goals of therapy are
focused on relieving symptoms, delaying tumor progression, improving quality of life, and
prolonging survival.
About Harris Interactive®
Harris Interactive is a global leader in custom market research. With a long and rich history in
multimodal research, powered by their science and technology, they assist clients in achieving
business results. Harris Interactive serves clients globally through their North American,
European and Asian offices and a network of independent market research firms.
3 月 16 日
Biothera Receives Approval To Launch Two Phase II Lung Cancer
Trials
German regulatory authorities have granted approval to Biothera to conduct two open label,
multicenter, randomized Phase II clinical trials studying Imprime PGG® administered in
combination with monoclonal antibodies and chemotherapy in patients with non-small cell lung
cancer (NSCLC), the company announced today.
"Our ongoing clinical trial in metastatic colorectal cancer has demonstrated the ability of
Imprime PGG to work synergistically with monoclonal antibody therapy, resulting in significant
improvements in patient outcomes," said Daniel Conners, Biothera founder and chairman. "We
believe that Imprime PGG's unique mechanism of action will result in similar synergies in
NSCLC patients."
Study Designs
In the first trial, Imprime PGG will be administered in combination with Avastin® (bevacizumab)
and two chemotherapeutic agents, carboplatin and paclitaxel. The second trial will study
Imprime PGG in combination with Erbitux® (cetuximab), carboplatin and paclitaxel. Each trial
will enroll up to 90 patients and includes both a treatment arm (consisting of Imprime PGG, a
monoclonal antibody and chemotherapy) and a control arm (consisting of the monoclonal
antibody and chemotherapy alone).
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The primary objective for each study is to determine the anti-tumor effects of Imprime PGG
when used in combination with a monoclonal antibody and chemotherapy, based on overall
response rate as assessed by RECIST (Response Evaluation Criteria in Solid Tumors).
About Non-Small Cell Lung Cancer (NSCLC)
Cancer is a leading cause of death worldwide. Lung cancer claims more lives than any other
cancer, with more than 1.3 million deaths annually. In the U.S., lung is the leading cause of
cancer death for both men and women and claims more lives than colon, breast, and prostate
cancers combined. The National Cancer Institute estimates that there were more than 215,000
new cases of lung cancer last year in the United States. Approximately 75 percent of all
diagnosed lung cancers are due to NSCLC.
About Imprime PGG
Imprime PGG is a targeted immunotherapeutic drug candidate that works synergistically with
anti-tumor monoclonal antibodies through specific innate immune cell activation. Imprime PGG
activates a large population of the body's immune cells (neutrophils) to kill cancer cells. Unlike
other drugs that trigger a broad innate immune response, Imprime PGG selectively activates
immune cells without inducing systemic pro-inflammatory cytokines, which reduces potential
side effects. As a platform therapeutic in oncology, Imprime PGG has the potential to improve
patient response rates for existing monoclonal antibody therapies in approved indications,
create new indications for these drugs and enhance the efficacy of development-stage
monoclonal antibody drugs.
About Biothera, the Immune Health Company
Biothera is a biotechnology company dedicated to improving immune health. The company is
developing pharmaceuticals that engage the innate immune system to fight cancer.
3 月 17 日
Early detection of second breast cancers halves
women's risk of death
A group of international researchers has found the first reliable evidence that early detection
of subsequent breast tumours in women who have already had the disease can halve the
women's chances of death from breast cancer.
According to the research published online today (Wednesday 18 March) in the cancer journal,
Annals of Oncology [1], if the second breast cancer was picked up at its early, asymptomatic
stage, then the women's chances of survival were improved by between 27-47% compared
to women whose second breast cancer was detected at a later stage when symptoms had
started to appear.
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Until now, the impact of early detection of second breast cancers was unclear. Attempts to
investigate it have been complicated by the fact that it is not possible to run randomised
controlled trials because women who have already had one breast cancer are at higher risk of
a relapse or a second breast cancer and, therefore, are generally advised to have regular
breast checks as part of their follow-up care. What studies there have been have not made
adjustments for the main factors that could bias the findings from a non-randomised study
and often have looked at breast cancers occurring in either the same breast (ipsilateral
relapse) or the other breast (contralateral) but not either breast.
The current study looked at 1,044 women who had attended one clinical centre in Florence
(Italy) between 1980-2005 and who had developed a second breast cancer. In that time 455
women had ipsilateral breast cancers (IBC) diagnosed and 589 women had contralateral
breast cancers (CBC) diagnosed. Of these second cancers, 699 (67%) were asymptomatic
and 345 (33%) were symptomatic.
The researchers found that mammography was more sensitive than clinical examination for
detecting second cancers (86% versus 57%). However, 13.8% of cases were only detected
by clinical examination. Asymptomatic cancers were smaller than symptomatic for both IBC
and CBC; early stage cancers were more frequent in asymptomatic (58.1%) than in
symptomatic (22.6%) women; and fewer women with asymptomatic than symptomatic CBC
had node metastases (an indicator that the cancer may have spread).
In the analysis of the results, the researchers (from Italy, Australia and the UK) adjusted to
allow for lead-time bias (bias caused by an earlier detection of the cancer) and length-time
bias (bias caused by the fact that some breast cancers develop more slowly than others and,
therefore, are more likely to be detected at the asymptomatic stage and are less likely to
cause death).
Associate Professor Nehmat Houssami, a breast physician and principle research fellow at the
University of Sydney's School of Public Health, Australia, who led the study, said: "Intuitively,
it makes sense to consider that early detection of second breast cancers will improve
prognosis, since breast cancer survivors have a long-term risk of developing further disease
or relapse in either breast. However, due to a paucity of evidence about this until now,
current recommendations on surveillance of breast cancer survivors vary substantially
between countries and organisations.
"Our study provides new evidence on several aspects of early detection of second breast
cancers. We set out to estimate the effect of early, asymptomatic detection while adjusting
for the two main biases known to be associated with non-randomised studies of the impact of
early detection – lead time and length bias – so we believe that the estimates we report are
more valid than previously reported estimates, while acknowledging the limitation that the
evidence is not from a randomised controlled trial.
"In addition, we have estimated this for early detection of either ipsilateral or contralateral
breast cancer, while other studies have focused on one or the other. So our estimates may be
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more useful for clinicians discussing this aspect of breast cancer follow-up with their
patients."
She continued: "To our knowledge, this is the only study to have taken length-time bias into
account when quantifying the impact of early, asymptomatic detection of breast cancer. This
is important because slow-growing or indolent cancers have a much smaller probability of
proving fatal, and this group of women will tend to be over-represented in the early-detected
cancers, biasing the effect of screening to make it appear more beneficial."
In their paper, the researchers write: "Recommendations on follow-up after treatment of
early breast cancer should consider our findings, which suggest that early detection of second
breast cancer events improves prognosis in this ever-increasing group of women."
Prof Houssami said: "Periodic surveillance of women with BC is currently under scrutiny in
some countries and questions have been raised as to the value of sustained follow-up of
breast cancer survivors in some health settings. So I think this work provides a timely
reminder of the potential benefit of early detection of second breast cancers and supports
ongoing surveillance in this group of women."
She said that their finding that nearly 14% of second breast cancers were only detected by
clinical examination and that mammograms had a sensitivity of 86% was also important.
"There are health settings where new imaging (ultrasound or MRI) is advocated for screening
because of the belief that mammography is not sufficient and misses too many cancers in
breast cancer survivors. Our data suggest that mammography, with clinical examination, is
sensitive and effective (with the caveat that the Florence centre where the study originated
has established experience in mammography of at least 40 years). We feel that additional
screening imaging should only be used selectively, for example, in women with extremely
dense breasts, or when investigating questionable findings from the mammogram or clinical
examination."
Prof Houssami concluded: "The next step is to determine how to maximise early detection in
this specific setting while ensuring feasibility and efficiency. One possibility currently under
exploration would be to estimate the risk of a symptomatic tumour and the stage of the
symptomatic tumour by time since the last mammogram. There are many questions about
the optimal process and model of surveillance, such as frequency for surveillance and who
should be performing longer-term surveillance in breast cancer patients, that we have not
addressed in this study. These issues require further research."
3 月 17 日
Link between religious coping and aggressive
treatment in terminally ill cancer patients
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BOSTON ––– In a new study of terminally ill cancer patients, researchers at Dana-Farber
Cancer Institute found that those who draw on religion to cope with their illness are more
likely to receive intensive, life-prolonging medical care as death approaches –– treatment
that often entails a lower quality of life in patients' final days.
Previous research has shown that more religious patients often prefer aggressive end-of-life
(EOL) treatment. The new study –– to be published in the March 18 issue of the Journal of the
American Medical Association –– examined whether these patients actually receive such care.
The study's findings suggest that physicians tend to comply with religious patients' wishes for
more aggressive care.
"Recent research has shown that religion and spirituality are major sources of comfort and
support for patients confronting advanced disease," says the study's senior author, Holly
Prigerson, PhD, of Dana-Farber and Brigham and Women's Hospital (BWH). "We focused
specifically on positive religious coping, on people who rely on their faith to handle the
stresses of serious illness and approaching death. Our findings indicate that patients who turn
to religion to cope in times of crisis, such as when facing death, are more likely to receive
aggressive care when they die."
The study involved 345 advanced cancer patients at seven hospital and cancer centers
around the country. Participants were interviewed about their means of coping with the
illness, their use of advance care planning tools such as living wills and durable power of
attorney, and their preferences regarding end-of-life treatment. Investigators then tracked
each patient's course of care during the remainder of his or her life.
An analysis of the data showed that patients identified as positive religious copers had nearly
three times the odds of receiving life-prolonging care, in the form of being on a ventilator or
receiving cardiopulmonary resuscitation, in the final week of life. Even after researchers
accounted for the influence of important factors such as age, ethnicity, or other coping
techniques, the connection between religious coping and aggressive EOL care held up.
The researchers also found that religious copers in the study were less likely to have
completed advance medical directives, such as a living will or do-not-resuscitate order, which
can limit the extent of such interventions in advance. The effects of religious coping on the
use of intensive medical care in the last week of life remained significant even after adjusting
for differences in advance care planning.
In interpreting the results, study lead author Andrea Phelps, MD, of Dana-Farber and Beth
Israel Deaconess Medical Center (BIDMC), and a clinical fellow in medicine at Harvard Medical
School, says that "beyond the significance of religious faith in coping with the emotional
challenge of incurable cancer, it is important to recognize how religious coping factors into
extremely difficult decisions confronting patients as their cancer progresses and death
appears imminent. Beyond turning to doctors for advice, patients often look to God for
guidance in these times of crisis."
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The study did not explore why religious copers often tend to prefer and receive extensive
end-of-life care, the authors note. The researchers hope to examine such questions in future
studies.
"Our results highlight how patients' ways of coping, particularly their use of religious coping,
factor prominently into the ultimate medical care patients receive. This suggests that
clinicians should be attentive to terminally ill patients' religious views as they discuss
prognosis and treatment options with them," said Prigerson, who is also an associate
professor of psychiatry at Harvard Medical School. "A greater understanding of the basis of
patients' medical choices can go a long way toward achieving shared goals of care.
###
Financial support for the study was provided by grants from the National Cancer Institute, the
National Institute of Mental Health, and the Fetzer Institute.
The study's co-authors include Deborah Schrag, MD, MPH, Tracy Balboni, MD, Alexi Wright,
MD, Elizabeth Trice, MD, and Matthew Nilsson, of Dana-Farber; Paul Maciejewski, PhD, John
Peteet, MD, and Susan Block, of Dana-Farber and BWH; and M. Elizabeth Paulk, MD, of the
University of Texas Southwestern Medical Center, Dallas.
Dana-Farber Cancer Institute (www.danafarber.org) is a principal teaching affiliate of the
Harvard Medical School and is among the leading cancer research and care centers in the
United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC),
designated a comprehensive cancer center by the National Cancer Institute.
3 月 17 日
New tumor markers determine therapy intensity
Genetic aberrations in childhood brain tumors provide precise information on the
course of the disease; Heidelberg researchers publish in the Journal of Clinical
Oncology
Characteristic changes in the DNA of medulloblastoma, the most frequent
malignant brain tumor in childhood, indicate precisely how aggressively
the tumor will continue to spread and what the chances of disease relapse
are. Researchers at the Center for Pediatric and Adolescent Medicine at
the Heidelberg University Hospital and the German Cancer Research Center
have discovered this correlation. With this new set of tumor markers, the
intensity of treatment can be adjusted individually and the potentially
damaging effects reduced. The results have now been published online in
the prestigious Journal of Clinical Oncology.
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Medulloblastoma is the most frequent childhood brain tumor
The most common malignant brain tumor in childhood is the medulloblastoma
– every year, more than 100 children in Germany develop this tumor of
the cerebellum and some 30-40 children die from it. The first symptoms
generally appear at primary school age, but the tumor, which can already
arise during embryonal development, can also occur in babies and toddlers.
Aggressive radiation and chemotherapy regimens after surgery can
permanently damage the brain of the growing child, for example, leading
to coordination disorders and limited growth.
"Using the characteristic changes in the genetic makeup of
medulloblastoma, we can predict more accurately than with conventional
methods how a patient will respond to therapy and how great the risk is
that the tumor will return after surgery and subsequent radiation and
chemotherapy," explained Dr. Stefan Pfister, who works with his team in
the department of pediatric oncology at the Center for Pediatric and
Adolescent Medicine (Medical Director: Professor Dr. Dr. Andreas Kulozik)
and in the department of molecular genetics at the German Cancer Research
Center (Director: Professor Dr. Peter Lichter). Thus far, oncologists
could estimate this risk only on the basis of histology findings, age at
diagnosis, residual tumor after surgery, and existence of metastases at
diagnosis.
Patients with a poor prognosis can be treated more intensively
Stefan Pfister and his research group "Molecular Genetics of Pediatric
Brain Tumors" first described the new tumor markers in the medulloblastoma
in 2007. For the current study, he examined tumor samples from 340 patients
and compared the documented course of disease with genetic aberrations
in the tumor DNA. Aberrations were seen at the chromosome level, the units
in which the entire genetic information is distributed and contained. Each
chromosome contains large amounts of genetic information; the entire
genetic material of humans is distributed in 23 such portions, each of
which is usually present in two copies (2 x 23 chromosomes). Stefan Pfister
discovered that if entire segments of chromosomes number 6 and 17 are
present in three copies (instead of the usual 2 copies) in the genetic
material of the brain tumors, the patient's prognosis is poor. If however,
one copy of chromosome 6 is missing in the tumor, the patients in the
collective observed always survived. The combination of these and other
characteristics led to a classification of the patients in a total of five
groups requiring varying levels of intensity in treatment.
"With these markers, we can reliably identify patients with a poor
prognosis and treat them more intensely from the start," said Dr. Stefan
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Pfister. "At the same time, we can reduce the treatment intensity for
patients who will presumably respond especially well to radiation and
chemotherapy. We can thus reduce consequential damage and the risk of
secondary malignancies."
Another advantage of the new markers – the test is very robust and can
be carried out within 48 hours in any neuropathology laboratory on tissue
samples conventionally preserved in paraffin.
BMBF promotes the search for other tumor markers
The prospective validation of these markers in an independent patient
cohort and the search for the simplest and most reliable methods of
analysis is now the goal of a project promoted by the Federal Ministry
for Education and Research (BMBF) entitled "Molecular Diagnostics," in
which the university hospitals of Bonn, Mainz, Düsseldorf, Würzburg, and
Heidelberg as well as the German Cancer Research Center in Heidelberg are
participating under the coordination of Dr. Stefan Pfister.
###
Contact person:
Dr. Stefan Pfister
Head of the research group "Molecular Genetics of Pediatric Brain Tumors"
Center for Pediatric & Adolescent Medicine
Heidelberg University Hospital
Clinic for Oncology, Hematology, Immunology, and Pneumonology
phone: +49 6221 / 56 45 55
e-mail: s.pfister@dkfz.de
References:
Outcome prediction in pediatric medulloblastoma based on DNA copy-number
aberrations of chromosomes 6q, 17q, and the MYC/MYCN loci. Stefan Pfister,
Marc Remke, Axel Benner, Frank Mendrzyk, Grischa Toedt, Jörg Felsberg,
Andrea Wittmann, Frauke Devens, Nicolas U. Gerber, Stefan Joos, Andreas
Kulozik, Guido Reifenberger, Stefan Rutkowski, Otmar D. Wiestler,
Bernhard Radlwimmer, Wolfram Scheurlen, Peter Lichter and Andrey
Korshunov. J. Clin. Oncol. 2009, March 2nd online ahead of print.
More information on the internet:
http://www.klinikum.uni-heidelberg.de/Klinik-fuer-Kinder-und-Jugendme
dizin.760.0.html
Heidelberg University Hospital and Medical Faculty:
Internationally recognized patient care, research, and teaching
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Heidelberg University Hospital is one of the largest and most prestigious
medical centers in Germany. The Medical Faculty of Heidelberg University
belongs to the internationally most renowned biomedical research
institutions in Europe. Both institutions have the common goal of
developing new therapies and implementing them rapidly for patients. With
about 7,000 employees, training and qualification is an important issue.
Every year, around 500,000 patients are treated on an inpatient or
outpatient basis in more than 40 clinics and departments with 1,600 beds.
Currently, about 3,100 future physicians are studying in Heidelberg; the
reform Heidelberg Curriculum Medicinale (HeiCuMed) is one of the top
medical training programs in Germany.
3 月 17 日
Tracking Down And Attacking Cancer Cells Using Nanoscopic
Probes
A researcher has developed probes that can help pinpoint the location of tumors and might
one day be able to directly attack cancer cells.
Joseph Irudayaraj, a Purdue University associate professor of agricultural and biological
engineering, developed the nanoscale, multifunctional probes, which have antibodies on board,
to search out and attach to cancer cells.
A paper detailing the technology was released last week in the online version of Angewandte
Chemie, an international chemistry journal.
"If we have a tumor, these probes should have the ability to latch on to it," Irudayaraj said. "The
probe could carry drugs to target, treat as well as reveal cancer cells."
Scientists have developed probes that use gold nanorods or magnetic particles, but
Irudayaraj's nanoprobes use both, making them easier to track with different imaging devices
as they move toward cancer cells.
The magnetic particles can be traced through the use of an MRI machine, while the gold
nanorods are luminescent and can be traced through microscopy, a more sensitive and
precise process. Irudayaraj said an MRI is less precise than optical luminescence in tracking
the probes, but has the advantage of being able to track them deeper in tissue, expanding the
probes' possible applications.
The probes, which are about 1,000 times smaller than the diameter of a human hair, contain
the antibody Herceptin, used in treatment of metastatic breast cancer. The probes would be
injected into the body through a saline buffering fluid, and the Herceptin would find and attach
to protein markers on the surface of cancer cells.
103
"When the cancer cell expresses a protein marker that is complementary to Herceptin, then it
binds to that marker," Irudayaraj said. "We are advancing the technology to add other drugs
that can be delivered by the probes."
Irudayaraj said better tracking of the nanoprobes could allow doctors to pinpoint the location of
known tumors and better treat the cancer.
The novel probes were tested in cultured cancer cells. Irudayaraj said the next step would be
to run a series of tests in mice models to determine the dose and stability of the probes.
The research was funded through a National Institute of Health grant, as well as by the Purdue
Research Foundation. Irudayaraj is head of a biological engineering team that includes
postdoctoral researcher Chungang Wang and graduate student Jiji Chen.
3 月 17 日
Increase Risk Of Blood Disorders Due To Genetic Abnormality
Researchers at Memorial Sloan-Kettering Cancer Center (MSKCC) have shown for the first
time that a tendency to develop some blood disorders may be inherited. Their research,
published online in Nature Genetics, identifies a common genetic sequence abnormality that
enhances the likelihood of acquiring a mutation in a gene linked to certain blood diseases.
The investigators carried out a genome-wide study to identify inherited DNA sequence
changes that frequently occur in patients with myeloproliferative neoplasms, in which several
types of blood cells are excessively produced in the bone marrow. They found that an inherited
alteration in the gene for JAK2 - a protein with enzymatic activity that is linked to the abnormal
production of blood cells - is more common in patients with these disorders. Importantly,
patients who inherited this JAK2 alteration were predisposed to acquiring another JAK2
mutation on the same DNA strand. According to the research, these mutations do not arise
randomly, but are specifically determined by the DNA sequence.
More than half of patients afflicted with myeloproliferative neoplasms - which affect an
estimated 140,000 people in the US - carry the JAK2 mutation and suffer from the
overproduction of red blood cells, platelets, or fibrous connective tissue. According to the
authors, understanding the underlying inherited sequence partly explains the predisposition for
acquiring mutations in certain disease-specific genes and may help explain why some
individuals are at higher risk in developing the disease.
3 月 17 日
Clinical Trial To Improve Outcomes In Patients With Breast Cancer
Now Open
Researchers at The Cancer Institute of New Jersey (CINJ) have opened a clinical trial, which
aims to evaluate a new treatment for breast cancer in combination with one that is already
approved for other types cancers. The new combination is targeted toward treatment of
hormone receptor-positive locally advanced cancer (cancer cells that grow and multiply when
the estrogen hormone attaches to the hormone receptor) or metastatic breast cancer (cancer
that spreads to other parts of the body). CINJ is a center of excellence of UMDNJ-Robert
104
Wood Johnson Medical School.
According to the American Cancer Society, excluding skin cancer, breast cancer is the most
frequently diagnosed cancer in women. In 2008, it was estimated that more than 182,000
women were diagnosed with breast cancer in the United States, while more than 40,000 died
from the disease. In New Jersey, there were 6,300 new cases were expected with
approximately 1,400 deaths. That is why CINJ investigators are testing the effectiveness of the
drug sorafenib in combination with letrozole.
Sorafenib is an approved medication by the U.S. Food and Drug Administration (FDA) used to
treat certain advanced kidney cancers and liver cancer. It fights the disease by interfering with
the ability of cancer cells to grow and divide. There have been studies performed with this
drug by itself in patients with metastatic breast cancer, with results showing only a small effect
on the tumor.
But according to Antoinette Tan, MD, a medical oncologist at CINJ and assistant professor of
medicine at UMNDJ-Robert Wood Johnson Medical School, there is a lot of potential for
sorafenib to be combined with letrozole, a drug which blocks enzymes that make the estrogen
hormone. Letrozole received FDA approval in 2001 for the treatment of patients with
metastatic breast cancer. It has been shown to be more effective than the drug tamoxifen,
which is commonly used for treatment, and to have fewer side effects than other medications
used in hormonal therapy. Dr. Tan is the lead researcher on the new study.
Selected patients will take letrozole and sorafenib by mouth and keep a pill diary for 28
days. At 12 weeks, patients will undergo tests like a CT scan or MRI, which look at the organs
in the body, to check on the combined effect on the tumor. The aforementioned drugs for the
study will be supplied by Bayer Pharmaceuticals and Novartis Pharmaceuticals.
Women over age 18, who are post-menopausal and have the diagnosis of hormone
receptor-positive locally advanced or metastatic breast cancer are eligible to take part in the
trial, although other criteria must be met. The study is part of the CINJ Oncology Group
(CINJOG), which is comprised of physicians throughout New Jersey from the CINJ Network of
hospitals.
Clinical trials, often called cancer research studies, test new treatments and new ways of
using existing treatments for cancer. At CINJ, researchers use these studies to answer
questions about how a treatment affects the human body and to make sure it is safe and
effective. There are several types of clinical trials that are currently underway at CINJ,
including those that diagnose, treat, prevent, and manage symptoms of cancer. Many
treatments used today, whether it is drugs or vaccines; ways to do surgery or give radiation
therapy; or combinations of treatments, are the results of past clinical trials.
As New Jersey's only National Cancer Institute-designated Comprehensive Cancer Center,
CINJ offers patients access to treatment options not available at other institutions within the
105
state. CINJ currently enrolls more than 1,000 patients on clinical trials, including
approximately 15 percent of all new adult cancer patients and approximately 70 percent of all
pediatric cancer patients. Enrollment in these studies nationwide is fewer than five percent of
all adult cancer patients.
About The Cancer Institute of New Jersey
The Cancer Institute of New Jersey is the state's first and only National Cancer
Institute-designated Comprehensive Cancer Center, and is dedicated to improving the
prevention, detection, treatment and care of patients with cancer. CINJ's physician-scientists
engage in translational research, transforming their laboratory discoveries into clinical practice,
quite literally bringing research to life. The Cancer Institute of New Jersey is a center of
excellence of UMDNJ-Robert Wood Johnson Medical School. To support CINJ, please call
the Cancer Institute of New Jersey Foundation at 1-888-333-CINJ.
The Cancer Institute of New Jersey Network is comprised of hospitals throughout the state and
provides a mechanism to rapidly disseminate important discoveries into the community.
Flagship Hospital: Robert Wood Johnson University Hospital. Major Clinical Research Affiliate
Hospitals: Carol G. Simon Cancer Center at Morristown Memorial Hospital, Carol G. Simon
Cancer Center at Overlook Hospital, Jersey Shore University Medical Center. Affiliate
Hospitals: Bayshore Community Hospital, CentraState Healthcare System, Cooper University
Hospital*, JFK Medical Center, Raritan Bay Medical Center, Robert Wood Johnson University
Hospital at Hamilton (CINJ at Hamilton), Saint Peter's University Hospital, Somerset Medical
Center, Southern Ocean County Hospital, The University Hospital/UMDNJ-New Jersey
Medical School*, and University Medical Center at Princeton. *Academic Affiliate
Source
Cancer Institute of New Jersey
3 月 17 日
Studying The Viscosity Of Cancer Cells During Cell Death
The viscosity, or 'gloopiness', of different parts of cancer cells increases dramatically when
they are blasted with light-activated cancer drugs, according to new images that provide
fundamental insights into how cancer cells die, published in Nature Chemistry.
The images reveal the physical changes that occur inside cancer cells whilst they are dying as
a result of Photodynamic Therapy (PDT). This cancer treatment uses light to activate a drug
that creates a short-lived toxic type of oxygen, called singlet oxygen, which kills cancerous
cells.
The research team behind the study says that revealing what happens to viscosity within a
dying cancer cell is important because it helps give a better understanding of how cells
function and which factors are important for controlling reactions inside cells. Ultimately this
could help scientists design more efficient drugs for Photodynamic Therapy and other
106
treatments.
The research is also of wider significance because these are the first ever real-time maps
showing viscosity changing over a period of time inside a cell during a biologically important
process like cell death.
Previous studies have shown that the viscosity of human cells and organs also changes in
patients with diseases including diabetes and atherosclerosis, says lead author Dr Marina
Kuimova from Imperial College London's Department of Chemistry.
She explains: "We're still not quite sure exactly what the relationship is between increased
stickiness inside cells and disease, but we expect that the two are related."
"Knowing more about these changes, and being able to map them when they occur in all kinds
of different scenarios, from dying cancer cells, to diseased blood cells, could help us to better
understand how some diseases and their treatments affect cell and organ function."
Dr Kuimova and her colleagues were able to track viscosity as it changed inside live cancer
cells thanks to a newly-developed Photodynamic Therapy drug, with unusual fluorescent
properties. The drug, which is made of a molecule with a spinning component like a rotor,
emits different wavelengths of light depending on the viscosity of its surroundings.
The changing wavelengths of light emitted during experiments, and captured over a period of
10 minutes, showed that once the PDT drug was activated, the level of viscosity inside the cell
increased dramatically. The researchers suggest that this increasing 'gloopiness' is caused by
the toxic oxygen molecules released into the cell. They think that increased levels of viscosity
might even contribute directly to the cancer cell's further deterioration by slowing down vital
communication and transport processes inside the cell.
Dr Stanley Botchway from the Science and Technology Facilities Council which worked in
collaboration with Imperial College London on this research, said: "The huge viscosity we
measured was surprising and it certainly gives a new insight into the change in cellular
environment during cell death."
However, the researchers noted that as viscosity in the cancerous cell increases, the toxic
oxygen molecule's mission to kill the cell is slowed down too.
Dr Kuimova explains: "It looks like whilst the increasing viscosity contributes to the cell's
demise, these new 'sticky' cell conditions can slow the drug down too, so it's not as
straightforward a relationship as it might first appear.
"More work is needed to better understand the complex interplay between viscosity and cell
death. We hope to use our imaging technique to track changes in viscosity in other kinds of
cells as they occur in real-time, to unlock some of the secrets of what goes on inside cells
107
when they're functioning, malfunctioning or dying."
---------------------------Article adapted by Medical News Today from original press release.
---------------------------The research was led by Imperial College London in collaboration with the Science and
Technology Facilities Council's Rutherford Appleton Laboratory (RAL), the University of Oxford,
King's College London, and the University of Aarhus in Denmark. The work was funded by the
Engineering and Physical Sciences Research Council, with support from the Science and
Technology Facilities Council, and the Danish Foundation for Basic Research.
Source: Danielle Reeves
Imperial College London
3 月 17 日
Studying The Viscosity Of Cancer Cells During Cell Death
The viscosity, or 'gloopiness', of different parts of cancer cells increases dramatically when
they are blasted with light-activated cancer drugs, according to new images that provide
fundamental insights into how cancer cells die, published in Nature Chemistry.
The images reveal the physical changes that occur inside cancer cells whilst they are dying as
a result of Photodynamic Therapy (PDT). This cancer treatment uses light to activate a drug
that creates a short-lived toxic type of oxygen, called singlet oxygen, which kills cancerous
cells.
The research team behind the study says that revealing what happens to viscosity within a
dying cancer cell is important because it helps give a better understanding of how cells
function and which factors are important for controlling reactions inside cells. Ultimately this
could help scientists design more efficient drugs for Photodynamic Therapy and other
treatments.
The research is also of wider significance because these are the first ever real-time maps
showing viscosity changing over a period of time inside a cell during a biologically important
process like cell death.
Previous studies have shown that the viscosity of human cells and organs also changes in
patients with diseases including diabetes and atherosclerosis, says lead author Dr Marina
Kuimova from Imperial College London's Department of Chemistry.
She explains: "We're still not quite sure exactly what the relationship is between increased
stickiness inside cells and disease, but we expect that the two are related."
"Knowing more about these changes, and being able to map them when they occur in all kinds
108
of different scenarios, from dying cancer cells, to diseased blood cells, could help us to better
understand how some diseases and their treatments affect cell and organ function."
Dr Kuimova and her colleagues were able to track viscosity as it changed inside live cancer
cells thanks to a newly-developed Photodynamic Therapy drug, with unusual fluorescent
properties. The drug, which is made of a molecule with a spinning component like a rotor,
emits different wavelengths of light depending on the viscosity of its surroundings.
The changing wavelengths of light emitted during experiments, and captured over a period of
10 minutes, showed that once the PDT drug was activated, the level of viscosity inside the cell
increased dramatically. The researchers suggest that this increasing 'gloopiness' is caused by
the toxic oxygen molecules released into the cell. They think that increased levels of viscosity
might even contribute directly to the cancer cell's further deterioration by slowing down vital
communication and transport processes inside the cell.
Dr Stanley Botchway from the Science and Technology Facilities Council which worked in
collaboration with Imperial College London on this research, said: "The huge viscosity we
measured was surprising and it certainly gives a new insight into the change in cellular
environment during cell death."
However, the researchers noted that as viscosity in the cancerous cell increases, the toxic
oxygen molecule's mission to kill the cell is slowed down too.
Dr Kuimova explains: "It looks like whilst the increasing viscosity contributes to the cell's
demise, these new 'sticky' cell conditions can slow the drug down too, so it's not as
straightforward a relationship as it might first appear.
"More work is needed to better understand the complex interplay between viscosity and cell
death. We hope to use our imaging technique to track changes in viscosity in other kinds of
cells as they occur in real-time, to unlock some of the secrets of what goes on inside cells
when they're functioning, malfunctioning or dying."
---------------------------Article adapted by Medical News Today from original press release.
---------------------------The research was led by Imperial College London in collaboration with the Science and
Technology Facilities Council's Rutherford Appleton Laboratory (RAL), the University of Oxford,
King's College London, and the University of Aarhus in Denmark. The work was funded by the
Engineering and Physical Sciences Research Council, with support from the Science and
Technology Facilities Council, and the Danish Foundation for Basic Research.
Source: Danielle Reeves
Imperial College London
109
3 月 17 日
Early Detection Remains Key In Updated NCCN Guidelines For
Ovarian Cancer
Improvements in screening and early detection remains the key for women with ovarian
cancer according to Robert J. Morgan, MD, of City of Hope Comprehensive Cancer Center
and chair of the NCCN Guidelines Panel for Ovarian Cancer. Dr. Morgan discussed the future
of ovarian cancer and notable changes to the recently updated NCCN Clinical Practice
Guidelines in Oncology(TM) for Ovarian Cancer at the NCCN Annual Conference on Saturday,
March 14.
Dr. Morgan began by explaining that the major challenge in treating ovarian cancer is that by
the time the majority of patients (70 percent) are diagnosed with the disease, it has already
progressed to stage III or IV. "We have not yet found a good way to screen the general
population or even the high-risk population of women for ovarian cancer," he said.
New to the NCCN Guidelines is a section on the management of allergic reactions in patients
receiving chemotherapy for ovarian cancer. Dr. Morgan explained the need for this section as
ovarian cancer tends to respond to the same treatment repeatedly. Combined with the fact that
recurrence rates of ovarian cancer are high, this can result in patients often being retreated
with the same chemotherapeutic agent. Given that virtually all chemotherapy drugs have the
potential to cause infusion reactions, including agents commonly used in ovarian cancer, the
NCCN Guidelines Panel felt it was important to provide information on allergic reactions and
recommendations on desensitization regimens.
"Most patients experiencing allergic reactions are able to be desensitized allowing for
continued chemotherapeutic treatment, which is vital to the management of ovarian cancer,"
said Dr. Morgan.
Also new to the updated NCCN Guidelines is the addition of new agents for recurrence therapy,
most notably pemetrexed (Alimta(R), Eli Lilly and Company) as well as recommendations for
therapies based on the timing of recurrence.
"Seventy-five to 80 percent of patients with stage III or IV ovarian cancer will experience
recurrence and this recurrence can occur at any time - during treatment, within 6 months of
completing treatment, or more than a year after completing treatment," Dr. Morgan noted. "In
the updated NCCN Guidelines, we differentiated appropriate therapy for recurrence based
upon the time frame on which it occurs."
Additionally, Dr. Morgan referred to a clinical trial suggesting that pemetrexed is active in
recurrent ovarian cancer, to support the new recommendation in the updated NCCN
Guidelines.
Dr. Morgan described new updates to the Principles of Primary Surgery section in the updated
110
NCCN Guidelines that included the recommendation to consider completion surgery for
patients responsive to chemotherapy with initially unresectable residual disease, as well as
recommendations relating to special circumstances including minimally-invasive procedures,
and fertility sparing procedures.
Dr. Morgan also discussed recent clinical studies conducted abroad that studied the effect of
chemotherapy as an up-front therapy in patients with ovarian cancer, and concluded that "in
the United States, up-front debulking surgery remains the recommendation for the best overall
survival."
Another addition to the updated NCCN Guidelines is a section on the Principles of
Chemotherapy. This section emphasizes the encouragement of patients participating in clinical
trials during all aspects of their treatment course as well as noting that patients with newly
diagnosed tumors should be informed about the different options available, particularly IV vs.
IV/IP chemotherapy and the risks and benefits of each regimen.
"The future of ovarian cancer lies in early detection and improvements in screening," Dr.
Morgan noted as he discussed potential biomarkers for the detection, prediction and
prognostication of ovarian cancer.
He concluded that steady progress is being made in the treatment of ovarian cancer, but
further trials are necessary to investigate the role of targeted agents alone and in combination
in newly diagnosed and recurrent ovarian cancer. Finally, he again stressed the need for
physicians to encourage their patients to participate in clinical trials.
About the National Comprehensive Cancer Network
The National Comprehensive Cancer Network (NCCN), a not-for-profit alliance of 21 of the
world's leading cancer centers, is dedicated to improving the quality and effectiveness of care
provided to patients with cancer. Through the leadership and expertise of clinical professionals
at NCCN Member Institutions, NCCN develops resources that present valuable information to
the numerous stakeholders in the health care delivery system. As the arbiter of high-quality
cancer care, NCCN promotes the importance of continuous quality improvement and
recognizes the significance of creating clinical practice guidelines appropriate for use by
patients, clinicians, and other health care decision-makers. The primary goal of all NCCN
initiatives is to improve the quality, effectiveness, and efficiency of oncology practice so
patients can live better lives.
The NCCN Member Institutions are: City of Hope Comprehensive Cancer Center, Los Angeles,
CA; Dana-Farber/Brigham and Women's Cancer Center | Massachusetts General Hospital
Cancer Center, Boston, MA; Duke Comprehensive Cancer Center, Durham, NC; Fox Chase
Cancer Center, Philadelphia, PA; Huntsman Cancer Institute at the University of Utah, Salt
Lake City, UT; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance,
Seattle, WA; Arthur G. James Cancer Hospital & Richard J. Solove Research Institute at The
111
Ohio State University, Columbus, OH; The Sidney Kimmel Comprehensive Cancer Center at
Johns Hopkins, Baltimore, MD; Robert H. Lurie Comprehensive Cancer Center of
Northwestern University, Chicago, IL; Memorial Sloan-Kettering Cancer Center, New York, NY;
H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; Roswell Park Cancer Institute,
Buffalo, NY; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University
School of Medicine, St. Louis, MO; St. Jude Children's Research Hospital/University of
Tennessee Cancer Institute, Memphis, TN; Stanford Comprehensive Cancer Center, Stanford,
CA; University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL;
UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of
Michigan Comprehensive Cancer Center, Ann Arbor, MI; UNMC Eppley Cancer Center at The
Nebraska Medical Center, Omaha, NE; The University of Texas M. D. Anderson Cancer Center,
Houston, TX; and Vanderbilt-Ingram Cancer Center, Nashville, TN.
For more information on NCCN, please visit http://www.nccn.org.
National Comprehensive Cancer Network
3 月 17 日
Master Molecular Switch May Prevent The Spread Of Cancer Cells
To Distant Sites In The Body
Researchers at the University of Pennsylvania School of Medicine have identified a master
switch that might prevent cancer cells from metastasizing from a primary tumor to other organs.
The switch is a protein that, when in the "on" position, maintains the normal character of cells
that line the surface of organs and body cavities. These epithelial cells are the type of cell from
which most solid tumors arise. However, when the switch is turned "off" or absent, epithelial
cells acquire characteristics of another cell type, called mesenchymal cells, and gain the ability
to migrate and move away from the primary tumor. The researchers report their findings in this
month's issue of Molecular Cell.
Understanding how this switch works may one day lead to a drug that controls cancer cell
metastasis and tissue fibrosis.
This change in cell motility is called the epithelial to mesenchymal transition, or EMT, and is an
important process during the development of embryos. But when the transition is aberrantly
reactivated in adults it can have dire physiological consequences, leading to cancer
metastasis as well as other disease processes such as tissue fibrosis. Fibrotic tissue is a
hallmark of organ failure, as in liver cirrhosis or kidney failure.
The master-switch is called the Epithelial Splicing Regulatory Protein, and comes in two
closely related versions, ESRP1 and ESRP2. These proteins are able to change how RNAs
that are produced from genes are spliced together. This is achieved by splicing different exons
-- the sequence of DNA that codes information for protein synthesis -- together in different
ways so that there can be more than one messenger RNA (mRNA) produced from the same
gene. These mRNAs then go on to make different proteins.
112
The mRNA for Fibroblast Growth Factor Receptor 2 (FGFR2) is the focus of the Molecular Cell
study. FGFR2 mRNA has two forms, one called IIIb, which is expressed in epithelial cells and
IIIc, which is expressed in mesenchymal cells. The protein that is made from the IIIb form
interacts with factors outside the cell that promote the epithelial cell behavior, that is to remain
stationary. When the IIIc form is aberrantly produced in cancer cells derived from epithelial
cells, the resulting FGFR2 protein type no longer promotes the epithelial cell identity, and
switches to the mesenchymal cell type, which has the ability to detach from its primary site,
invade local tissue and migrate, or metastasize to distant sites of the body.
"If we can find a way to maintain expression of ESRP1 and 2 in epithelial cells, then it might be
possible to prevent metastasis or control fibrosis," notes corresponding author Russ P.
Carstens, MD, Assistant Professor of Medicine. "ESRP1 and ESRP2 are necessary for
splicing FGFR2 mRNA in the epithelial cell manner. This is one of few known splicing factors
that operate in a clear cut cell-type-specific manner. Epithelial cells, which make up the lining
of organs, are the only cells that produce ESRP1 and ESRP2."
To discover ESRP1 and ESRP2, the team used a high-throughput genetic screen for rare
proteins developed by collaborator and co-author John B. Hogenesch, PhD, Associate
Professor of Pharmacology, an innovator in the use of these types of screens. In addition,
Claude Warzecha, a graduate student in the Carstens lab, played a key role in the completion
of the screen.
The screen consists of about 15,000 different cDNAs (DNA that has been synthesized from
messenger RNAs) that each express a different gene and are arrayed on plates so that each
well of the plate expresses only one individual gene product. The Carstens lab developed a
splicing "reporter" that makes cells express a firefly luciferase gene and "glow" when it is
spliced in the epithelial cell pattern. Cells with this reporter were individually placed over wells
containing each cDNA and cells that "glowed, indicated those cDNAs that produced proteins
that promoted the epithelial splicing program. It was from this screen that ESRP1 and ESRP2
emerged.
In ongoing work, the team found that ESRP1 and ESRP2 are critical for epithelial-specific
splicing of many other genes in addition to FGFR2. Several of the proteins made from these
RNAs also have different functions that either help cells to stay attached in place or to promote
local invasion of cancer cells that are capable of traveling to distant sites. The team is also
engineering mice in which the genes for ESRP1 and 2 can be selectively "knocked-out" so that
they can further study the importance of these two proteins during development as well as in
disease. In addition, studies are planned to use the same splicing reporter system to screen
for drugs that might restore the epithelial pathway and interfere with metastasis and fibrosis.
This work was supported by the Pennsylvania Department of Health, the National Cancer
Institute, the Department of Defense, and the Penn Genome Frontiers Institute. Additional
team members included Behnam Nabet in the Carstens lab and Trey K. Sato from the
113
Hogenesch lab.
PENN Medicine is a $3.6 billion enterprise dedicated to the related missions of medical
education, biomedical research, and excellence in patient care. PENN Medicine consists of
the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first
medical school) and the University of Pennsylvania Health System.
Penn's School of Medicine is currently ranked #4 in the nation in U.S.News & World Report's
survey of top research-oriented medical schools; and, according to most recent data from the
National Institutes of Health, received over $379 million in NIH research funds in the 2006
fiscal year. Supporting 1,700 fulltime faculty and 700 students, the School of Medicine is
recognized worldwide for its superior education and training of the next generation of
physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System (UPHS) includes its flagship hospital, the
Hospital of the University of Pennsylvania, rated one of the nation's top ten "Honor Roll"
hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and
Penn Presbyterian Medical Center. In addition UPHS includes a primary-care provider network;
a faculty practice plan; home care, hospice, and nursing home; three multispecialty satellite
facilities; as well as the Penn Medicine at Rittenhouse campus, which offers comprehensive
inpatient rehabilitation facilities and outpatient services in multiple specialties.
University of Pennsylvania School of Medicine
3535 Market St., Mezzanine
Philadelphia
PA 19104
United States
3 月 17 日
New Research Gives Hope For Breakthrough Cancer Treatment
New research into the interaction between normal cells and transformed cells has given hope
to uncovering an effective treatment for cancer.
A study funded by the Medical Research Council, available online and due to be published in
Nature Cell Biology in April, examined the boundary between normal cells and transformed
cells (transformed cells can result in cancer). The results showed that transformed cells
change their shape and are removed from the tissues when surrounded by normal cells.
Lead author Yasuyuki Fujita, from the MRC Laboratory for Molecular Cell Biology at University
College London, said: "The research could help us understand how cancer initiates and
develops, and further studies into this behaviour could help find ways of treating cancer
effectively."
Scientists also identified signalling pathways which are activated in transformed cells when
114
surrounded by normal cells, but not when they were surrounded by other transformed cells.
The activity in the transformed cells and the cell-to-cell contact with surrounding normal cells
influenced the way the transformed cells behaved.
Dr Fujita said: "It is not clear how these signalling pathways that regulate cells' behaviour are
activated in transformed cells or how transformed cells can sense the differences in normal
cells. This will require further investigation. Our findings, however, show that transformed cells
are excluded, either apically or basally, from a monolayer of surrounding normal cells. When
the transformed cells are basally excluded, the cancer spreads; when they are apically
excluded, the progression of cancer stops - the result we were seeking."
The research is novel in that the scientists focused on the interaction between normal and
transformed cells. In the past most research has focused only on transformed cancer cells and
overlooked the fact that mutations occur in a cell which is surrounded by normal cells.
"By further studying molecular mechanisms involved, we may be able to invent a novel type of
cancer treatment to exclude cancer cells from the body using the help of surrounding normal
cells," Dr Fujita said.
Notes
Characterization of the interface between normal and transformed epithelial cells is published
online DOI: 10.1038/ncb1853
The Medical Research Council supports the best scientific research to improve human health.
Its work ranges from molecular level science to public health medicine and has led to
pioneering discoveries in our understanding of the human body and the diseases which affect
us all.
Founded in 1826, University College London was the first English university established after
Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender,
and the first to provide systematic teaching of law, architecture and medicine. UCL is the
seventh-ranked university in the 2008 THES-QS World University Rankings, and the
third-ranked UK university in the 2008 league table of the top 500 world universities produced
by the Shanghai Jiao Tong University. UCL alumni include Marie Stopes, Jonathan Dimbleby,
Lord Woolf, Alexander Graham Bell, and members of the band Coldplay. UCL currently has
over 12,000 undergraduate and 8,000 postgraduate students. Its annual income is over £600
million.
Source
Medical Research Council
3 月 17 日
115
NCCN Presents Updates To NCCN Guidelines For Thyroid
Carcinoma
The incidence of thyroid carcinoma is increasing faster than any other solid tumor according to
Steven I. Sherman, MD, of The University of Texas M.D. Anderson Cancer Center during a
recent presentation at the National Comprehensive Cancer Network's 14th Annual Conference
discussing updates to the NCCN Clinical Practice Guidelines in Oncology(TM) for Thyroid
Carcinoma.
"The increasing incidence of thyroid carcinoma is a worldwide phenomenon," stated Dr.
Sherman as he outlined major updates to the NCCN Guidelines.
A notable addition to the NCCN Guidelines is a recommendation to consider commercially
available, small molecule kinase inhibitors such as sorafenib (Nexavar(R), Bayer) or sunitinib
(Sutent(R), Pfizer, Inc.) in the treatment of metastatic papillary carcinoma, follicular carcinoma,
Hurthle cell carcinoma, or medullary carcinoma.
"Our primary recommendation for these patients is to investigate a clinical trial, but if one is not
available or appropriate; data from clinical trials have shown that small molecule kinase
inhibitors such as sorafenib and sunitinib can be effective," said Dr. Sherman.
Also new to the NCCN Guidelines is a page, Principles of Thyroid Stimulating Hormone (TSH)
Suppression that provides recommendations for levothyroxine use for TSH Suppression
throughout the Papillary, Follicular and Hurthle Cell Guidelines.
"Given the potential toxicities associated with TSH Suppression therapy that can have an
effect on bone and heart health, it is best to use this therapy in a limited capacity," noted
Sherman. "The new page in the NCCN Guidelines states that patients should be treated with
the most conservative dose of hormone suppression therapy based on their level of disease
plan. In addition, for those patients with recurrent thyroid carcinoma being administered TSH
therapy, the NCCN Guidelines recommend decreasing the dose over time and encouraging
adequate intake of calcium and vitamin D to prevent osteoporosis."
In addition, the procedures for evaluating thyroid nodules have been revised in the updated
NCCN Guidelines particularly those for follicular or Hurthle cell neoplasms or for follicular
lesions of undetermined significance, which cannot be diagnosed by fine needle aspiration
(FNA). The diagnostic categories for FNA results have been revised in the new NCCN
Guidelines and reflect recent data from the National Cancer Institute State of the Science
Conference.
Dr. Sherman stressed the importance of evaluating suspicious nodules saying that,
"ultrasound continues to be the single most useful imaging tool to diagnose palpable thyroid
masses, however; there are no diagnostic features of a nodule that is benign."
116
About the National Comprehensive Cancer Network
The National Comprehensive Cancer Network (NCCN), a not-for-profit alliance of 21 of the
world's leading cancer centers, is dedicated to improving the quality and effectiveness of care
provided to patients with cancer. Through the leadership and expertise of clinical professionals
at NCCN Member Institutions, NCCN develops resources that present valuable information to
the numerous stakeholders in the health care delivery system. As the arbiter of high-quality
cancer care, NCCN promotes the importance of continuous quality improvement and
recognizes the significance of creating clinical practice guidelines appropriate for use by
patients, clinicians, and other health care decision-makers. The primary goal of all NCCN
initiatives is to improve the quality, effectiveness, and efficiency of oncology practice so
patients can live better lives.
The NCCN Member Institutions are: City of Hope Comprehensive Cancer Center, Los Angeles,
CA; Dana-Farber/Brigham and Women's Cancer Center | Massachusetts General Hospital
Cancer Center, Boston, MA; Duke Comprehensive Cancer Center, Durham, NC; Fox Chase
Cancer Center, Philadelphia, PA; Huntsman Cancer Institute at the University of Utah, Salt
Lake City, UT; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance,
Seattle, WA; Arthur G. James Cancer Hospital & Richard J. Solove Research Institute at The
Ohio State University, Columbus, OH; The Sidney Kimmel Comprehensive Cancer Center at
Johns Hopkins, Baltimore, MD; Robert H. Lurie Comprehensive Cancer Center of
Northwestern University, Chicago, IL; Memorial Sloan-Kettering Cancer Center, New York, NY;
H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; Roswell Park Cancer Institute,
Buffalo, NY; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University
School of Medicine, St. Louis, MO; St. Jude Children's Research Hospital/University of
Tennessee Cancer Institute, Memphis, TN; Stanford Comprehensive Cancer Center, Stanford,
CA; University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL;
UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of
Michigan Comprehensive Cancer Center, Ann Arbor, MI; UNMC Eppley Cancer Center at The
Nebraska Medical Center, Omaha, NE; The University of Texas M. D. Anderson Cancer Center,
Houston, TX; and Vanderbilt-Ingram Cancer Center, Nashville, TN.
For more information on NCCN, please visit http://www.nccn.org.
National Comprehensive Cancer Network
3 月 17 日
Penn Researchers Identify New Protein Important in Breast Cancer Gene’s Role in DNA Repair
PHILADELPHIA – For years, researchers have known that under normal conditions, the breast cancer
protein BRCA1 orchestrates the repair of damaged DNA, but the details of just how BRCA1 moves to the
damaged site and recruits the right nuclear repairmen for DNA restoration remains a mystery.
Now, a new study from the University of Pennsylvania School of Medicine
has identified genes associated with the BRCA1 protein and their
involvement in the DNA repair pathway, helping to clear the way for
117
researchers to better understand what goes wrong when the BRCA1 gene is
mutated and the repair pathway goes haywire. Identifying patients with
mutations in these BRCA1-associated genes may help better fight breast
cancer.
The new study appears in the most recent issue of Genes & Development.
“A mutated BRCA1 gene increases vulnerability to breast and ovarian
cancers by increasing the rate at which genes are altered,” says Roger
Greenberg, MD, PhD, Assistant Professor of Cancer Biology at the Abramson
Family Cancer Research Institute at the University of Pennsylvania.
Previous studies have shown that mutated BRCA1-associated proteins also
increase the risk of breast cancer, implying that a BRCA1-centered DNA
repair pathway is necessary to suppress cancer.
About two years ago, Greenberg helped to lead a study that identified the
role of a BRCA1-associated protein called RAP80. The BRCA1 protein works
in partnership with RAP80 to locate damaged DNA sites. Cancer-causing
mutant BRCA1 proteins fail to pair up with RAP80, which, in turn, blinds
BRCA1 to DNA damage. The results of the study led Greenberg’s group to
look closer at the interaction between BRCA1 and RAP80 to learn the
molecular details of how this complex functioned in DNA repair and to
explore RAP80 as a possible breast-cancer-susceptibility gene candidate.
In the latest study, Greenberg’s team returned to the BRCA1-RAP80 complex
for additional analysis, and identified another protein called MERIT40
that works with BRCA1-RAP80 to achieve DNA repair. MERIT40, a previously
unknown protein, was revealed by purifying BRCA1-RAP80 complexes from
human cells. MERIT40 not only recruits BRCA1 and RAP80 to the sites of
DNA damage and signals for DNA repairman to the site, but also acts as
the molecular scaffold for the BRCA1-RAP80 complex.
“The BRCA1-RAP80 protein complex works as machine. If a piece of the
machine is missing, the machine will begin to break down and eventually
stop working,” says Greenberg. Without MERIT40, Greenberg’s group
discovered that the BRCA1-RAP80 complex degrades, denying BRCA1 access
to the DNA damage sites within the genome.
The identification of MERIT40 as a BRCA1-associated gene may also lead
researchers to other genes that increase vulnerability to breast cancer.
Greenberg said the identification of the fundamental role of RAP80 several
years ago has led researchers to explore RAP80 as a cancer-causing gene.
Greenberg said ongoing studies have confirmed that mutations to the RAP80
gene occur in human populations and may cause cancer. These reports will
be published later this year, he said.
118
“There are many genes associated with BRCA1 that turn out to be mutated
in breast cancer,” Greenberg said. “MERIT40 now becomes another good
gene to study.”
Understanding how BRCA responds to damaged DNA can also help scientists
to better fight cancer with chemotherapy, notes Greenberg. By shutting
MERIT40 genes off, researchers may be able to weaken cancer cells, leaving
them more susceptible to attack by chemotherapy.
In the future, Greenberg says he hopes to gain a better understanding of
how MERIT40 works by looking for MERIT40 mutations in breast cancer
patients.
The National Cancer Institute, the Sidney Kimmel Foundation Scholar Award,
The Mary Kay Ash Foundation Translational Innovation Award and the
Abramson Family Cancer Research Institute funded this research.
Study co-authors include: Genze Shao, Jeffrey Patterson-Fortin, Troy E.
Messick, Dan Feng, Niraj Shanbhag and Yingqun Wang, all from Penn.
###
PENN Medicine is a $3.6 billion enterprise dedicated to the related
missions of medical education, biomedical research, and excellence in
patient care. PENN Medicine consists of the University of Pennsylvania
School of Medicine (founded in 1765 as the nation's first medical school)
and the University of Pennsylvania Health System.
Penn's School of Medicine is currently ranked #4 in the nation in U.S.News
& World Report's survey of top research-oriented medical schools; and,
according to most recent data from the National Institutes of Health,
received over $379 million in NIH research funds in the 2006 fiscal year.
Supporting 1,700 fulltime faculty and 700 students, the School of Medicine
is recognized worldwide for its superior education and training of the
next generation of physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System (UPHS) includes its flagship
hospital, the Hospital of the University of Pennsylvania, rated one of
the nation’s top ten “Honor Roll” hospitals by U.S.News & World Report;
Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian
Medical Center. In addition UPHS includes a primary-care provider network;
a faculty practice plan; home care, hospice, and nursing home; three
multispecialty satellite facilities; as well as the Penn Medicine at
Rittenhouse campus, which offers comprehensive inpatient rehabilitation
facilities and outpatient services in multiple specialties.
119
3 月 18 日
Researchers identify genetic markers for aggressive
head and neck cancer
Specific microRNA levels may predict poor prognosis
March 18, 2009 – (BRONX, NY) – Scientists at Albert Einstein College
of Medicine of Yeshiva University have identified genetic markers that
signal poor outcomes for patients with head and neck cancer. These
findings could one day lead to a genetic test that could help select or
predict successful treatment options for patients with this type of cancer.
The results were published in the American Journal of Pathology.
Head and neck cancer refers to tumors in the mouth, throat or larynx (voice
box). Each year, about 40,000 men and women in the U.S. develop head and
neck cancer, making it the sixth most common cancer in the U.S. Surgery,
chemotherapy and/or radiation are the main treatment options but cause
serious side effects: surgery may involve removing large areas of the
tongue, throat, or neck and can affect appearance, and any type of therapy
can cause swallowing or speech problems that can significantly affect
quality of life. Despite curative treatment attempts, on average only
about half of patients survive beyond five years after treatment. This
is greatly affected by the size and location of the tumor.
The Einstein study focuses on microRNAs, a recently identified class of
short RNA molecules that play key roles in regulating gene expression.
Abnormal microRNA levels have been associated with all types of cancer
yet examined.
120
In previous research, the Einstein scientists and other groups reported
that approximately 50 specific microRNAs were expressed at higher or lower
levels in head and neck tumor cell lines compared with normal cells. In
this study, the Einstein researchers, for the first time, have linked
levels of specific microRNAs with tumor recurrence and poorer survival
in head and neck cancer.
The Einstein team analyzed samples from 104 head and neck cancer patients
from Montefiore Medical Center, The University Hospital and Academic
Medical Center for Einstein. The patients were treated and followed over
five years. At the time of cancer diagnosis and before any therapy,
researchers removed samples tumor tissue from patients, as well as normal
tissue adjacent to their tumor, and measured microRNA levels in the two
types of tissue.
Patients who fared worst had the lowest levels of two particular
microRNAs─miR-205 and let-7d─in their tumor tissue. Specifically,
these patients were four times more likely to have an earlier metastasis
or local-regional recurrence of their cancer than patients with higher
levels of miR-205 and let-7d in tumor tissue.
These findings may eventually be put to practical use, allowing physicians
to identify potentially aggressive head and neck cancers and choose the
most appropriate treatment. "A biologic marker identifying aggressive
tumors would allow us to direct therapy more appropriately, minimizing
over or under-treatment," explained Richard Smith, M.D., the lead
clinician on the paper. Dr. Smith is associate professor of clinical
otorhinolaryngology-head & neck surgery and associate professor of
surgery at Einstein, and vice-chair of otorhinolaryngology-head & neck
surgery at Einstein and Montefiore.
"In addition, these molecules, or modified forms of these molecules, can
potentially be used in treatment because their small size allows them to
be reintroduced into cells with the possibility of altering the behavior
of a tumor," says Geoffrey Childs, Ph.D., professor of pathology at
Einstein and corresponding author of the article.
"Our next steps are to confirm these results in a new patient population
and to find additional markers that would allow us to develop a
reproducible and accurate prognostic test," explained Nicolas Schlecht,
Ph.D., assistant professor of epidemiology and population health, and of
medicine at Einstein. Dr. Schlecht is also the Miriam Mandel faculty
scholar in cancer research and a senior author of the paper.
###
121
Other Einstein and Montefiore faculty members involved in this study were
Melissa Fazzari, Margaret Brandwein-Gensler, Quan Chen, Robert Burk,
Michael Prystowsky and Thomas Belbin.
The paper titled "Low-Level Expression of MicroRNAs let-7d and miR-205
are Prognostic Markers of Head and Neck Squamos Cell Carcinoma" appeared
in the March 2009 issue of the American Journal of Pathology and can be
found at: http://ajp.amjpathol.org/
About Albert Einstein College of Medicine of Yeshiva University
Albert Einstein College of Medicine of Yeshiva University is one of the
nation's premier centers for research, medical education and clinical
investigation. It is the home to some 2,000 faculty members, 750 M.D.
students, 350 Ph.D. students (including 125 in combined M.D./Ph.D.
programs) and 380 postdoctoral investigators. Last year, Einstein
received more than $130 million in support from the NIH. This includes
the funding of major research centers at Einstein in diabetes, cancer,
liver disease, and AIDS. Other areas where the College of Medicine is
concentrating its efforts include developmental brain research,
neuroscience, cardiac disease, and initiatives to reduce and eliminate
ethnic and racial health disparities. Through its extensive affiliation
network involving five hospital centers in the Bronx, Manhattan and Long
Island – which includes Montefiore Medical Center, The University
Hospital and Academic Medical Center for Einstein – the College runs one
of the largest post-graduate medical training program in the United States,
offering approximately 150 residency programs to more than 2,500
physicians in training. For more information, please visit
www.aecom.yu.edu.
3 月 18 日
Semafore Achieves A Preclinical Milestone With SF2626,
A PI3K-MEK Dual Pathway Kinase Inhibitor
Semafore Pharmaceuticals, Inc. announced that it has achieved proof of concept in its CRIMP
(Control Resulting from Inhibiting Multiple Pathways) kinase platform by designing a small
molecule
that
was
demonstrated
to
inhibit
members
of
both
the
PI3K
(Phosphoinositide-3-kinase) pathway and the Ras-MAPK (Ras-mitogen activated protein
kinase) pathway. Specifically, SF2626 has demonstrated the ability to inhibit both PI3K and
MEK, the key component of the RAS/RAF/MEK/ERK pathway. Both PI3K and MEK are
frequently activated in human tumors and are thus considered high value targets in treating
cancer. SF2626 is the first combination PI3K and MEK kinase inhibitor that, in preclinical
122
studies, blocks both pathways simultaneously.
There is clear rationale for inhibiting both pathways in treating cancer. Both the PI3K pathway
and the Ras-MAPK pathways have emerged as central conduits of cell signaling networks that
regulate cell growth and survival. Recent scientific studies demonstrate that the Ras-MAPK
pathway has the ability to cross-talk to the PI3K pathway thereby activating it and that in some
cancers both pathways require inhibition to induce programmed cell death.
Additionally, clinical studies in cancer patients with KRAS mutations show that EGFR inhibitors
alone are not sufficient to block the downstream activation of the Ras-MAPK pathway. In these
patients, it may also be necessary to block both pathways to inhibit cancer cell growth.
With the evolving knowledge of cancer biology and further understanding of the mechanisms
of drug resistance Semafore's CRIMP platform technology offers a distinctive approach to
rational drug design for combination pathway kinase inhibitors.
Semafore's dual PI3K-MEK kinase inhibitor, SF2626, is a promising lead for targeting cancer.
The Company is actively seeking a partner for the continued development of SF2626 and
other pipeline inhibitors.
About Semafore
Semafore is a clinical stage drug discovery and development company focused on small
molecule modulators of the PI3 kinase and PTEN cell signaling pathway, a promising target
pathway for multiple disorders, including the company's focus - cancer. Semafore is a leader in
the development of PI3K inhibitors and one of the first biopharmaceutical companies to focus
on both PI3K and PTEN. The Company has successfully discovered and is developing a
portfolio of drug candidates addressing these targets. Semafore is also leveraging its
experience in the PI3K arena to identify and design inhibitors that block multiple pathways.
3 月 19 日
Researchers Identify Genetic Markers For Aggressive
Head And Neck Cancer
Scientists at Albert Einstein College of Medicine of Yeshiva University have identified genetic
markers that signal poor outcomes for patients with head and neck cancer. These findings
could one day lead to a genetic test that could help select or predict successful treatment
options for patients with this type of cancer. The results were published in the American
Journal of Pathology.
Head and neck cancer refers to tumors in the mouth, throat or larynx (voice box). Each year,
about 40,000 men and women in the U.S. develop head and neck cancer, making it the sixth
most common cancer in the U.S. Surgery, chemotherapy and/or radiation are the main
123
treatment options but cause serious side effects: surgery may involve removing large areas of
the tongue, throat, or neck and can affect appearance, and any type of therapy can cause
swallowing or speech problems that can significantly affect quality of life. Despite curative
treatment attempts, on average only about half of patients survive beyond five years after
treatment. This is greatly affected by the size and location of the tumor.
The Einstein study focuses on microRNAs, a recently identified class of short RNA molecules
that play key roles in regulating gene expression. Abnormal microRNA levels have been
associated with all types of cancer yet examined.
In previous research, the Einstein scientists and other groups reported that approximately 50
specific microRNAs were expressed at higher or lower levels in head and neck tumor cell lines
compared with normal cells. In this study, the Einstein researchers, for the first time, have
linked levels of specific microRNAs with tumor recurrence and poorer survival in head and
neck cancer.
The Einstein team analyzed samples from 104 head and neck cancer patients from Montefiore
Medical Center, The University Hospital and Academic Medical Center for Einstein. The
patients were treated and followed over five years. At the time of cancer diagnosis and before
any therapy, researchers removed samples tumor tissue from patients, as well as normal
tissue adjacent to their tumor, and measured microRNA levels in the two types of tissue.
Patients who fared worst had the lowest levels of two particular microRNAs miR-205 and
let-7d in their tumor tissue. Specifically, these patients were four times more likely to have an
earlier metastasis or local-regional recurrence of their cancer than patients with higher levels
of miR-205 and let-7d in tumor tissue.
These findings may eventually be put to practical use, allowing physicians to identify
potentially aggressive head and neck cancers and choose the most appropriate treatment. "A
biologic marker identifying aggressive tumors would allow us to direct therapy more
appropriately, minimizing over or under-treatment," explained Richard Smith, M.D., the lead
clinician on the paper. Dr. Smith is associate professor of clinical otorhinolaryngology-head &
neck surgery and associate professor of surgery at Einstein, and vice-chair of
otorhinolaryngology-head & neck surgery at Einstein and Montefiore.
"In addition, these molecules, or modified forms of these molecules, can potentially be used in
treatment because their small size allows them to be reintroduced into cells with the possibility
of altering the behavior of a tumor," says Geoffrey Childs, Ph.D., professor of pathology at
Einstein and corresponding author of the article.
"Our next steps are to confirm these results in a new patient population and to find additional
markers that would allow us to develop a reproducible and accurate prognostic test," explained
Nicolas Schlecht, Ph.D., assistant professor of epidemiology and population health, and of
medicine at Einstein. Dr. Schlecht is also the Miriam Mandel faculty scholar in cancer research
124
and a senior author of the paper.
Other Einstein and Montefiore faculty members involved in this study were Melissa Fazzari,
Margaret Brandwein-Gensler, Quan Chen, Robert Burk, Michael Prystowsky and Thomas
Belbin.
The paper titled "Low-Level Expression of MicroRNAs let-7d and miR-205 are Prognostic
Markers of Head and Neck Squamos Cell Carcinoma" appeared in the March 2009 issue of
the American Journal of Pathology and can be found at: http://ajp.amjpathol.org
About Albert Einstein College of Medicine of Yeshiva University
Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers
for research, medical education and clinical investigation. It is the home to some 2,000 faculty
members, 750 M.D. students, 350 Ph.D. students (including 125 in combined M.D./Ph.D.
programs) and 380 postdoctoral investigators. Last year, Einstein received more than $130
million in support from the NIH. This includes the funding of major research centers at Einstein
in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is
concentrating its efforts include developmental brain research, neuroscience, cardiac disease,
and initiatives to reduce and eliminate ethnic and racial health disparities. Through its
extensive affiliation network involving five hospital centers in the Bronx, Manhattan and Long
Island which includes Montefiore Medical Center, The University Hospital and Academic
Medical Center for Einstein the College runs one of the largest post-graduate medical training
program in the United States, offering approximately 150 residency programs to more than
2,500 physicians in training. For more information, please visit http://www.aecom.yu.edu.
Albert Einstein College of Medicine of Yeshiva University
1300 Morris Park Ave.
Bronx
NY 10461
United States
3 月 19 日
Herceptin Now Shown To Significantly Prolong The
Lives
Of
Patients
With
HER2-positive
Advanced
Stomach Cancer
Roche announced results from a major international study which show that adding Herceptin
(trastuzumab) to standard chemotherapy significantly prolongs lives of patients with
HER2-positive stomach (gastric) cancer. The results are from ToGA, a large international
Phase III trial investigating the benefit of Herceptin as the first therapy for patients with
advanced and inoperable stomach cancer (first line). Full data will be presented at an
125
upcoming medical meeting.i
"Stomach cancer is often incredibly hard to treat, as it is frequently diagnosed at a late stage"
said principal investigator Prof. Eric Van Cutsem, University Hospital Gasthuisberg in Leuven,
Belgium. "Based on the clear positive outcome from this clinical study, the addition of
Herceptin to chemotherapy offers a new important option for patients with HER2-positive
stomach cancer as Herceptin extends survival and will bring this group of patients a significant
benefit."
Stomach cancer is the second most common cause of cancer-related death in the world with
over 900,000 new cases diagnosed each year. Early diagnosis is difficult because most
patients do not show symptoms in the early stage. Advanced stomach cancer is associated
with a poor prognosis, the average time patients survive after diagnosis is approximately 10
months with currently available therapies.ii Approximately 22% of stomach tumours
overexpress HER2.iii
"Herceptin was a breakthrough treatment for patients with HER2-positive breast cancer and
has become the foundation of care across all stages of HER2-positive breast cancer", said
William M. Burns, CEO of Roche's Pharmaceuticals Division. "The ToGA study shows for the
first time that Herceptin extends the lives of patients in a cancer other than breast cancer.
Advanced stomach cancer is a devastating disease for which there are currently few treatment
options. Consequently, the targeted therapy Herceptin will become an integral part of
treatment for this type of cancer."
About the ToGA study
ToGA is the first randomised Phase III trial investigating the use of Herceptin in patients with
inoperable locally advanced, recurrent and/or metastatic HER2-positive gastric cancer.
Approximately 3,800 patients were tested for HER2-positive tumours and 594 patients with
HER2-positive disease were enrolled into the study. The rationale for conducting this trial was
based on the knowledge that the targeted therapy Herceptin has demonstrated unprecedented
efficacy in the treatment of HER2-positive breast cancer. In addition, the overexpression of
HER2 was also observed in stomach cancer. A targeted anti-cancer therapy is a type of
medication that blocks the growth of cancer cells by interfering with specific molecules which
cause a tumor to grow.
In the ToGA study, patients were randomised to receive one of the following regimens
as their first line of treatment:
-- A fluoropyrimidine (Xeloda or 5-FU) and cisplatin every 3 weeks for 6 cycles
-- Herceptin 6mg/kg every 3 weeks until progression in combination with a fluoropyrimidine
and cisplatin for 6 cycles
126
The primary objective of the study was to demonstrate superiority in overall survival of the
Herceptin-containing treatment arm compared to the chemotherapy alone arm. The
pre-planned interim analysis was triggered by the occurrence of 347 events. Secondary
endpoints for the study included progression-free survival, overall response rate, duration of
response, safety and quality of life. In the ToGA study, no new or unexpected side effects were
observed.
About Herceptin (trastuzumab)
Herceptin is a humanised antibody, designed to target and block the function of HER2, a
protein produced by a specific gene with cancer-causing potential. The mode of action of
Herceptin is unique in that it activates the body's immune system and suppresses HER2 to
target and destroy the tumour. Herceptin has demonstrated unprecedented efficacy in treating
both early and advanced (metastatic) HER2-positive breast cancer. Given on its own as
monotherapy as well as in combination with or following standard chemotherapy, Herceptin
has been shown to improve response rates, disease-free survival and overall survival while
maintaining quality of life in women with HER2-positive breast cancer.
Herceptin received approval for use in the European Union for advanced (metastatic)
HER2-positive breast cancer in 2000, and for early HER2-positive breast cancer in 2006. In
the advanced setting, Herceptin is now approved for use as a first-line therapy in combination
with paclitaxel where anthracyclines are unsuitable, as first-line therapy in combination with
docetaxel, and as a single agent in third-line therapy. It is also approved for use in combination
with an aromatase inhibitor for the treatment of post-menopausal patients with HER2 and
hormone receptor co-positive metastatic breast cancer. In the early setting, Herceptin is
approved for use following standard (adjuvant) chemotherapy.
Herceptin is currently being evaluated for treatment of HER2-positive stomach cancer through
an extensive international clinical trial programme.
Herceptin is marketed in the United States by Genentech, in Japan by Chugai and
internationally by Roche. Since 1998, Herceptin has been used to treat nearly 600,000
patients with HER2-positive breast cancer worldwide.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world's leading research-focused
healthcare groups in the fields of pharmaceuticals and diagnostics. As the world's biggest
biotech company and an innovator of products and services for the early detection, prevention,
diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to
improving people's health and quality of life. Roche is the world leader in in-vitro diagnostics
and drugs for cancer and transplantation, and is a market leader in virology. It is also active in
other major therapeutic areas such as autoimmune diseases, inflammatory and metabolic
disorders and diseases of the central nervous system. In 2008 sales by the Pharmaceuticals
127
Division totalled 36.0 billion Swiss francs, and the Diagnostics Division posted sales of 9.7
billion francs. Roche has R&D agreements and strategic alliances with numerous partners,
including majority ownership interests in Genentech and Chugai, and invested nearly 9 billion
Swiss francs in R&D in 2008. Worldwide, the Group employs about 80,000 people. Additional
information is available on the Internet at http://www.roche.com.
References
i) TBC ASCO 2009
ii) Ohtsu A. J Gastroenterol 2008;43:256-264
iii) Bang YJ et al. ASCO 2008 (poster no. 4526)
Roche
3 月 19 日
Lab-On-A-Chip Homes In On How Cancer Cells Break
Free
Johns Hopkins engineers have invented a method that could be used to help figure out how
cancer cells break free from neighboring tissue, an "escape" that can spread the disease to
other parts of the body. The new lab-on-a-chip, described in the March issue of the journal
Nature Methods, could lead to better cancer therapies.
"Studying cell detachment at the subcellular level is critical to understanding the way cancer
cells metastasize," says principal investigator Peter Searson, Reynolds Professor of Materials
Science and Engineering. "Development of scientific methods to study cell detachment may
guide us to prevent, limit or slow down the deadly spreading of cancer cells."
His team's research focuses on a missing puzzle piece in the common but unfortunate events
that can occur in cancer patients. For example, cancer that starts in the breast sometimes
spreads to the lungs.
That's because tumor cells detach and travel through the bloodstream to settle in other tissues.
Scientists have learned much about how cancer cells attach to these surfaces, but they know
little about how these insidious cells detach because no one had created a simple way to study
the process.
Searson and two other scientists from Johns Hopkins' Whiting School of Engineering have
solved this problem with a lab-on-a-chip device that can help researchers study cell
detachment. With this device, they hope to discover exactly how cancer cells spread.
The lab-on-a-chip device consists of an array of gold lines on a glass slide. Molecules
promoting the formation of cell attachments are tethered to the gold lines like balloons tied to
string. A cell is placed on the chip, atop these molecules. The cell spreads across several of
128
the gold lines, forming attachments to the surface of the chip with help from the molecules.
Then, the tethered molecules are released from one of the lines by a chemical reaction,
specifically by "electrochemical reduction," Searson explains. Where these molecules are
detached, that portion of the cell loses its grip on the surface of the chip. This segment of the
cell pauses for a moment and then contracts forcefully toward its other end, which is still
attached to the chip. The researchers were able to film this "tail snap" under a microscope.
"It's very dramatic," says Denis Wirtz, a Johns Hopkins professor of chemical and biomolecular
engineering and co-author of the Nature Methods paper. "The cell stretches way, way out
across the chip and then, on command, the tail snaps toward the body of the cell."
Cells survive this programmed-release process and can be tested again and again, the
researchers said.
Bridget Wildt, a materials science and engineering doctoral student in Searson's lab, used the
device to perform and record movies of the live-cell experiments. Wildt tested cells from the
connective tissue of mice during these experiments, but the team plans to try other types of
cells in the future.
"In the movies, you can see that the cell doesn't move immediately after the chemical reaction
is triggered. We refer to this phenomenon as the induction time of the cell," Wildt says. "After
this induction time, the cell then snaps back and contracts. We analyze the rate of the cell's
contraction and then compare this information to separate cells released under different
conditions using chemicals called inhibitors. From these results we are beginning to
understand the processes that regulate cell detachment at the molecular level."
The researchers have speculated that the induction time for cancer cells, as compared to
noncancerous cells, would be shorter because cancer cells are more pliable. In the near future,
Wildt says, they plan to test this hypothesis in experiments with cancer cells. If this assumption
proves correct, it may give them a tool to differentiate between cancerous and noncancerous
cells.
Notes:
Searson is director and Wirtz is associate director of the Johns Hopkins Institute for
NanoBioTechnology. Their work was supported by grants from the U.S. National Institutes of
Health, National Science Foundation and the Howard Hughes Medical Institute. Wildt's
participation in the research was funded by the Achievement Rewards for College Scientists
Foundation.
The new study - "Programmed subcellular release for studying the dynamics of cell
detachment," Bridget Wildt, Denis Wirtz, and Peter C. Searson - can be viewed online at:
http://www.nature.com/nmeth/journal/v6/n3/full/ nmeth.1299.html.
129
Source: Mary Spiro
3 月 19 日
Biological Clue In Brain Tumour Development
Scientists at The University of Nottingham have uncovered a vital new biological clue that
could lead to more effective treatments for a children's brain tumour that currently kills more
than 60 per cent of young sufferers.
Clinician-scientists at the University's Children's Brain Tumour Research Centre, working on
behalf of the Children's Cancer and Leukaemia Group (CCLG), have studied the role of the
WNT biological pathway in central nervous system primitive neuroectodermal tumours (CNS
PNET), a type of brain tumour that predominantly occurs in children and presently has a very
poor prognosis.
In a paper published in the British Journal of Cancer, they have shown that in over one-third of
cases, the pathway is 'activated', suggesting that it plays a role in tumour development. The
research also highlighted a link between WNT pathway activation and patient survival patients who had a CNS PNET tumour that was activated survived for longer than those
without pathway activation.
The reason for the link between WNT pathway activation and better patient prognosis is as yet
unclear. It could be that these tumours represent a less aggressive subset or that pathway
activation itself actually harms the tumour. However, the pathway could represent an important
new target for the treatment of more effective drugs, with fewer side effects.
Senior author Professor Richard Grundy, from the Children's Brain Tumour Research Centre,
said: "The principal aim of our research is to reduce the morbidity and mortality of children with
central nervous system tumours through improved understanding of tumour biology. Following
on from this, we need to translate this knowledge into effective new treatments for brain
tumours through the development and assessment of accurately targeted treatments that will
cause fewer side effects than conventional chemotherapy or radiotherapy and be more
effective. The ultimate aim is to develop 'drugs' that target just the abnormal genes in cancer
cells, rather than the current norm which involves the indiscriminate destruction of dividing
cells which might be healthy or malignant. Overall, this is an important finding in a poorly
understood, poor prognosis disease, which we hope, in time, will lead to the development of
new treatments for CNS PNETs.
"We hope our findings will lead to a more detailed understanding of CNS PNETS, which is
crucial if we are to ensure each child receives the most appropriate treatment for their disease
and that we reduce the number of children in which their cancer recurs."
In total, around 450 children and young adults under 18 years are diagnosed with a brain
tumour each year in the UK. Overall, 60 per cent of children with the cancer in the UK can be
130
successfully treated, but survival for CNS PNETs is less than 40 per cent.
Notes:
Funding was provided by the Connie and Albert Taylor Trust, The Samantha Dickson Brain
Tumour Trust, the Brain Tumour Research Fund Birmingham Children's Hospital Special
Trustees.
The paper, An Investigation of WNT Pathway Activation and Association with Survival in
Central Nervous System Primitive Neuroectodermal Tumours (CNS PNET) by HA Rogers, S
Miller, J Lowe, M-A Brundler, B Coyle and RG Grundy is published in the latest edition of the
British Journal of Cancer.
About the Children's Cancer and Leukaemia Group
Cancer Research UK is the major funding provider of the Children's Cancer and Leukaemia
Group and funds the UK clinical trials work of the group in 21 paediatric centres throughout the
British Isles. The Children's Cancer and Leukaemia Group is the national professional body
responsible for the organisation, treatment and management of virtually all children with
cancer in the UK. The group is acknowledged as one of the world's leading childhood cancer
clinical trial groups who have made a significant contribution to the international success in
treating childhood cancer, resulting in improvements in survival.
British Journal of Cancer
The BJC is owned by Cancer Research UK. Its mission is to encourage communication of the
very best cancer research from laboratories and clinics in all countries. Broad coverage, its
editorial independence and consistent high standards have made BJC one of the world's
premier general cancer journals. http://www.bjcancer.com.
The University of Nottingham
The University of Nottingham is ranked in the UK's Top 10 and the World's Top 100 universities
by the Shanghai Jiao Tong (SJTU) and Times Higher (THE) World University Rankings.
More than 90 per cent of research at The University of Nottingham is of international quality,
according to RAE 2008, with almost 60 per cent of all research defined as 'world-leading' or
'internationally excellent'. Research Fortnight analysis of RAE 2008 ranks the University 7th in
the UK by research power. In 27 subject areas, the University features in the UK Top Ten, with
14 of those in the Top Five.
The University provides innovative and top quality teaching, undertakes world-changing
research, and attracts talented staff and students from 150 nations. Described by The Times
as Britain's 'only truly global university', it has invested continuously in award-winning
131
campuses in the United Kingdom, China and Malaysia. Twice since 2003 its research and
teaching academics have won Nobel Prizes. The University has won the Queen's Award for
Enterprise in both 2006 (International Trade) and 2007 (Innovation - School of Pharmacy), and
was named 'Entrepreneurial University of the Year' at the Times Higher Education Awards
2008.
Nottingham was designated as a Science City in 2005 in recognition of its rich scientific
heritage, industrial base and role as a leading research centre. Nottingham has since
embarked on a wide range of business, property, knowledge transfer and educational
initiatives (http://www.science-city.co.uk) in order to build on its growing reputation as an
international centre of scientific excellence. The University of Nottingham is a partner in
Nottingham: the Science City.
Source: Emma Thorne
University of Nottingham
3 月 19 日
Austrian Scientists Identify A Potential Tumor
Suppressor
The gene Myc is an important factor for the growth of organisms by cell division. It causes the
production of a protein which, as a transcription factor, controls the expression of up to 15 % of
all human genes. When this gene mutates to an oncogene, the cell proliferates excessively
and apoptosis is inhibited. Thereby the gene plays a decisive role in the development of many
tumors. The problem is that pharmacological substances do not target Myc as it does not have
enzymatic activity of its own. Thus, scientists worldwide are trying to find alternative ways to
inhibit this oncogene.
A team of scientists led by Klaus Bister and Markus Hartl of the Institute of Biochemistry and
the Centre for Molecular Biosciences of the University of Innsbruck may have made an
important step towards achieving this goal.
Suppressing pathological cell growth
For the first time, the scientists have shown that Myc suppresses the expression of the gene
BASP1. This evidence prompted them to test the effect of BASP1 on the oncogene. In cell
experiments they proved that BASP1 specifically inhibits the uncontrolled proliferation of Myc.
"Until now the precise biochemical function of BASP1 was unknown", Professor Bister
explains. "However, in our experiments we have found clear evidence that Myc-induced cell
transformation can be specifically inhibited by BASP1, and consequently, the gene functions
as a tumor suppressor." This finding may facilitate the development of new drugs which keep
the development of tumors under control.
132
Notes:
This release is available in German.
The team of Bister published the findings in the online edition of the American journal
Proceedings of the National Academy of Sciences (PNAS). The scientists are supported by
the Austrian Science Fund.
Source: Professor Klaus Bister
University of Innsbruck
3 月 19 日
Obese People Seem To Fare Worse After Pancreatic
Cancer Surgery
After having surgery for pancreatic cancer, obese people with a BMI of 35 or more seem to be
the most likely to have poorer outcomes such as cancer that has spread to the lymph nodes,
lower rates of survival and higher rates of cancer recurrence.
The study was the work of Dr Jason B Fleming, from the University of Texas MD Anderson
Cancer Center in Houston, and colleagues and is published online in the March issue of the
Archives of Surgery a Journal of the American Medical Association.
A person is classed as obese if their Body Mass Index (BMI, weight in kilos divided by the
square of height in metres, kg/m2) is 30 or more. The "ideal" or normal range is 18.5 to 25:
being outside of this range is linked to various health problems for underweight, overweight
and obese people.
Rates of obesity have risen sharply in the US in the last 20 years, wrote the authors in their
background information.
"In many obesity-related diseases and malignant neoplasms [cancerous tumors], an increased
prevalence of pancreatic cancer has been reported in numerous epidemiologic and cohort
studies focusing on obese patients," they wrote.
"Further, obesity has been associated with decreased survival in patients with pancreatic
adenocarcinoma, although the mechanism remains unknown," they added.
For this study they wanted to examine the link between obesity, as measured by BMI, and
medical outcomes and survival of patients who have had their pancreas removed to treat
pancreatic adenocarcinoma.
The study looked at the results retrospectively (that is they found data relating to surgeries that
133
had already taken place as opposed to setting up the study beforehand). The researchers
looked at records from 285 consecutive patients whose BMI data was available and who had
undergone "potentially curative pancreas resection to treat adenocarcinoma".
All the patients had attended a referral center with a dedicated multidisciplinary pancreas
cancer program between 1 January 1999 and 31 October 2006.
In their statistical analysis the researchers looked for links between BMI and other prognostic
information and the incidence of lymph nodes metastasis (how far the cancer had spread if it
had), and survival rates.
The results showed that:

Over the 16 month midpoint of the study (median follow up), 152 patients died (53 per
cent).

Patients whose BMI was over 35 survived a median of 13.2 months compared with
27.4 months for those whose BMI was under 23.

At the last follow up, 15 of 20 patients (75 per cent) whose BMI was over 35 had died,
compared with 137 of 265 patients (52 per cent) whose BMI was 35 or less.

Cancer spreading to the lymph nodes was 12 times more likely in obese patients with
BMI over 35 than in patients whose BMI was 35 and under.

Disease-free and overall survival was also lower in patients whose BMI was above 35,
and the risk of cancer recurrence and death after having their pancreas removed was
nearly twice that of patients whose BMI was 35 and under.
The researchers concluded that:
"Obese patients with a BMI of more than 35 are more likely to have node-positive pancreatic
cancer and decreased survival after surgical resection."
"Data suggest that the negative influence of BMI of more than 35 on cancer-related end points
is unrelated to the potential complexity of performing major oncologic surgery in obese
patients," they added.
Other studies have shown links between BMI over 35 and increased risk of death from
pancreatic cancer, noted the authors, who wrote that:
"Our findings extend these observations to those patients who undergo surgery to treat
pancreatic cancer and suggest that obesity is a host factor affecting tumor biology independent
of the difficulties (patient- and treatment-related) involved in delivering oncologic care in obese
patients."
"Future investigations should include a search for systemic or tumor biomarkers in this group
of patients that could provide additional insight," they added.
134
"Influence of Obesity on Cancer-Related Outcomes After Pancreatectomy to Treat
Pancreatic Adenocarcinoma."
Jason B. Fleming; Ricardo J. Gonzalez; Maria Q. B. Petzel; E. Lin; Jeffrey S. Morris; Henry
Gomez; Jeffrey E. Lee; Christopher H. Crane; Peter W. T. Pisters; Douglas B. Evans.
Archives of Surgery 2009;144(3):216-221.
Vol. 144 No. 3, March 2009
3 月 19 日
European Association Of Urology Launches New Clinical
Guidelines For 2009 -- Kidney Cancer
A number of updated guidelines will be presented at the 24th Annual Congress of the
European Association of Urology (EAU) held in Stockholm, from 17 though 21 March. The
abridged versions - Pocket Guidelines - which are based on the extended text documents will
also be available in Stockholm to all EAU members and press.
Production of clinical guidelines is one of the core activities of the organisation. Close to 150
experts split up over 18 different topic-oriented panels, are involved in this ongoing process.
Guidelines aim to present the best evidence available on a given pathology and provide a
standardized approach to the treatment of urological conditions. Ultimately, healthcare
professionals must make their own decisions about care on a case-by-case basis, after
consultation with their patients, using their clinical judgment, knowledge and expertise.
Kidney Cancer
Due to the enhanced use of imaging techniques over the past years a stage shift has been
seen in the field of renal cell cancer with a volume increase in the incidental detection of
smaller cancers (< 4 cm). Thirty percent of these findings are benign. The treatment of
metastatic small tumours show a decrease in death rates. A considerable portion of these
tumours can be treated with nephron sparing surgery. Additionally, a number of targeted
agents have become available with several more expected shortly.
The panel updated these Kidney Cancer guidelines since for several targeted agents more
mature data have been published and validated prognostic nomograms predicting treatment
outcome accuracy are available for more treatment options.
The panel do not recommend Interferon-alpha (IFN-alpha) in a first-line setting as
monotherapy in the treatment of metastatic RCC. Sunitinib and Bevacizumab + IFN-alpha are
recommended as first-line therapy in low- and intermediate-risk patients while
Temsirolimus is recommended for high risk patients; Sorafenib and Everolimus can be
recommended as second-line therapy after cytokine and tyrosine kinase inhibitor (TKI) failure,
respectively.
135
The expectation is that further targeted agents will be on the market shortly. Also the role of
molecular medicine in the treatment of renal cell carcinoma will become more prominent. A
subsequent update will take this information in, once sufficiently data is available.
The panel consists of an expert group chaired by B. Ljungberg and includes D.C. Hanbury,
M.A. Kuczyk, A.S. Merseburger, P.F.A. Mulders, J-J. Patard and I.C. Sinescu.
Source: Lindy Brouwer
European Association of Urology
3 月 19 日
MicroRNA Undermines Tumor Suppression
FINDINGS: Scientists at the Whitehead Institute for Biomedical Research and the National
University of Singapore have discovered the first microRNA (miRNA) capable of directly
tamping down the activity of the well known tumor-suppressor gene, p53, While p53 functions
to prevent tumor formation, the p53 gene is thought to malfunction in more than 50% of
cancerous tumors.
RELEVANCE: The study reports the first time a miRNA has been shown to directly affect the
p53 protein level, although researchers have previously identified other genes and miRNAs
that indirectly affect p53's activity.
A small piece of RNA, or microRNA (miRNA), ratchets down the activity of the
tumor-suppressor gene p53, according to a study by Whitehead Institute and National
University of Singapore researchers.
While p53 functions to suppress tumor formation, the p53 gene is thought to malfunction in
more than 50% of cancerous tumors.
The study published online March 17 in Genes and Development reports the first time that a
miRNA has been shown to directly affect the p53 gene, although researchers have previously
identified other genes and miRNAs that regulate p53's activity indirectly.
"For critical genes like p53, it's important that they are maintained at the right level in the cell,"
says Beiyan Zhou, a postdoctoral researcher in the lab of Whitehead Member Harvey Lodish
and mentor to the paper's first author, Minh Le. "Le's work describes one more layer of
regulatory mechanism that balances p53 gene expression."
miRNAs, short snippets of RNA, usually reduce how often a certain gene is translated into a
protein. When a miRNA matches with and binds to a given messenger RNA coding for a
specific protein, thereby preventing that messenger RNA from acting as a template for protein
creation.
To investigate whether any miRNAs directly affect p53, Le, who is a joint graduate student in
136
Lodish's lab and in the lab of Bing Lim at the National University of Singapore, searched the
p53 gene for any sites that matched with known miRNAs from two databases. Only
miRNA125b potentially has p53 target sites in humans, in zebrafish, and in many other
vertebrates, indicating that it was important enough in cellular processes to be conserved
through evolution.
Le tested miRNA125b's effects on several types of cells known to express p53, including
human neural and lung cells. When Le reduced the amount of miRNA125b in the cells, p53
levels and the number of cells undergoing apoptosis (a type of programmed cell death that can
be triggered by p53) both increased, whereas an increase in miRNA125b levels decreased
levels of p53 and the number of apoptotic cells.
To confirm that miRNA125b played a similar role in developing organisms, Le changed the
miRNA125b levels in zebrafish embryos. When she reduced miRNA125b levels in the
embryos, cellular p53 levels and apoptosis both increased.
"Taking all of this data together, the p53 pathway is a major target of miRNA125b," says
Lodish, who is also a professor of biology and bioengineering at MIT. "Most miRNAs have
multiple targets, but there are a few cases that a miRNA has one major target and this is one
of them."
Notes:
This research was funded by the National Institutes of Health and the Singapore-MIT Alliance.
Written by Nicole Giese.
Harvey Lodish's primary affiliation is with Whitehead Institute for Biomedical Research, where
his laboratory is located and all his research is conducted. He is also a professor of biology
and a professor of bioengineering at Massachusetts Institute of Technology.
Full Citation: "MicroRNA-125b is a novel negative regulator of p53"
Genes & Development, online March 18, 2009
Minh T. N. Le (1,2), Cathleen The (3,7), Ng Shyh-Chang (2,7), Huangming Xie (1,2,4), Beiyan
Zhou (4), Vladimir Korzh (3), Harvey F. Lodish (1,4,5), Bing Lim (1,2,6).
1. Computation and Systems Biology, Singapore-MIT
Alliance, 4 Engineering Drive 3, Singapore 117576
2. Stem Cell and Developmental Biology, Genome
Institute of Singapore, 60 Biopolis Street, Genome,
Singapore 138672
137
3. Fish Developmental Biology, Institute of Molecular and
Cell Biology, 61 Biopolis Drive, Proteos, Singapore
138673
4. Whitehead Institute for Biomedical Research, 9
Cambridge Center, Suite 601, Cambridge, MA 02142,
USA
5. Department of Biology, Massachusetts Institute of
Technology, Cambridge, MA 02142, USA
6. CLS 442 Beth Israel Deaconess Medical Center,
Harvard Medical School, 300 Brookline Ave, Boston,
MA 02215, USA
7. These authors contributed equally to this paper as
co-second authors.
Source: Nicole Giese
Whitehead Institute for Biomedical Research
3 月 19 日
New Generation Oral Vaccine Uses Dairy Probiotics To
Protect Against Disease
Instead of a dreaded injection with a needle, someday getting vaccinated against disease may
be as pleasant as drinking a yogurt smoothie.
A researcher from the Northwestern University Feinberg School of Medicine has developed a
new oral vaccine using probiotics, the healthy bacteria that are found in dairy products like
yogurt and cheese. He has successfully used the approach in a preclinical study to create
immunity to anthrax exposure. He also is using the method to develop a breast cancer vaccine
and vaccines for various infectious diseases.
This new generation vaccine has big benefits beyond eliminating the "Ouch!" factor. Delivering
the vaccine to the gut -- rather than injecting it into a muscle -- harnesses the full power of the
body's primary immune force, which is located in the small intestine.
"This is potentially a great advance in the way we give vaccines to people," said Mansour
Mohamadzadeh, the lead author and an associate professor of medicine in gastroenterology
at the Feinberg School.
"You swallow the vaccine, and the bacteria colonize your intestine and start to produce the
vaccine in your gut," Mohamadzadeh said. "Then it's quickly dispatched throughout your body.
138
If you can activate the immune system in your gut, you get a much more powerful immune
response than by injecting it. The pathogenic bacteria will be eliminated faster."
Most vaccines consist of protein and won't maintain their effectiveness after being digested by
the stomach. However, the lactobacillus protects the vacThe Northwestern study was reported
in a recent issue of the Proceedings of the National Academy of Science.
There are other advantages to the new oral vaccine. Probiotics, which are natural immune
stimulators, eliminate the need for a chemical in traditional vaccines that inflames the immune
system and triggers a local immune response. The chemical, called an adjuant, may cause
side effects such as dizziness, arm swelling and vomiting. Probiotic vaccines also are
inexpensive to produce.
The specially engineered vaccine gives more immune bang for the buck than an injected one
because it induces a local and a systemic immune response. The vaccine targets the first line
of gut immune cells called dendritic cells -- the commanders-in-chiefs of the immune system.
They engulf the vaccine then instruct the immune system's foot soldiers -- killer T-cells and
B-cells -- to seek out and destroy any cells in the body infected with a particular bacterium or
virus.
In the study, Mohamadzadeh fed mice the new oral anthrax vaccine, and then exposed them
to anthrax bacteria. Eighty percent of the mice survived, which is comparable to the results
when mice were injected with anthrax vaccine, he said.
"Their immune response was higher and more robust than with the injected vaccine,"
Mohamadzadeh said. The mice generated a much higher T and B immunity against the
pathogenic bacteria.
Mohamadzadeh's vaccine technology can be applied to many other diseases. He is
developing an oral vaccine for breast cancer using probiotics. The vaccine would use the
Her2/neu breast cancer antigen, a protein highly produced by breast tumor cells, and train the
immune system to destroy any cells producing Her2/neu, he said.
In addition, Mohamadzadeh has developed a "multi-tasking" cancer vaccine against breast,
colon and pancreatic cancer that soon will be tested in mouse models.
The technology also can be used to develop a probiotic vaccine for HIV, hepatitis C and the flu,
he said.
Terrence Barrrett, M.D., chief and professor of gastroenterology at the Feinberg School, said
delivering a vaccine to the gut is the most logical route.
"Nature isn't used to seeing antigens injected into a muscle," said Barrett, who also is a
physician at Northwestern Memorial Hospital. "The place where your immune system is
139
designed to encounter and mount a defense against antigens is your gut."
Notes:
The study was funded by the National Institutes of Health and the North Carolina Dairy
Foundation.cine until it is in the small intestine.
Source: Marla Paul
Northwestern University
3 月 19 日
Identification
Of
Regulatory
Molecule
For
Tumor
Formation Or Suppression
One of the small regulatory molecules, named microRNA-125b, is a novel regulator of p53, an
important protein that safeguards cells against cancers, Singapore and U.S. scientists report in
the March 17, 2009 issue of the journal Genes & Development.
The scientists found that during embryonic development, this microRNA keeps the level of p53
low to avoid excessive cell death.
But, if the DNA is damaged, the microRNA level is reduced to allow an increase in p53, which
eliminates damaged cells and thus prevents tumor formation.
The research was conducted with zebrafish.
"Interestingly, this microRNA is elevated in many types of human cancers, suggesting that it
may contribute to the formation of tumours by suppressing the p53 protein," said Bing Lim,
M.D., Ph.D., lead author and senior group leader at the Genome Institute of Singapore (GIS),
a research institute under the Agency for Science, Technology and Research (A*STAR).
"Hence, our findings have important implications in the diagnosis and treatment of cancers,"
he added. "The significance of this finding, of course, once again emphasizes the relevance
and importance of research linking microRNAs to many subspecialties of human medicine,
including cancer and regenerative medicine."
Harvard Medical School's Judy Lieberman, M.D., Ph.D., said, "This important study provides
an elegant and beautifully worked out example of the role of microRNAs in master-minding
how a cell responds to environmental cues and developmental signals.
"The implication of this study is that these small molecules might be mimicked or antagonized
as drugs to treat serious diseases for which no effective treatment exists at present," added Dr.
Lieberman, senior investigator at the Immune Disease Institute, and Professor of Pediatrics
and Director of the Division of AIDS at Harvard. She is not a co-author of the paper.
140
Professor of Cell Biology at the Harvard Medical School, Frank McKeon, Ph.D., commented,
"This is an elegant use of zebrafish models to uncover how a single microRNA can regulate
the p53 tumor suppressor gene. The strength of this regulation suggests that we will hear
more about the microRNA-125b in specific human cancers in the near future." Dr. McKeon
also is not a co-author of the paper
MicroRNA-125b is a member of the microRNA family of small regulatory molecules that have
evolved in nature to regulate tightly the quantity of protein produced by each messenger RNA
(mRNA), which generates the group of proteins that determine the unique characteristics of
every cell type.
MicroRNAs play complex roles in the simultaneous fine-tuning of many genes in each cell - a
role not yet well understood by biologists. It is a complicated, delicate balance that can be
profoundly disturbed if just a few microRNAs go awry.
Recent research reveals that microRNAs are abundant in the cell, and that they play important
roles in development and in many diseases.
Notes:
In addition to GIS, the institutes involved in this research work include Singapore's Institute of
Molecular and Cell Biology, also a part of A*STAR; the Singapore-MIT Alliance in Singapore;
and the Massachusetts Institute of Technology, Harvard Medical School, and Whitehead
Institute for Biomedical Research in the US.
The research findings are in the March 17, 2009 online issue of Genes & Development in an
article titled, "MicroRNA-125b is a novel negative regulator of p53."
Authors: Minh T. N. Le1,2, Cathleen Teh3,#, Ng Shyh-Chang2,#, Huangming Xie1,2,4, Beiyan
Zhou4, Vladimir Korzh3, Harvey F. Lodish1,4,5, Bing Lim1,2,6,*
1. Computation and Systems Biology , Singapore -MIT Alliance , 4 Engineering Drive 3,
Singapore 117576
2. Stem Cell and Developmental Biology, Genome Institute of Singapore , 60 Biopolis
Street , Genome , Singapore 138672
3. Fish Developmental Biology, Institute of Molecular and Cell Biology, 61 Biopolis Drive ,
Proteos , Singapore 138673
4. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Suite 601 ,
Cambridge , MA 02142 , USA
141
5. Department of Biology, Massachusetts Institute of Technology , Cambridge , MA
02142 , USA
6. CLS 442 Beth Israel Deaconess Medical Center , Harvard Medical School , 300
Brookline Ave, Boston , MA 02215 , USA
# These authors contributed equally to this paper as co-second authors.
Genome Institute of Singapore: http://www.gis.a-star.edu.sg/
The Genome Institute of Singapore (GIS) is a member of the Agency for Science, Technology
and Research (A*STAR). It is a national initiative with a global vision that seeks to use
genomic sciences to improve public health and public prosperity. Established in 2001 as a
centre for genomic discovery, the GIS will pursue the integration of technology, genetics and
biology towards the goal of individualized medicine. The key research areas at the GIS include
Systems Biology, Stem Cell & Developmental Biology, Cancer Biology & Pharmacology,
Human Genetics, Infectious Diseases, Genomic Technologies, and Computational &
Mathematical Biology. The genomics infrastructure at the GIS is utilized to train new scientific
talent, to function as a bridge for academic and industrial research, and to explore scientific
questions of high impact.
Agency for Science, Technology and Research (A*STAR): http://www.a-star.edu.sg
A*STAR is Singapore 's lead agency for fostering world-class scientific research and talent for
a vibrant knowledge-based Singapore . A*STAR actively nurtures public sector research and
development in Biomedical Sciences, Physical Sciences and Engineering, with a particular
focus on fields essential to Singapore's manufacturing industry and new growth industries. It
oversees 22 research institutes, consortia and centres, and supports extramural research with
the universities, hospital research centres and other local and international partners. At the
heart of this knowledge intensive work is human capital. Top local and international scientific
talent drive knowledge creation at A*STAR research institutes. The agency also sends
scholars for undergraduate, graduate and post-doctoral training in the best universities, a
reflection of the high priority A*STAR places on nurturing the next generation of scientific talent.
Source: Cathy Yarbrough
Agency for Science, Technology and Research (A*STAR), Singapore
3 月 20 日
Malnutrition risk underappreciated in laryngeal cancer
patients
142
ESMO Symposium on Cancer and Nutrition, Zurich, Switzerland, March 20-21, 2009
Almost half of all patients with cancer of the voice box (larynx) who
receive radiotherapy treatment will experience malnutrition, according
to new data presented at the European Society for Medical Oncology's
Symposium on Cancer and Nutrition (Zurich, 20-21 March 2009).
Larynx cancer is one of the most common head and neck cancers, with 159,000
new cases and 90,000 deaths reported worldwide each year.
"The risk of larynx cancer is greatly increased by tobacco smoking and
alcohol consumption," says researcher Jacqueline Langius from the
Department of Nutrition and Dietetics at VU University Medical Center in
Amsterdam. "Populations at high risk are therefore those where both habits
are common."
Langius and colleagues studied 238 patients with early stage laryngeal
cancer who received radiotherapy, a standard form of treatment. They found
that 44% of patients developed malnutrition, which researchers defined
as a weight loss of at least 5%.
The sub-group of patients whose cancer had spread to the lymph nodes in
their neck--or who were at high risk of such spread--were also treated
with irradiation on their neck lymph nodes. In the study almost half of
patients (48%) received irradiation on the neck nodes. The researchers
found that these patients were more than four-times as likely to become
malnourished.
Malnutrition has been linked to a wide range of physical and clinically
relevant side-effects in cancer patients, including an impaired response
to treatment, adverse reactions and reduced quality of life. Consequently,
preventing weight loss is important.
"Malnutrition is an underestimated problem in patients with early stage
larynx cancer who receive radiotherapy," Jacqueline Langius says. "To
prevent malnutrition, nutritional support should be offered to all
patients who receive nodal irradiation."
Ideally, dietary counselling should be offered by a trained dietician,
Langius says.
3 月 20 日
143
Pitt Vaccine To Prevent Colon Cancer Being Tested In
Patients
Researchers at the University of Pittsburgh School of Medicine have begun testing a
vaccine that might be able to prevent colon cancer in people at high risk for developing
the disease. If shown to be effective, it might spare patients the risk and inconvenience
of repeated invasive surveillance tests, such as colonoscopy, that are now necessary
to spot and remove precancerous polyps.
Colon cancer takes years to develop and typically starts with a polyp, which is a benign
but abnormal growth in the intestinal lining, explained principal investigator Robert
E. Schoen, M.D., M.P.H., professor of medicine and epidemiology at the University of
Pittsburgh. Polyps that could become cancerous are called adenomas.
In a novel approach for cancer prevention, the Pitt vaccine is directed against an
abnormal variant of a self-made cell protein called MUC1, which is altered and produced
in excess in advanced adenomas and cancer. Vaccines currently in use to prevent cancer
work via a different mechanism, specifically by blocking infection with viruses that
are linked with cancer. For example, Gardasil protects against human papilloma virus
associated with cervical cancer and hepatitis B vaccine protects against liver cancer.
"By stimulating an immune response against the MUC1 protein in these precancerous growths,
we may be able to draw the immune system's fire to attack and destroy the abnormal cells,"
Dr. Schoen said. "That might not only prevent progression to cancer, but even polyp
recurrence."
According to co-investigator Olivera Finn, Ph.D., professor and chair of the Department
of Immunology at Pitt's School of Medicine, MUC1 vaccines have been tested for safety
and immunogenicity in patients with late-stage colon cancer and pancreatic cancer.
"Patients were able to generate an immune response despite their cancer-weakened immune
systems," she noted. "Patients with advanced adenomas are otherwise healthy and so they
would be expected to generate a stronger immune response. That may be able to stop
precancerous lesions from transforming into malignant tumors."
About a dozen people have received the experimental vaccine so far, and the researchers
intend to enroll another 50 or so into the study. Participants must be between 40 and
70 years old and have a history of developing adenomas that are deemed advanced, meaning
they are greater than or equal to 1 centimeter in size, are typed as villous or
tubulovillous, or contain severely dysplastic, or abnormal, cells. After an initial dose
of vaccine, the participants will get shots again two and 10 weeks later. Blood samples
will be drawn to measure immune response at those time points as well as 12 weeks, 28
144
weeks and one year later.
People who develop advanced adenomas undergo regular surveillance with colonoscopy so
that recurrent polyps, which are common, can be removed before matters get worse, Dr.
Schoen said.
"Immunotherapy might be a good alternative to colonoscopy because it is noninvasive and
nontoxic," he noted. "And, it could provide long-term protection."
Colorectal cancer is the third leading cause of cancer death in the United States. In
2008, the American Cancer Society estimated that there were more than 108,000 new cases
of colon cancer, nearly 41,000 cases of rectal cancer, and almost 50,000 deaths due to
both diseases.
Pitt's colon cancer vaccine is sponsored by the National Cancer Institute and The Nathan
S. Arenson Fund for Pancreatic Cancer Research. Its adjuvant component, which enhances
the immune system's ability to respond to the target protein, was developed and provided
by Washington, D.C.-based Oncovir, Inc.
The University of Pittsburgh School of Medicine is one of the nation's leading medical
schools, renowned for its curriculum that emphasizes both the science and humanity of
medicine and its remarkable growth in National Institutes of Health (NIH) grant support,
which has more than doubled since 1998. For fiscal year 2007, the University ranked sixth
out of more than 3,000 entities receiving NIH support with respect to the research grants
awarded to its faculty. As one of the university's six Schools of the Health Sciences,
the School of Medicine is the academic partner to the University of Pittsburgh Medical
Center (UPMC). Their combined mission is to train tomorrow's health care specialists
and biomedical scientists, engage in groundbreaking research that will advance
understanding of the causes and treatments of disease and participate in the delivery
of outstanding patient care.
University of Pittsburgh Medical Center, U.S. Steel Tower, 600 Grant St., 57th Floor,
Pittsburgh, PA 15213 United States
Source
University of Pittsburgh Medical Center
3 月 20 日
Research Yields Potential Target For Cancer, Wound Healing
And Fibrosis
Research conducted by Allison Berrier, PhD, Assistant Professor of Oral and Craniofacial Biology at
145
the LSU Health Sciences Center New Orleans School of Dentistry, and colleagues, provides insights
that may help scientists design novel approaches to control wound healing and fight diseases such as
cancer and fibrosis. The paper, β1 Integrin Cytoplasmic Domain Residues Selectively Modulate
Fibronectin Matrix Assembly and Cell Spreading through Talin and Akt-1, will be published in the
March 20, 2009 issue of the Journal of Biological Chemistry. The research team also included Drs. J.
Angelo Green and Kenneth Yamada at the National Institute of Dental and Craniofacial Research, as
well as Dr. Roumen Pankov at Sofia University in Sofia, Bulgaria.
The research concerns the regulation of integrins - proteins on the surface of cells that serve dual roles
of anchoring cells within tissues and controlling cell behavior. Integrins anchor to extracellular proteins
found outside the cell and this contact regulates important cellular activities that are critical for survival,
proliferation and differentiation in both healthy tissues and tumors. Integrins are involved in the
cellular response to injury and infection and are needed to repair damaged tissue.
Of the many integrins that exist, the beta-1 integrin is of great interest because it is involved in nearly
every cell in the body. Its importance is demonstrated by the fact that mice, which are typically used as
models for disease, cannot survive without the beta-1 integrin gene.
Beta-1 integrin is a cell surface protein that spans the membrane and has a portion of the protein
outside the cell and a portion of the protein inside the cell. The beta-1 integrin tail is the portion found
inside the cell. The beta-1 integrin tail has two functions -- it connects integrins to the cellular
infrastructure and to signaling pathways.
This study advances earlier research on the beta-1 integrin tail, that revealed the ability of this integrin
tail to provide a scaffold for signaling proteins that control cell survival. The extracellular matrix is a
complex mixture containing proteins such as fibronectin and collagen that provide structural support to
cells and traction for cell movement. If cells are placed on top of extracellular matrix proteins the cells
become activated by their integrins and trigger signaling for the cell to expand or spread over the
matrix. Cell spreading is an intermediate step during cell migration on matrix proteins. Prior to the
current study it was not clear whether the beta-1 integrin tail recruits the same or different proteins
inside the cell to control two different integrin receptor functions outside the cell, namely, formation of
fibronectin fibrils and cell spreading.
The researchers generated a panel of stable cell lines containing different mutations in cells of the
beta-1 integrin tail. In the current study, the cell lines were used to determine the role of the beta-1
integrin tail in cell spreading and the production of fibronectin fibrils. Fibronectin is an anchorage
protein present in connective tissues and it helps wound healing when it is deposited in damaged tissue.
Cells can use their integrins to stretch fibronectin along their surface and this stretched or fibrillar
fibronectin provides a docking site to bind additional fibronectin and other factors involved in
inflammation and wound healing. An overabundance of fibrillar fibronectin around the cell is
characteristic of fibrosis and excessive scarring. Therefore, understanding how cells regulate the ability
of integrins to control the abundance of fibrillar fibronectin is of therapeutic interest.
These beta-1 tail mutations are thought to disrupt the ability of the beta-tail to interact with their
146
recruited proteins. The team found a defect in assembling fibronectin fibrils for the majority of the
beta-1 integrin tail mutations. Further studies focused on studying two cell lines that were both unable
to form fibrils. When adhesion to fibronectin was examined, one cell line spread whereas the other did
not. They demonstrated that specific beta-1 tail mutations can affect cell signaling, cell spreading or
formation of fibronectin fibrils. These studies revealed an ability of the cell to sort out different ways of
controlling various integrin activities. For instance, the integrin beta-1 tail specifically recruited a
protein called talin, found in this study to be important for integrins to form fibronectin fibrils, yet talin
was dispensable for early cell spreading events. This ability to selectively adjust particular functions of
the integrin may be a key to preventing the progression of diseases associated with abnormal integrin
signaling or fibronectin fibril formation such as in cancer and fibrosis.
"Based upon these studies, the aim of my current research at the LSU Health Sciences Center New
Orleans School of Dentistry focuses on those proteins that connect to integrin beta-tails in oral cancer
because this knowledge will aid in developing therapeutics that selectively target aberrant integrin
functions in oral cancer, " notes Dr. Berrier.
"Understanding the mechanisms by which the beta-1 integrin controls the many functions that it
regulates is critical to designing drugs that are specific enough to block defective functions of the
integrin while simultaneously maintaining normal activities of the integrin in healthy tissue," said Dr.
Green.
Notes:
The research was conducted at the National Institute of Dental and Craniofacial Research at the
National Institutes of Health and sponsored, in part, by the National Center on Minority Health and
Health Disparities.
LSU Health Sciences Center New Orleans educates the majority of Louisiana's health care
professionals. The state's academic health leader, LSUHSC comprises a School of Medicine, the state's
only School of Dentistry, Louisiana's only public School of Public Health, Schools of Allied Health
Professions and Graduate Studies, as well as the only School of Nursing in Louisiana within an
academic health center. LSUHSC faculty take care of patients in public and private hospitals and
clinics throughout Louisiana. In the vanguard of biosciences research in a number of areas worldwide,
LSUHSC faculty have made lifesaving discoveries and continue to work to prevent, treat, or cure
disease. LSUHSC outreach programs span the state.
Source: Leslie Capo
Louisiana State University Health Sciences Center
3 月 20 日
147
OSI Submits Supplemental New Drug Application To The FDA
For Tarceva As A First-Line Maintenance Therapy In Advanced
Non-Small Cell Lung Cancer
OSI Pharmaceuticals, Inc. (Nasdaq: OSIP) and Genentech, Inc., (NYSE: DNA) announced that
OSI submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug
Administration (FDA) for the use of Tarceva® (erlotinib) as a first-line maintenance
therapy for people with advanced non-small cell lung cancer (NSCLC) who have not
progressed following first-line treatment with platinum-based chemotherapy.
Additionally, the Companies announced that Roche, their international collaborator for
Tarceva, filed an application in Europe with the European Medicines Agency (EMEA).
"If approved, Tarceva will be the first EGFR targeted and oral therapy available as a
first-line maintenance treatment for people with NSCLC, which we believe is an important
advancement in the treatment of lung cancer," stated Colin Goddard, Ph.D., Chief
Executive Officer of OSI Pharmaceuticals.
"The FDA application reflects our goal of extending the time people with advanced lung
cancer live without their disease progressing following initial treatment with
chemotherapy," said Hal Barron, M.D., Genentech's senior vice president, Development
and chief medical officer.
Both the U.S. and EU submissions are based on a pivotal Phase III placebo-controlled,
randomized, double-blind trial known as SATURN. In November 2008, OSI, Genentech and
Roche announced that SATURN met its primary endpoint and showed that Tarceva
significantly extended the time patients with advanced NSCLC lived without their cancer
getting worse (progression-free survival or PFS) when given immediately following
initial treatment with platinum-based chemotherapy, compared to placebo. There were no
new or unexpected safety signals in the study and adverse events were consistent with
those observed in previous NSCLC clinical trials evaluating Tarceva.
The SATURN data will be presented at the 45th Annual Meeting of the American Society
of Clinical Oncology being held May 29-June 2, 2009 in Orlando, Fla. Overall survival
data, a secondary endpoint of the study, are expected in the second half of 2009 and
will be part of the FDA review process.
Additional Information about SATURN
The SATURN study, conducted by Roche, enrolled 889 patients with advanced NSCLC at
approximately 160 sites worldwide. Patients were treated with at least four cycles of
standard first-line platinum-based chemotherapy and were then randomized to Tarceva or
148
placebo if their cancer did not progress. The primary endpoint of the study was
progression-free survival. Secondary endpoints included overall survival, safety and
an evaluation of exploratory biomarkers.
About Lung Cancer
According to the American Cancer Society (ACS), lung cancer is the single largest cause
of cancer death among men and women in the U.S. and nearly 162,000 Americans died from
the disease in 2008. Most people with lung cancer are diagnosed with advanced stage
disease that cannot be surgically removed or has spread to other parts of the body. The
majority of people with advanced lung cancer survive less than one year. NSCLC is the
most common type of lung cancer.
About Tarceva
Tarceva is a small molecule designed to target the EGFR pathway, which is one of the
factors critical to cell growth in NSCLC and pancreatic cancers. Tarceva is designed
to inhibit the tyrosine kinase activity of the EGFR signaling pathway inside the cell.
Tarceva is FDA-approved for use as a monotherapy in patients with locally advanced or
metastatic NSCLC whose disease has progressed after one or more courses of chemotherapy.
Results from two, multicenter, placebo-controlled, randomized, Phase III trials
conducted in first-line patients with locally advanced or metastatic NSCLC showed no
clinical benefit with the concurrent administration of Tarceva with platinum-based
chemotherapy (carboplatin and paclitaxel or gemcitabine and cisplatin) and its use is
not recommended in that setting.
Tarceva is also approved in combination with gemcitabine for the treatment of patients
who have not received previous chemotherapy for locally advanced pancreatic cancer,
pancreatic cancer that cannot be surgically removed or pancreatic cancer that has spread
to distant body organs.
Tarceva Safety
In clinical studies, there were infrequent reports of serious lung injuries similar to
Interstitial Lung Disease (ILD)-like events including deaths. Liver and/or kidney
problems (including deaths) have been reported in some patients taking Tarceva. Patients
receiving Tarceva plus gemcitabine were more likely to experience bleeding and clotting
problems such as heart attack or stroke. Women should avoid becoming pregnant and avoid
breastfeeding while taking Tarceva. Patients taking Tarceva have experienced new or
worsening skin rash; serious or ongoing diarrhea, nausea, loss of appetite, or vomiting;
new or worsening shortness of breath or cough; fever; eye irritation. Patients should
stop smoking while taking Tarceva. Rash and diarrhea were the most common side effects
associated with Tarceva in the non-small cell lung cancer clinical study. Fatigue, rash,
149
nausea, loss of appetite, and diarrhea were the most common side effects associated with
Tarceva plus gemcitabine therapy in the pancreatic cancer clinical study.
For full prescribing information, please call 1-877-TARCEVA or visit
http://www.tarceva.com.
About OSI Pharmaceuticals
OSI Pharmaceuticals is committed to "shaping medicine and changing lives" by discovering,
developing and commercializing high-quality, novel and differentiated personalized
medicines designed to extend life and improve the quality of life for patients with cancer
and diabetes/obesity. For additional information about OSI, please visit
http://www.osip.com.
About Genentech
Founded more than 30 years ago, Genentech is a leading biotechnology company that
discovers, develops, manufactures and commercializes medicines for patients with
significant unmet medical needs. The company has headquarters in South San Francisco,
California and is listed on the New York Stock Exchange under the symbol DNA. For
additional information about the company, please visit http://www.gene.com.
OSI Safe Harbor Statement
This news release contains forward-looking statements. These statements are subject to
known and unknown risks and uncertainties that may cause actual future experience and
results to differ materially from the statements made. Factors that might cause such
a difference include, among others, OSI's and its collaborators' abilities to
effectively market and sell Tarceva and to expand the approved indications for Tarceva,
OSI's ability to protect its intellectual property rights, safety concerns regarding
Tarceva, competition to Tarceva and OSI's drug candidates from other biotechnology and
pharmaceutical companies, the completion of clinical trials, the effects of FDA and other
governmental regulation, including pricing controls, OSI's ability to successfully
develop and commercialize drug candidates, and other factors described in OSI
Pharmaceuticals' filings with the Securities and Exchange Commission.
Genentech Safe Harbor Statement
This press release contains forward-looking statements regarding the potential for
Tarceva and approval for Tarceva in the first-line maintenance setting for NSCLC. Such
statements are predictions and involve risks and uncertainties such that actual results
may differ materially. Actual results may be affected by a number of factors including,
but not limited to, unexpected safety, efficacy or manufacturing issues, the need for
additional data, data analysis or clinical studies, NDA preparation, FDA actions or
150
delays, failure to obtain or maintain FDA approval, competition, pricing, reimbursement,
the ability to supply product, product withdrawals and new product approvals and launches,
and intellectual property or contract rights. Please also refer to the risk factors
described in Genentech's periodic reports filed with the Securities and Exchange
Commission. Genentech disclaims, and does not undertake, any obligation to update or
revise any forward-looking statement in this press release.
Source
Genentech
3 月 20 日
Novogen's NV-128 Targets The MTOR Pathway To Induce Cell
Death In Epithelial Ovarian Cancer Stem Cells
NV-128, a Novogen, Ltd. (ASX: NRT) (NASDAQ: NVGN) compound, induced cell death in ovarian
cancer stem cells in a dose-dependent manner.
The study will be presented by Ayesha
Alvero, M.D., of Yale University School of Medicine, Department of Obstetrics,
Gynecology and Reproductive Science, at the 2009 Annual Meeting of the American
Association for Cancer Research in Denver, April 18-22.
Because ovarian cancer stem
cells usually survive conventional chemotherapy, these cells are considered to be the
potential source of recurrence.
It appears that NV-128 promotes cell death in these
cancer stem cells through inhibition of the mTOR and other pathways.
These findings
may open up a new avenue for treating ovarian cancer patients who become resistant to
chemotherapy.
The team from Yale University, headed by Professor Gil Mor, recently reported the
identification and characterization of the epithelial ovarian cancer stem cells using
the marker CD44 and demonstrated the up-regulation of the mTOR survival pathway in these
cells. They previously reported that the synthetic isoflavonoid compound, NV-128, is
able to specifically induce mTOR dephosphorylation resulting in inhibition of both
mTORC1 and mTORC2 activity.
In epithelial ovarian cancer cell lines NV-128 caused
substantial apoptotic cell death in mice engrafted with human ovarian cancers. NV-128
not only significantly inhibited tumor growth, but produced this effect without apparent
toxicity.
The objective of this study was to determine the cytotoxic effect of NV-128 on the ovarian
cancer stem cells.
NV-128 had a dramatic effect on the growth and differentiation of CD44+ ovarian cancer
cell lines.
CD44+ ovarian cancer stem cells were treated with increasing
concentrations of NV-128 and positive results were observed as early as 15 minutes
post-treatment.
In addition, NV-128 prevented ovarian cancer stem cell
151
differentiation in the Matrigel differentiation system.
"We are encouraged by the selective cytotoxic effects and the impact on cancer stem cells
that NV-128 demonstrated in this study in ovarian cancer," said Professor Alan Husband,
Group Director of Research for the Novogen group.
"We have observed similar selective cytotoxicity with NV-128 in non-small cell lung
cancer models and we look forward to the further clinical development of this compound
so that these aggressive diseases may be more safely and effectively treated using this
new opportunity presented by NV-128," said Professor Husband.
About NV-128
NV-128 does not rely on the traditional approach of caspase-mediated apoptosis, a death
mechanism which is not effective in cancer cells that have become resistant to
chemotherapy.
Rather, NV-128 uncouples a signal transduction cascade which has a key
role in driving protein translation and uncontrolled cancer cell proliferation. Further,
NV-128 induces mitochondrial depolarization via the novel mTOR pathway. In cancer cells,
mTOR signals enhance tumor growth and may be associated with resistance to conventional
therapies. Inhibition of mTOR appears to shut down many of these survival pathways,
including proteins that protect the mitochondria of cancer cells. Animal studies have
shown that NV-128 not only significantly retards tumor proliferation, inhibiting the
progression of ovarian cancers engrafted into mice, but produces this effect without
apparent toxicity.
This effect was shown to be due to caspase-independent pathways
involving inhibition of the mTOR pathway.
Unlike analogues of rapamycin, which target
only mTORC1, NV-128's capacity to dephosphorylate mTOR enables it to inhibit both mTORC1
and mTORC2 activity.
This blocks growth factor driven activation of AKT and the
potential for development of chemoresistance.
When NV-128 is used in combination with the Marshall Edwards, Inc., compound phenoxodiol,
apoptosis is enhanced because two pathways to cell death appear to be activated,
according to pre-clinical studies.
About Novogen Limited
Novogen Limited (ASX: NRT) (NASDAQ: NVGN) is an Australian biotechnology company based
in Sydney, Australia, that is developing a range of oncology therapeutics from its
proprietary flavonoid synthetic chemistry technology platform.
Marshall Edwards,
Inc. (NASDAQ: MSHL) is a majority owned US subsidiary of Novogen which has licensed rights
from Novogen to undertake clinical trials to bring three of its oncology drugs -phenoxodiol, triphendiol (NV-196) and NV-143 -- to market globally.
Under U.S. law, a new drug cannot be marketed until it has been investigated in clinical
trials and approved by the FDA as being safe and effective for the intended use.
152
Statements included in this press release that are not historical in nature are
"forward-looking statements" within the meaning of the "safe harbor" provisions of the
Private Securities Litigation Reform Act of 1995. You should be aware that our actual
results could differ materially from those contained in the forward-looking statements,
which are based on management's current expectations and are subject to a number of risks
and uncertainties, including, but not limited to, our failure to successfully
commercialize our product candidates; costs and delays in the development and/or FDA
approval, or the failure to obtain such approval, of our product candidates;
uncertainties in clinical trial results; our inability to maintain or enter into, and
the risks resulting from our dependence upon, collaboration or contractual arrangements
necessary for the development, manufacture, commercialization, marketing, sales and
distribution of any products; competitive factors; our inability to protect our patents
or proprietary rights and obtain necessary rights to third party patents and intellectual
property to operate our business; our inability to operate our business without
infringing the patents and proprietary rights of others; general economic conditions;
the failure of any products to gain market acceptance; our inability to obtain any
additional required financing; technological changes; government regulation; changes
in industry practice; and one-time events. We do not intend to update any of these factors
or to publicly announce the results of any revisions to these forward-looking statements.
Source
Novogen
3 月 21 日
Focus on treating malnutrition in cancer patients, researchers
say
ESMO Symposium on Cancer and Nutrition, Zurich, Switzerland, 20-21 March 2009
Cancer patients who are malnourished experience significantly greater
levels of psychological distress than those who are more adequately
nourished, according to new results reported at the European Society for
Medical Oncology's Symposium on Cancer and Nutrition (Zurich, 20-21 March
2009).
Malnutrition is a common problem in cancer. It is estimated that between
31% and 87% of cancer patients will experience weight loss and
malnutrition during the course of their disease. Such patients are left
with a poorer response to treatment, worse quality of life and reduced
survival. Yet the problem often remains undiagnosed and untreated.
153
Dr Shafia Amdouni, from the Cancer Nutrition Rehabilitation Program at
Canada's McGill University Health Center, and colleagues set out to study
the relationship between malnutrition and psychological distress in
patients who were taking part in a cancer nutrition rehabilitation
program.
They studied 213 patients with advanced cancer, asking them to assess
their own nutrition status and their distress.
Nutrition was measured using a patient-generated subjective global
assessment, which calculates a grouping of nutritional scores after
combining information from food intake, weight change, nutrition-related
symptoms, and performance status and categorizes patients into three
distinctive classes of nutritional status. Distress was measured using
a 'distress thermometer', a self-reported measure using an 11-point scale
from 0 (no distress) to 10 (extreme distress).
The researchers found that the score on the distress thermometer was
positively correlated with the total score of the patient-generated
subjective global assessment. The higher the distress, the worse the
patient's nutrition status.
"Our data suggest that nutrition status may contribute to the level of
distress in patients with cancer," Dr Amdouni says. "Evaluation of the
nutrition status should be included in the evaluation of distress
experienced by these patients."
Ideally, patients should be seen by a clinical nutritionist or a clinical
dietician, the researchers say.
###
Notes to Editors
About the European Society for Medical Oncology (ESMO)
The European Society for Medical Oncology (ESMO) is a non-profit
organization which promotes medical oncology and a multidisciplinary
approach to cancer treatment.
ESMO is a community of oncology professionals that unites key stakeholders
who share the common objective of preventing cancer, fostering a
favourable environment for scientific research, and advocating for equal
access to high quality cancer treatment. As the leading European
professional medical oncology society, ESMO offers state-of-the-art
154
educational and training programs which provide the oncology community
with a platform to disseminate the most up-to-date scientific research
and information available. ESMO's scientific journal, Annals of Oncology,
ranks among the top clinical oncology journals worldwide. ESMO is an
authoritative voice in the fight against cancer and offers consultative
expertise to oncology organizations and European authorities on important
issues related to cancer research, prevention, diagnosis, treatment and
cure.
3 月 21 日
Special gold nanoparticles show promise for 'cooking' cancer
cells
SALT LAKE CITY, March 22, 2009 — Researchers are describing a long-awaited advance
toward applying the marvels of nanotechnology in the battle against cancer. They have
developed the first hollow gold nanospheres — smaller than the finest flecks of dust — that
search out and "cook" cancer cells. The cancer-destroying nanospheres show particular
promise as a minimally invasive future treatment for malignant melanoma, the most serious
form of skin cancer, the researchers say. Melanoma now causes more than 8,000 deaths
annually in the United States alone and is on the increase globally.
The topic of a report presented here today at the American Chemical Society's 237th National
Meeting, the hollow gold nanospheres are equipped with a special "peptide." That protein
fragment draws the nanospheres directly to melanoma cells, while avoiding healthy skin cells.
After collecting inside the cancer, the nanospheres heat up when exposed to near-infrared
light, which penetrates deeply through the surface of the skin. In recent studies in mice, the
hollow gold nanospheres did eight times more damage to skin tumors than the same
nanospheres without the targeting peptides, the researchers say.
"This technique is very promising and exciting," explains study co-author Jin Zhang, Ph.D., a
professor of chemistry and biochemistry at the University of California in Santa Cruz. "It's
basically like putting a cancer cell in hot water and boiling it to death. The more heat the
metal nanospheres generate, the better."
This form of cancer therapy is actually a variation of photothermal ablation, also known as
photoablation therapy (PAT), a technique in which doctors use light to burn tumors. Since the
technique can destroy healthy skin cells, doctors must carefully control the duration and
intensity of treatment.
Researchers now know that PATs can be greatly enhanced by applying a light absorbing
material, such as metal nanoparticles, to the tumor. Although researchers have developed
various types of metal nanoparticles to help improve this technique, many materials show
poor penetration into cancer cells and limited heat carrying-capacities. These particles
155
include solid gold nanoparticles and nanorods that lack the desired combination of spherical
shape and strong near-infrared light absorption for effective PAT, scientists say.
To develop more effective cancer-burning materials, Zhang and colleagues focused on hollow
gold nanospheres — each about 1/50,000th the width of a single human hair. Previous
studies by others suggest that gold "nanoshells" have the potential for strong near-infrared
light absorption. However, scientists have been largely unable to produce them successfully
in the lab, Zhang notes.
After years of research toward this goal, Zhang announced in 2006 that he had finally
developed a nanoshell or hollow nanosphere with the "right stuff" for cancer therapy: Gold
spheres with an optimal light absorption capacity in the near-infrared region, small size, and
spherical shape, perfect for penetrating cancer cells and burning them up.
"Previously developed nanostructures such as nanorods were like chopsticks on the
nanoscale," Zhang says. "They can go through the cell membrane, but only at certain angles.
Our spheres allow a smoother, more efficient flow through the membranes."
The gold nanoshells, which are nearly perfect spheres, range in size from 30 to 50
nanometers — thousands of times smaller than the width of a human hair. The shells are also
much smaller than other nanoparticles previously designed for photoablation therapy, he
says. Another advantages is that gold is also safer and has fewer side effects in the body than
other metal nanoparticles, Zhang notes.
In collaboration with Chun Li, Ph.D., a professor at the University of Texas M.D. Anderson
Cancer Center in Houston, Zhang and his associates equipped the nanospheres with a
peptide to a protein receptor that is abundant in melanoma cells, giving the nanospheres the
ability to target and destroy skin cancer. In tests using mice, the resulting nanospheres were
found to be significantly more effective than solid gold nanoparticles due to much stronger
near infrared-light absorption of the hollow nanospheres, the researchers say.
The next step is to try the nanospheres in humans, Zhang says. This requires extensive
preclinical toxicity studies. The mice study is the first step, and there is a long way to go
before it can be put into clinical practice, Li says.
###
The U.S. Department of Defense and the National Science Foundation funded the research in
Zhang's lab while the National Institutes of Health funded the work in Dr. Li's lab.
The American Chemical Society is a nonprofit organization chartered by the U.S. Congress.
With more than 154,000 members, ACS is the world's largest scientific society and a global
leader in providing access to chemistry-related research through its multiple databases,
peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C.,
and Columbus, Ohio.
156
3 月 21 日
New Study Reveals Genetic Link To Blood Cancers
The study, published in the journal Nature Genetics, has shown that susceptibility to a series of
blood cancers, known as myeloproliferative disorders (MPDs), is linked to a particular area of
the patient's DNA, which is prone to developing mutations.
Myeloproliferative disorders are characterised by the overproduction of red and white blood
cells, which increases the risk of strokes and heart attacks. Many cases of MPDs are caused
by a mutation in a gene called JAK2. When the JAK2 gene has mutated, it sends abnormal
messages to the blood stem cells to produce more and more blood cells.
Scientists, funded by Leukaemia Research, have found that a particular region of chromosome
9 that carries the JAK2 gene is predisposed to acquiring mutations, but only in individuals with
a particular genetic makeup. It is likely that this finding will lead to a much better understanding
of how the JAK2 gene mutations happen and why they lead to an increased risk of someone
developing an MPD.
The study, carried out at the Wessex Regional Genetics Laboratory in Salisbury and the
University of Southampton, has proved that people carrying this mutation-prone region of DNA
on chromosome 9 that includes the JAK2 gene have triple the risk of developing an MPD.
The chromosome 9 variant is present in 40 per cent of the UK population but only 1 in 20,000
people develop an MPD each year. Nonetheless, the new research has confirmed that the
inheritance of this genetic variant can contribute to inherited susceptibility to develop an MPD.
The study found that the link was especially strong in polycythaemia vera (PV), one of the
main three MPDs. Professor Nick Cross, from the University of Southampton who led the
research team, says: "This research provides strong evidence that at least half of the cases of
PV diagnosed each year are linked to an inherited genetic variant on chromosome 9. Whilst
this risk is still very small it nonetheless confirms that individual susceptibility to acquiring
cancer-causing mutations is linked to genetic inheritance. Now that we have this evidence we
can carry out studies to determine exactly how the variant contributes to this risk."
Dr Shabih Syed, Scientific Director at Leukaemia Research, adds: "This is a very important
step forward in our knowledge of the causes of myeloproliferative disorders. It helps us to
understand why some people might be predisposed to acquiring genetic mutations that lead to
cancers."
The report is published online from 15 March 2009 in the journal Nature Genetics under the
title 'JAK2 haplotype is a major risk factor for the development of myeloproliferative
neoplasms'. The corresponding author is Professor Nicholas Cross of the Human Genetics
Division, University of Southampton and the Wessex Regional Genetics Laboratory, Salisbury.
157
The study was funded by the cancer charity Leukaemia Research.
Southampton University
http://www.soton.ac.uk
3 月 21 日
Another LNA-based RNA Inhibitor Enters Clinical Trials
Santaris Pharma announced that the fourth LNA-based drug has been brought into the clinic.
In the USA several patients with cancer have now been treated with the Company's Survivin
inhibitor, which is jointly developed by Santaris Pharma and Enzon Pharmaceuticals. The U.S.
Food
and
Drug
Administration
(FDA)
recently
accepted
Enzon
Pharmaceutical's
Investigational New Drug (IND) application for the use of the LNA-based Survivin inhibitor.
Survivin is a key protein that controls cancer growth by playing a significant role in cell division,
as well as inhibiting the programming that controls cell death. The Survivin inhibitor was
developed using the Locked Nucleic Acid technology. In preclinical animal studies, EZN-3042
inhibited Survivin expression and tumor growth. It also potentiated the antitumor activity of
taxol, an approved cancer therapeutic.
"Survivin is considered one of the most promising cancer targets and we are pleased that we
were able to quickly advance this important compound into patients," said Jeffrey H. Buchalter,
chairman and chief executive officer of Enzon Pharmaceuticals.
EZN3042 is one of eight LNA-based RNA inhibitors being developed by Santaris Pharma and
Enzon Pharmaceuticals through a comprehensive partnership within the therapeutic area of
cancer. Another compound forming part of the collaboration, EZN2968, an LNA-based hif1alfa
inhibitor, is currently being investigated in two Phase I/II trials against a variety of cancers.
Under the terms of the agreement, Enzon will have exclusive rights to develop and
commercialize these compounds in the U.S. and other non-European territories. Santaris
Pharma will retain exclusive rights to commercialization in Europe.
"This is the fourth LNA-based drug that has been brought into the clinic in record time either by
ourselves or by a partner of ours based on our highly effective Drug Discovery Engine," said
Henrik 0rum, CSO at Santaris Pharma. "We are very pleased by the achievement of this
milestone and look forward to seeing other new LNA-based compounds advance into clinical
trials across a range of therapeutic areas in the near future."
At the Association for Cancer Research (AACR) meeting being held April 18-22, 2009 in
Colorado, Enzon Pharmaceuticals will present data on EZN3042 as well as on new LNA
targets. Abstracts related to those targets are now available on http://www.aacr.org.
"Novel releasable PEG-nanoparticles enhance delivery of RNA antagonist oligonucleotides in
tumor cells and in mice"
158
"EZN-2208, a novel pegylated SN-38 drug conjugate, markedly inhibits tumor growth and
metastatic spreading of human neuroblastoma"
"Androgen receptor (AR) down regulation by locked nucleic acid antisense oligonucleotides
specifically inhibits the growth of AR-positive tumor cells"
"The antitumor activity of EZN-4150, a potent LNA-based PIK3CA antagonist"
"EZN-3042, a novel locked nucleic acid oligonucleotide against survivin, inhibits survivin
expression and confers taxol sensitivity"
"EZN-3920, an LNA antisense oligonucleotide RNA antagonist, down modulates HER3
expression and PI3K/Akt signaling pathway and enhances antiproliferative effect of Gefitinib in
tumor cells"
About Santaris Pharma
Santaris Pharma is a privately held biopharmaceutical company with exclusive rights to use
the LNA Drug Platform to develop new classes of RNA medicines targeting mRNAs and
miRNAs associated with disease. The Company's own research and development activities
focus on microRNAs, infectious diseases and metabolic disorders. In addition, Santaris
Pharma is leveraging its highly effective and efficient drug discovery engine to generate lead
LNA drug candidates against a broad array of disease targets selected by strategic partners.
Santaris Pharma was founded in 2003 and the Company and its corporate partners currently
have four compounds in clinical development and a full pipeline in late preclinical development.
Current partners are Enzon Pharmaceuticals, GlaxoSmithKline and Wyeth Pharmaceuticals.
Santaris Pharma has since its inception raised nearly $100 million through private financing
and up front payments.
About Enzon
Enzon Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to developing,
manufacturing and commercializing important medicines for patients with cancer and other
life-threatening conditions. The Company has a portfolio of four marketed products,
Oncaspar(R), DepoCyt(R), Abelcet(R) and Adagen(R). Enzon's drug development programs
utilize several cutting-edge approaches, including its industry-leading PEGylation technology
platform and the Locked Nucleic Acid (LNA) technology. Enzon's PEGylation technology was
used to develop two of its products, Oncaspar and Adagen, and has created a royalty revenue
stream from licensing partner-ships for other products developed using the technology. Enzon
also engages in contract manufacturing for several pharmaceutical companies to broaden the
Company's revenue base.
3 月 21 日
159
New Evidence Points To An Overlooked Risk Factor For Cancer:
Acetaldehyde In Alcohol
New evidence by researchers at the Centre for Addiction and Mental Health (CAMH) and
researchers in Germany shows that drinking alcohol is the greatest risk factor for
acetaldehyde-related cancer. Heavy drinkers may be at increased risk due to exposure from
multiple sources.
Acetaldehyde is ubiquitous in daily life in Ontario. Widely present in the environment, it is
inhaled from the air and tobacco smoke, ingested from alcohol and foods, and produced in the
human body during the metabolism of alcoholic beverages. Research indicates that this
organic chemical plays a significant role in the development of certain types of cancers
(especially of the upper digestive tract), and it is currently classified as possibly carcinogenic
by the International Agency for Research on Cancer of the World Health Organization. New
research from CAMH in Toronto and the Chemical and Veterinary Investigation Laboratory
Karlsruhe (CVUA) in Germany recently provided the necessary methodology for calculating
the risk for the ingestion of alcoholic beverages.
The team found that risk from ingesting acetaldehyde via alcoholic beverages alone may
exceed usual safety limits for heavy drinkers. Their risk assessment study found that the
average exposure to acetaldehyde from alcoholic beverages resulted in a life-time cancer risk
of 7.6/10,000, with higher risk scenarios (e.g. contaminations in unrecorded alcohol) in the
range of 1 in 1,000. As such, the life-time cancer risks for acetaldehyde from ingestion of
alcoholic beverages greatly exceed the usual limits for cancer risks from the environment.
The research team noted, however, that this risk is compounded by the addition of
acetaldehyde exposure from different sources. "The problem with acetaldehyde has been that
although it has been recognized as toxic by Health Canada some years ago, most risk
assessments to date were based on one source of exposure only" explained Dr. Jürgen Rehm,
the lead scientist of the Toronto group and head of the Public Health and Regulatory Policies
section at CAMH. "This has led to a negligence of the overall risk."
For example, in Toronto, even though there are limits for air exposure of acetaldehyde set by
the responsible Public Health agency, these limits have been surpassed in the past. Alone, the
risks associated with surpassing limits of acetaldehyde from the air may not yet be alarming,
but for heavy drinkers and smokers, it adds to the acetaldehyde levels already received from
these sources. This overall risk then surpasses established safety limits.
"Their risk assessment of acetaldehyde present as a congener in alcoholic beverages touches
the tip of the iceberg," according to a Commentary on the CAMH/CVUA study in the journal
Addiction.
160
Based on their study the scientists of CAMH recommend:
 That the classification of acetaldehyde with respect to
cancer be re-examined, incorporating new evidence
which points to an additional cancer risk to humans.
 That a further risk assessment should take into
consideration all sources of exposure from this
substance.
 That the risk for cancer stemming from acetaldehyde
from alcoholic beverages is recognized, and
necessary preventive steps are taken to reduce the
acetaldehyde content in alcoholic beverages.
 That the overall level of acetaldehyde exposure be
minimized to the lowest level technically possible.
Notes:
Lachenmeier, D.W., Kanteres, F., Rehm, J.
Carcinogenicity of acetaldehyde in alcoholic beverages: risk assessment outside ethanol
metabolism.
Addiction
2009; 104: 533 - 550
The Centre for Addiction and Mental Health (CAMH) is Canada's largest mental health and
addiction teaching hospital, as well as one of the world's leading research centres in the area
of addiction and mental health. CAMH combines clinical care, research, education, policy
development and health promotion to transform the lives of people affected by mental health
and addiction issues.
CAMH is fully affiliated with the University of Toronto, and is a Pan American Health
Organization/World Health Organization Collaborating Centre.
Addiction is a monthly scientific journal, read in over sixty countries and publishing more than
2000 pages every year. Owned by the Society for the Study of Addiction, it has been in
continuous publication since 1884. Addiction publishes peer-reviewed research reports on
alcohol, illicit drugs and tobacco, bringing together research conducted within many different
disciplines, as well as editorials and other debate pieces.
Source: Michael Torres
Centre for Addiction and Mental Health
3 月 21 日
161
For Extraordinary Contributions To Interventional Radiology,
Society Of Interventional Radiology Honors Dotter Lecturer
Matthew A. Mauro, M.D., FSIR, delivered the 2009 Dr. Charles T. Dotter Lecture at the Society
of Interventional Radiology's 34th Annual Scientific Meeting last week in San Diego, Calif. This
award, supported by the SIR Foundation, honors an interventional radiologist's extraordinary
contributions to the field, dedicated service to SIR and distinguished career achievements in
interventional radiology.
Mauro, who addressed "The Birth of a Specialty," is the Ernest H. Wood Distinguished
Professor of Radiology and Surgery and chair of the radiology department at the University of
North Carolina at Chapel Hill School of Medicine. He was selected the recipient of the 25th
annual Dotter lecture by 2008 SIR President John Kaufman, M.D., FSIR. This lecture award
honors one of the founding fathers of interventional radiology, Dr. Charles T. Dotter.
At UNC, Mauro's special interests include interventional oncology, uterine artery embolization,
the management of vascular malformations, angioplasty and stenting, biliary drainage
procedures, embolization and stent grafts. He also supervises the resident rotation in
vascular/interventional radiology; his involvement with the residency program includes lectures
and one-on-one contact with the residents.
Mauro is a long-time SIR member; he served as president of the society from 1999 to 2000
and was chair of the SIR Foundation from 2002. He has actively participated in a variety of
roles on the Executive Committee throughout his membership and on the Scientific Program
Committee since 2000. He is chair of the American College of Radiology's Committee on
Interventional Radiology and a member of its Board of Chancellors. He is a trustee of the
American Board of Radiology.
A member and fellow of numerous radiological societies, Mauro has published more than 120
peer-reviewed articles and 30 book chapters and has served as a visiting professor/lecturer
more than 200 times. His most recent work, the textbook "Image Guided Interventions," was
published in 2008. The 2008 SIR president indicated that Mauro "has been - and continues to
be - one of the most influential leaders in interventional radiology and radiology. I can think of
no one more deserving of this honor."
2009 SIR Gold Medal Recipients
In addition, three individuals - Andreas Adam, MB, BS, FRCR, FSIR; Vincent P. Chuang, M.D.,
FSIR; and Thomas A. Sos, M.D., FSIR - were each awarded the society's Gold Medal, an
honor that is given to those who have helped ensure the future of interventional radiology by
advancing the quality of medicine and patient care.
Andreas Adam, MB, BS, FRCR, FSIR, professor of interventional radiology at the University
162
of London and honorary consultant radiologist at Guy's and St. Thomas' Hospital, has worked
tirelessly throughout his career to promote interventional radiology around the world - lecturing
extensively, publishing research in top medical journals and serving in prominent leadership
positions at interventional radiology societies.
He has served as president of several European radiological societies and, in these roles, has
worked to develop and maintain a strong collaborative relationship among interventional
radiology societies around the world, especially in Europe, North America and Asia. Invited to
give the prestigious Charles T. Dotter Lecture in 2006, Adam has served as editor for several
radiological journals and on the editorial board of numerous others.
Vincent P. Chuang, M.D., FSIR, is head and a vice president of the Angiography and
Interventional Oncoradiology Section of the Sun Yat-Sen Cancer Center in Taipei, Taiwan.
Chuang's early research was centered on angiographic diagnosis and, later, on embolization
of various forms of internal organ bleeding, particularly splenic, renal and gastric bleeding. As
chief of the angio section at the University of Texas M.D. Anderson Cancer Center in Houston,
his next stage of research was to extend transcatheter arterial embolization and superselective
catheterization technique into chemoembolization for liver tumor and transcatheter
intra-arterial chemotherapy for various regional malignant tumors. He also collaborated on
research for interventional procedures for peripheral arterial disease at Emory University
Hospital in Atlanta, Ga. He then headed the Interventional Oncology Section at the Koo
Foundation of the Sun Yat-Sen Cancer Center. During his career, he has mentored more than
100 fellows.
Thomas A. Sos, M.D., FSIR, a professor and vice chair of radiology at Weill Cornell Medical
College as well as director of peripheral arterial disease at Weill Cornell Vascular, is widely
regarded as one of the world's top authorities in both renal angioplasty and stenting. Sos has
designed numerous devices for interventional radiology, including the first microcatheter, the
"Sos Open-ended Guidewire," the first shaped embolization coil, the "Tornado," the "Viper"
small vessel PTA catheter and the "Omni" series of selective and flush catheters.
His early scientific contributions were related largely to cardiac and coronary angiography.
Once angioplasty was introduced, Sos became a leader in percutaneous renal and below
knee angioplasty. He served as president of SIR from 1986� and spent much of his career
training fellows who are now contributors to interventional radiology.
2009 Leaders in Innovation Award
Sidney Wallace, M.D., FSIR, who had served as a professor of radiology; chairman,
Department of Diagnostic Radiology; head, Division of Diagnostic Imaging and deputy division
head for research, Division of Diagnostic Imaging, at the University of Texas M.D. Anderson
Cancer Center in Houston before retiring in 1996, was awarded the 2009 Leaders in
Innovation Award by the SIR Foundation. This award acknowledges those individuals who
163
have conceptualized and implemented an idea that has had an advantageous impact on the
practice of interventional radiology.
Throughout his career, Wallace has been instrumental in advancing the knowledge and
techniques used in interventional radiology around the world. He was one of the first to
recognize interventional radiology's unique role and has been an advocate for supervising
patient care and taking an active role in the decision-making process. He has also been a
staunch supporter of the role of research in interventional radiology and is one of the founders
of the John S. Dunn Research Foundation Center for Radiologic Sciences at the University of
Texas M.D. Anderson Cancer Center. He has authored and coauthored 643 scientific papers
and chapters and holds 36 patents for devices and pharmaceutical agents.
Dr. Gary J. Becker Young Investigator Award
The SIR Foundation announced Filip Banovac, M.D., of Georgetown University Hospital in
Washington, D.C., as the recipient of the 2009 Dr. Gary J. Becker Young Investigator Award.
This award promotes excellence in academic research for members early in their careers and
honors the founding editor of the Journal of Vascular and Interventional Radiology by
recognizing the importance of the young investigator in developing interventional solutions for
the future.
Banovac's manuscript, "Radiofrequency Ablation of Lung Tumors in Swine Assisted by a
Navigation Device With Preprocedural Volumetric Planning," was chosen as the best fit model
of promoting academic research among young interventional radiologists.
Notes:
For more information about these awards or to learn more about interventional radiology, visit
online at www.SIRweb.org and www.SIRFoundation.org.
About the Society of Interventional Radiology
Interventional radiologists are physicians who specialize in minimally invasive, targeted
treatments. They offer the most in-depth knowledge of the least invasive treatments available
coupled with diagnostic and clinical experience across all specialties. They use X-ray, MRI and
other imaging to advance a catheter in the body, such as in an artery, to treat at the source of
the disease internally. As the inventors of angioplasty and the catheter-delivered stent, which
were first used in the legs to treat peripheral arterial disease, interventional radiologists
pioneered minimally invasive modern medicine.
Today many conditions that once required surgery can be treated less invasively by
interventional radiologists. Interventional radiology treatments offer less risk, less pain and less
recovery time compared to open surgery. Visit www.SIRweb.org.
164
About the Society of Interventional Radiology Foundation
SIR Foundation is a scientific foundation dedicated to fostering research and education in
interventional radiology for the purposes of advancing scientific knowledge, increasing the
number of skilled investigators in interventional radiology and developing innovative therapies
that lead to improved patient care and quality of life. Visit www.SIRFoundation.org.
Source: Maryann Verrillo
Society of Interventional Radiology
3 月 22 日
Malnutrition Risk Underappreciated In Laryngeal Cancer
Patients
Almost half of all patients with cancer of the voice box (larynx) who receive radiotherapy
treatment will experience malnutrition, according to new data presented at the European
Society for Medical Oncology's Symposium on Cancer and Nutrition (Zurich, 20-21 March
2009).
Larynx cancer is one of the most common head and neck cancers, with 159,000 new cases
and 90,000 deaths reported worldwide each year.
"The risk of larynx cancer is greatly increased by tobacco smoking and alcohol consumption,"
says researcher Jacqueline Langius from the Department of Nutrition and Dietetics at VU
University Medical Center in Amsterdam. "Populations at high risk are therefore those where
both habits are common."
Langius and colleagues studied 238 patients with early stage laryngeal cancer who received
radiotherapy, a standard form of treatment. They found that 44% of patients developed
malnutrition, which researchers defined as a weight loss of at least 5%.
The sub-group of patients whose cancer had spread to the lymph nodes in their neck--or who
were at high risk of such spread--were also treated with irradiation on their neck lymph nodes.
In the study almost half of patients (48%) received irradiation on the neck nodes. The
researchers found that these patients were more than four-times as likely to become
malnourished.
Malnutrition has been linked to a wide range of physical and clinically relevant side-effects in
cancer patients, including an impaired response to treatment, adverse reactions and reduced
quality of life. Consequently, preventing weight loss is important.
"Malnutrition is an underestimated problem in patients with early stage larynx cancer who
receive radiotherapy," Jacqueline Langius says. "To prevent malnutrition, nutritional support
should be offered to all patients who receive nodal irradiation."
165
Ideally, dietary counselling should be offered by a trained dietician, Langius says.
About the European Society for Medical Oncology (ESMO)
The European Society for Medical Oncology (ESMO) is a non-profit organization which
promotes medical oncology and a multidisciplinary approach to cancer treatment.
ESMO is a community of oncology professionals that unites key stakeholders who share the
common objective of preventing cancer, fostering a favourable environment for scientific
research, and advocating for equal access to high quality cancer treatment. As the leading
European professional medical oncology society, ESMO offers state-of-the-art educational and
training programs which provide the oncology community with a platform to disseminate the
most up-to-date scientific research and information available. ESMO's scientific journal,
Annals of Oncology, ranks among the top clinical oncology journals worldwide. ESMO is an
authoritative voice in the fight against cancer and offers consultative expertise to oncology
organizations and European authorities on important issues related to cancer research,
prevention, diagnosis, treatment and cure.
Meeting venue
The ESMO Symposium on Cancer and Nutrition will take place at the Mövenpick Hotel
Zurich - Airport
Services for media representatives
Representatives from the press will have access to all the scientific sessions and the
possibility to schedule one-on-one interviews with top speakers and presenters of the studies,
both in presence and remotely. Please contact the ESMO Press Office at media@esmo.org to
already find out about the preliminary timetable or to book a telephone hook up. The
conference
full
program
is
available
at
http://www.esmo.org/events/nutrition-2009/program.html
3 月 22 日
AngioChem's ANG1005 Shows Promise In The Treatment Of
Brain Cancers
AngioChem, a biotechnology company discovering and developing drugs that are uniquely
capable of crossing the blood-brain barrier, today announced the presentation of preliminary
safety and tolerability data for its lead drug candidate, ANG1005, from two separate Phase 1/2
studies in patients with recurrent malignant glioma and in patients with advanced solid tumors
and brain metastases. The data demonstrated that ANG1005 has a favorable safety and
tolerability profile, as evidenced by laboratory and neurocognitive data, and does not show
evidence of eliciting an immune response. Additionally, the company presented preclinical
166
data demonstrating the compound's unique ability to cross the blood-brain barrier to effectively
deliver potent therapeutic doses. These data were presented in poster sessions at the
Fifteenth Annual Blood-Brain Barrier Consortium Meeting in Oregon, being held March 19 to
21, 2009.
ANG1005 is a novel taxane derivative with the structure of an engineered peptide compound
(EPiC) that is designed to cross the blood-brain barrier (BBB) by receptor-mediated
transcytosis, overcoming the BBB's normal function of blocking foreign substances which
prevents more than 95 percent of all drugs from reaching the brain.
"We are highly encouraged by these findings -- particularly the preliminary clinical efficacy data
which has shown encouraging tumor responses -- which illustrate the unique ability of
ANG1005 to successfully cross the BBB to treat brain cancers," said Jean-Paul Castaigne,
M.D., President and Chief Executive Officer of AngioChem. "We look forward to presenting
additional efficacy data from the Phase 1/2 studies of ANG1005 at a medical meeting in April,
as well as advancements with product programs in our pipeline for other brain diseases and
disorders."
Key findings from the clinical and preclinical studies presented at the Fifteenth Annual
Blood-Brain Barrier Consortium Meeting include:
- ANG1005 showed a favorable safety and tolerability profile based on data for all 63 study
patients dosed to date in the Phase1/2 studies;
- Adverse events were manageable and less severe than those engendered by paclitaxel in
comparable dosages and included neutropenia and leucopenia;
- Data available from 31 study patients in the Phase1/2 studies indicated that ANG1005 does
not elicit an immune response, as measured by Enzyme-Linked ImmunoSorbent Assays
(ELISA);
- Neurocognitive data available for 18 patients in the Phase1/2 studies showed that ANG1005
does not show evidence of central nervous system toxicity;
- ANG1005 successfully and rapidly crossed the BBB into the brain tissues at a rate 100 times
greater than paclitaxel and distributed homogeneously across all the brain regions; and,
- ANG1005 caused a regression of tumor size in rats as opposed to a progression in two
control groups.
About ANG1005
ANG1005 is a novel taxane engineered peptide compound (EPiC) that is designed to cross the
BBB. Studies have shown that ANG1005 gains entry into the brain compartment by targeting
167
the low-density lipoprotein receptor-related protein (LRP) which is one of the most highly
expressed receptors on the surface of the BBB. Once inside the brain, ANG1005 enters tumor
cells using the same receptor-mediated pathway through LRP, which is upregulated in various
cancer cells including malignant glioma and metastatic cancers in the brain.
ANG1005 is currently being evaluated in two separate Phase 1/2 multicenter, open-label, dose
escalation studies to explore the maximum tolerated dose and obtain data on safety,
tolerability and preliminary evidence of efficacy in patients with recurrent malignant glioma and
in patients with advanced solid tumors and brain metastases. For recurrent malignant gliomas
and metastatic brain cancer, treatment options for patients are limited and prognoses are
dismal.
Phase 1/2 studies of ANG1005 in patients with primary and secondary brain cancers
demonstrated that ANG1005 has an excellent safety and tolerability profile, as evidenced by
laboratory and neurocognitive data, and does not show evidence of eliciting an immune
response in humans.
About AngioChem
AngioChem is a clinical-stage biotechnology discovering and developing new breakthrough
drugs that are uniquely capable of crossing the blood-brain barrier to treat brain diseases.
These new Engineered Peptide Compounds (EPiC) have the potential to address significant
medical needs, many of which cannot be effectively addressed due to the fundamental
physiological challenge the blood-brain barrier presents for therapeutic intervention.
AngioChem's lead product candidate, ANG1005, is in two separate Phase 1/2 clinical studies
in patients with primary brain cancers and in cancer metastases. Additionally, AngioChem is
developing a deep and broad product pipeline, including small and large molecules, for the
treatment of a wide range of brain diseases and related disorders, including brain cancer,
cancer metastases, psychiatric disorders, neurodegenerative and metabolic diseases.
Founded in 2006, AngioChem maintains headquarters in Montreal, Canada.
3 月 23 日
Former
Irish
President
Mary
Robinson
To
Chair
LIVESTRONG(TM) Global Cancer Summit
The Lance Armstrong Foundation (LAF) announced that Mary Robinson, the first female
President of Ireland and former United Nations High Commissioner for Human Rights, will
serve as Honorary Chairperson of the LIVESTRONG Global Cancer Summit. The Summit, to
be held in Dublin, Ireland August 24-26, 2009, is the landmark event of the LIVESTRONG
Global Cancer Campaign, an initiative to address the burden of cancer worldwide. The Summit
will bring together world leaders, non-governmental organizations, corporate leaders and
individuals who are making new commitments to cancer control.
"I have always viewed healthcare as a fundamental issue of human rights. It is estimated that
168
about one-third of cancers can be cured if detected and treated early," said Robinson. "It is up
to all of us -- governments, non-governmental organizations, cancer survivors, all concerned
individuals -- to see that detection and treatment are offered to as much of the world's
population as possible. Through the LIVESTRONG Global Cancer Summit we will make great
strides towards making this a reality."
Lance Armstrong Foundation President and CEO Doug Ulman said, "Mary Robinson
embodies the LIVESTRONG spirit of selfless service and leadership for the sake of positive
change in our world. She has been a tireless advocate for issues at the intersection of health
and human rights throughout her career -- and we share the view that cancer control is at its
core an issue of human rights."
The LIVESTRONG Global Cancer Summit will make the case for urgent action to address the
global cancer burden and introduce new commitments for cancer control by bringing together
world leaders, corporations, non-governmental organizations and advocates in an
unprecedented show of solidarity. Australian Prime Minister Kevin Rudd, Mexican President
Felipe Calderon Hinojosa and former U.S. President Bill Clinton are included in the list of
leaders expressing support for the Campaign and Summit, along with the Irish government
and the Irish Cancer Society. The LAF is also in ongoing conversations with the Kingdom of
Jordan and representatives of other nations about substantial new commitments.
Commitments are critical to avoid a looming public health catastrophe. Cancer kills more
people every year than AIDS, tuberculosis and malaria combined. It is estimated that cancer
will be the leading cause of death worldwide by 2010. However, many governments devote
few resources to fighting cancer and collect little information about its causes and effects. The
LAF is working with world leaders to focus on developing international partnerships, cancer
advocacy, research and data collection.
"In 2010, cancer will be the leading cause of death worldwide. The LIVESTRONG Global
Cancer Summit is an invaluable opportunity to stand up for the 28 million cancer survivors
worldwide and to create a unified effort to control cancer through new commitments to action.
This is not just a job for governments and medical researchers -- it's everyone's job," Ulman
said.
The secondary purpose of the Summit is to build a global grassroots advocacy movement to
influence global action in the fight against cancer. Participation in the Summit is by invitation
only. LAF has outlined a commitment process that all world leaders and representatives from
non-governmental organizations and corporations are required to complete to be eligible for
invitation. For more information about the LIVESTRONG Global Cancer Campaign or the
commitment process, visit http://www.LIVESTRONG.org.
Following its successes in Australia, California and Mexico, the LIVESTRONG Global Cancer
Campaign will head to Europe for the Giro d'Italia (May 9-31), the Tour de France (July 4-26),
the Tour of Ireland (Aug. 19-23) and the LIVESTRONG Global Cancer Summit in Ireland (Aug.
169
24-26), as well as other locations to be announced soon.
About the Lance Armstrong Foundation
At the Lance Armstrong Foundation, we fight for the 28 million people around the world living
with cancer today. There can be -- and should be -- life after cancer for more people. That's
why we kick in at the moment of diagnosis, giving people the resources and support they need
to fight cancer head-on. We find innovative ways to raise awareness, fund research and end
the stigma about cancer that many survivors face. We connect people and communities to
drive social change, and we call for state, national and world leaders to help fight this disease.
Source
Lance Armstrong Foundation
3 月 23 日
Latest Data On UK Cancer Survival Fuel Debate Over
Effectiveness Of NHS Cancer Plan For England
The National Health Service (NHS) cancer plan for England shows some beneficial effect on
survival, although wide regional variations remain; more follow-up data are needed before the
true impact of the cancer plan can be fully established. These are the conclusions of the first
study to assess whether the cancer plan is working, published in an Article Online First and in
the April issue of The Lancet Oncology.
In an accompanying Reflection and Reaction comment, Karol Sikora (CancerPartnersUK)
states that, despite the tripling of investment in cancer care in the UK over the past decade,
these findings show that there has been no striking improvement in cancer survival. According
to a Leading Edge editorial published with the Article by The Lancet Oncology, the evidence
shows that: "We are at best keeping track with improvements elsewhere rather than closing
the gap." The editorial adds that the cancer plan's stated aim - of having five year cancer
survival rates comparable with the best in Europe by 2010 - is looking optimistic.
In 2000, when the NHS cancer plan for England was introduced, Britain had one of the poorest
levels of cancer survival in Europe. The plan was designed to improve 5-year survival rates for
cancer, so they would compare with the best in Europe by 2010. In Wales there was no
comparable cancer initiative until 2006, thus providing an opportunity to compare survival
trends in England and Wales and assess the effectiveness of the English cancer plan.
In this study, Michel Coleman from the Cancer Research UK Cancer Survival Group London
School of Hygiene and Tropical Medicine in London, UK, and colleagues report the national
and regional survival trends in 2•2 million adults diagnosed with 21 common cancers in
England and Wales and followed up to 2007. They analysed trends in short-term survival for
patients diagnosed before the cancer plan (1996-2000), during initialisation (2001-03), and
170
after implementation (2004-06).
Overall, 1-year survival* improved for most cancers in England and Wales between 1996 and
2006. Findings showed a slightly faster improvement in 1-year survival in Wales than in
England between 1996 and 2003, but this was reversed after 2004 when annual trends in
survival were more favourable in England than in Wales. For cancers of the stomach, colon,
rectum, uterus, ovary, and kidney, survival trends in England improved after 2001, even
without screening or the widespread use of effective new treatments. By contrast, bladder
cancer, Hodgkin's lymphoma, and leukaemia all showed a fall in survival.
However, differences in 3-year survival patterns between England and Wales were less
obvious, with no difference in survival trends at 3 years or more for patients diagnosed up to
2003, and slightly faster increase in survival in England than in Wales between 2001-03 and
2004-06.The authors also note continued wide regional variation in survival, with more affluent
southern regions having generally higher survival than the average survival for England.
They suggest that the improvements in survival trends in England since 2004 might be related
to the cancer plan, but caution that it is not known whether the various initiatives in the cancer
plan were fully implemented by that time. They conclude by calling for detailed analysis of the
effect of more specific measures in the cancer plan, such as shorter waiting times and the
creation of multidisciplinary teams, on cancer survival.
Mike Richards, the National Cancer Director for England, questions whether Wales is an
appropriate control group for assessing progress in England in a second accompanying
Reflection and Reaction comment. He points out that both countries took very similar
approaches to cancer control by implementing cancer strategies that have worked at different
times. He suggests that the differences in trends between the countries in 2001-03 and
2004-06 reflect Wales moving forward faster in the earlier years as a result of the Cameron
report in 1996, and survival improving more quickly in England after 2000 as a result of the
cancer plan.
Sikora also argues that the modest improvement in survival is because of: "a whole system
fault within the NHS with serial delays, poor access and serious under-capacity." He concludes:
"We need to derive value from cancer services by increasing access and quality but not cost".
The Lancet Oncology editorial concludes that: "Perhaps the time has come to consider rather
more fundamental changes to the NHS than are offered in the cancer plan if England is to truly
offer world-class healthcare."
*1-year survival can be considered to reflect early or late diagnosis of cancer, and 3-year and
5-year survival to reflect both early diagnosis and the effect of treatment.
3 月 23 日
Pioneering Cancer Prevention Program Launched In New York
A prevention program serving an ethnically diverse population of women at high risk of cancer
171
is detailed in an article published Monday 23 March in the online peer-reviewed journal
ecancer.
The article describes a screening program to identify women from underserved communities
who are at a high risk of developing breast or ovarian cancer; a pilot clinical research initiative
sponsored by The Lynne Cohen Cancer Screening and symposium Project for High Risk
Women.
Despite the advances in cancer diagnosis, treatment, and survival, racial and ethnic minorities
suffer disproportionately from cancer. Ethnic and racial minorities are often less likely to take
part in screening programs than Caucasian patients.
The pilot project will constitute the core of a broad-based screening program in New York City
and, ultimately, a world class Clinical service targeted to women at high risk for cancer, in
particular, women of minority ethnic groups.
Dr Franco M. Muggia, Director of Medical Oncology at NYU's Langone medical Center will
conduct the study at the Kaplan Cancer Center facilities. At Bellevue Hospital, the advanced
services will be offered to 75 to 100 women who do not have access to normal medical
screenings. Women referred to the program will receive state-of-the-art preventive care and
early detection screening.
"Following a detailed family and personal history intake and physical exam, each woman on
their initial visit is categorised into low (standard), high, and indeterminate risk groups. Women
found to be at high risk of developing breast and/or ovarian cancer were referred for further
testing, additional screening measures, or participation in chemoprevention trials" states
Muggia.
Often women will not undergo screening procedures because of economic concerns, this
program however, is completely free.
Continued and sustained efforts are needed on all fronts (education, practice, and research,
policy) to improve the poor cancer-related outcomes for ethnic minorities.
Author:
Franco Muggia: Division of Medical Oncology, NYU Langone Cancer Institute, New York, NY
10016, USA.
ecancer is the online open-access peer-reviewed journal from the European Institute of
Oncology in Milan, Italy.
3 月 24 日
172
Relief For Cancer Treatment Side Effects Available For First
Time
Painful skin and nail conditions caused by chemotherapy and radiotherapy treatments can
now be treated thanks to the launch of an innovative range of cosmetics specifically developed
to enhance quality of life for cancer patients.
The Evolife product range, available exclusively from Feel Better Ltd, has been designed to
make unpleasant cutaneous side effects of chemo and radiotherapy treatments more bearable.
The collection includes gels, sprays and creams, and is already used by a number of leading
oncologists and cancer treatment centres in France, China, the Netherlands, Belgium and
Mexico, with remarkable results.
Evolife provides solutions to problems that previously had few answers. These include cracked
and broken nails (Evonail); flaking and broken skin (Evoskin); mouth ulcers (Evomucy), dry
mouth (Evodry) and body odour (Evodeo), to name but a few.
The range is currently only available in the UK and Republic and Ireland through Feel Better's
website: http://www.feelbetterduringchemo.com.
The active ingredient of the Evolife range is the 'Totum Lithium' formula, which aids the healing
process and in most cases actively reduces the pain and suffering caused by anti-cancer
therapies. Totum Lithium is naturally present in Evaux-les-Bains spring water where Evolife
Laboratories' cosmetics are manufactured. This French spring water has long been famed for
its regenerative and anti-inflammatory properties.
Derek Peddle, joint Managing Director of Feel Better Ltd says: "Most people know someone
who has gone through treatment for cancer but they may not realise how debilitating the side
effects can become. Mouth ulcers, excessive sweating, a constantly dry mouth and inflamed
hair roots aren't issues you want to tell everyone about.
"Cracked and broken nails can develop into an extremely painful condition that can even make
turning the page of a magazine unbearable. By calming these side effects, we hope to make a
real difference to the lives of those living through treatment - enabling them to be more positive
about their lives in some small way.
"These cosmetics can make a real difference. Side effects may seem minor but can be
debilitating and embarrassing. Cancer patients are often prepared to stop chemotherapy
treatment because they can't stand the pain of cracked nails and sores on their skin. Using
Evolife cosmetics can restore their confidence, enabling them to restart chemotherapy
knowing they can manage the side effects more effectively."
173
Charles Felgate, joint Managing Director of Feel Better Ltd, says: "We're proud to be bringing
the Evolife range of products to the UK and Ireland. Since its launch in France the reaction
from cancer patients and oncologists has been overwhelming, and early feedback here is
equally enthusiastic."
"To our knowledge, there is no other range of cosmetics that can improve the condition of
cutaneous side effects of people undergoing chemo and radiotherapy."
"Evolife cosmetics are designed to make cancer patients' lives more bearable, to give them
back some level of normality and create a huge psychological boost during a very stressful
time."
The Evolife range of products tackles side effects such as cracked and broken nails, cracked
and flakey skin, excessive sweating, dry mouth syndrome, acne, painful hair roots and ulcers
as well as offering a range of day-to-day general hygiene products.
To learn about the range of products and the accompanying scientific information, please visit
http://www.feelbetterduringchemo.com
Source
Feel Better Ltd
3 月 24 日
Needs Of Cancer Survivors Ingored By NHS, Say Nurses,
United Kingdom
Four out of five nurses (82 per cent) say the needs of people living with or after cancer in the
UK are not being met by the NHS, according to a new survey by Macmillan Cancer Support
and the Nursing Times.
Nurses report that following initial treatment, 92 per cent of patients experience physical
problems and 96 per cent experience emotional problems but they say these needs are not
properly addressed.
A lack of services available to help people adjust to the consequences of cancer and its
treatment, insufficient advice about returning to work and how to cope financially make it
difficult for patients to get their lives back on track after treatment, according to the nurses.
"It is shocking that so many nurses believe the NHS is failing cancer survivors. Two million
people are currently living with a cancer diagnosis and yet our survey shows not all nurses
have access to training or can find the services to help these people, many of whom are in
desperate need," said Jessica Corner, Chief Clinician at Macmillan Cancer Support.
174
Only two out of three (63 per cent) of the nurses who received training to help care for people
with a cancer diagnosis said it had given them adequate understanding and knowledge of the
needs of cancer survivors.
People living with and beyond cancer often have difficulty getting their lives back when hospital
treatment ends. They may experience emotional problems, side effects such as severe fatigue
or lymphoedema, or find it hard to get back to work, pay the bills or start a family.
Fran, 57, from London was diagnosed with cancer of the retina in 2006. She says: "Once my
treatment was over, I was abandoned. There was no system to support me, no one asked me
how I would cope emotionally, and when I started suffering side effects, I felt like I was making
a fuss about nothing. Even at work, I was made to feel like a nuisance and took early
retirement. I'm still lacking in energy and I experience flashing lights so do I still have cancer?
Has it been cured? Is it going to return? I have nobody to answer my questions. The absolute
silence of support is deafening."
A 15-page supplement addressing the long-term needs of cancer survivors will be included in
theNursing Times on 31 March 2009. The supplement includes information on the long-term
physical and emotional effects of cancer treatment, advice on how nurses can help their
patients return to a normal life and tips on caring for carers.
For
Macmillan's
latest
learning
and
development
opportunities
visit:
http://www.macmillan.org.uk/learnzone
1. The online survey was conducted on the <>website between 7January - 4 February 2009.
798 registered nurses, working in cancer and other disciplines, took part.
2. The results were as follows:
- 99% of nurses thought people who have experienced cancer face problems after treatment
- 82% said the needs of cancer patients are not being met
- In the nurses' experience, 96% of cancer patients suffer emotional problems following initial
treatment, 92% experience physical problems and 78% have money worries
- 38% of health professionals do not have access to specific education or training to support
people who have had a cancer diagnosis
- 72% of nurses say insufficient services available to help people adjust to the practical and
emotional after-effects of treatment are a major barrier to people getting their lives back after
treatment
175
- 60% thought inadequate assessment of people's physical, emotional and social needs was a
major barrier to people getting their lives back after treatment
- 60% thought a lack of information about returning to work or finances was a major barrier to
people getting their lives back after treatment
- 96% of nurses considered meeting the needs of carers to be part of their job
- 62% of nurses are aware of specific services for carers of people living with cancer.
- Only 63% of nurses who have received specific training/education to meet the needs of
people who have had a cancer diagnosis said that it was sufficient.
About Macmillan Cancer Support
Macmillan Cancer Support improves the lives of people affected by cancer, providing practical,
medical, emotional and financial support. Working alongside people affected by cancer,
Macmillan works to improve cancer care. One in three of us will get cancer. Two million of us
are living with it. If you are affected by cancer Macmillan can help.
Source
Macmillan Cancer Support
3 月 24 日
New Data On Cancer Survival In Europe Show More Patients
Are Cured
New data and analyses from a long-running study of cancer survival in Europe have shown
that the number of people actually cured of cancer - rather than just surviving for at least five
years after diagnosis - is rising steadily.
A special issue of the European Journal of Cancer [1] containing reports from the
EUROCARE-4 Working Group, includes, for the first time, an estimate of the proportions of
patients who are cured of their cancer in Europe and who, therefore, have a life expectancy
equal to that of the rest of the population. The analysis divides patients into two groups - the
proportion who may be considered cured of their disease and who are likely to die of
something else, and those who will die of their cancer.
The study compared two periods - 1988-1990 and 1997-1999 - and found the proportion of
patients estimated to be cured of lung, stomach and colorectal cancers increased from 6% to
8%, from 15% to 18% and from 42% to 49%, respectively.
Dr Riccardo Capocaccia of the National Centre for Epidemiology, Surveillance and Health
176
Promotion (Rome, Italy), who is the guest editor of the EUROCARE-4 special issue, said:
"Increases between 1988-1990 and 1997-1999 in the estimated proportion of European
patients cured of lung, stomach and colorectal cancers are noteworthy. The proportion cured is
not affected by 'lead time' (earlier diagnosis without improvement in life expectancy), so these
trends suggest genuine progress in cancer control."
However, as with many other papers in the EJC special issue, the paper on the proportion of
cured patients showed there were significant differences between countries in Europe.
For all cancers combined, most men (47%) were cured in Iceland and most women (59%)
were cured in France and Finland, while in Poland the least men (21%) and women (38%)
were cured.
Dr Capocaccia said: "For all cancers combined, the very wide range in the proportion of
patients cured in the contributing countries, ranging from 21% to 47% in men and 38% to 59%
in women, also depends on the varying frequency across Europe of the different cancers. This
proportion is, therefore, also an indicator of Europe-wide variations in cancer control, because
it reflects progress in diagnosis and treatment, as well as success in the prevention of the most
fatal cancers.
"Geographic variation in the estimated proportion of patients diagnosed in 1988-1999 who
were cured ranged from about 4% to 10% for lung cancer, from 9% to 27% for stomach cancer,
from 25% to 49% for colon and rectum cancer, and from 55% to 73% for breast cancer."
For instance, Denmark, Czech Republic and Poland had the lowest proportion of cured lung
cancer patients (less than 5%), while France and Spain had the highest (more than 10%). For
colorectal cancer, less than 30% were cured in Poland, Czech Republic and Slovenia but 49%
were cured in France. In Finland, France, Spain and Sweden, about 73% of breast cancer
patients were cured, while the proportion was less than 60% in Czech Republic, Poland and
Slovenia.
For prostate cancer, the proportion of men cured was associated more with the intensity of
PSA testing activity than with the efficacy of treatments. France led the way with more than
60% of men cured, while only 14% were cured in Denmark. This difference was largely due to
cases diagnosed earlier through the PSA test, and many of these prostate cancers would not
have killed and might not even have given rise to any symptoms. Indeed, prostate cancer
mortality was no higher in Denmark than elsewhere in Northern Europe.
For breast cancer, results showed a gap between Poland, the Czech Republic and Slovenia
and more western European countries of about 10%. "Part of this difference has been
attributed to the introduction of breast cancer screening from the mid-1990s in several western
European countries. If this is true, the implication is that early diagnosis saves the lives of
women with breast cancer by rendering their disease more curable," said Dr Capocaccia.
177
The EUROCARE study has been running since 1990 and is the widest epidemiological study
on the survival of cancer patients in Europe. This most recent report, EUROCARE-4, includes
data from 93 population-based cancer registries in 23 European countries, covering a total
population of about 151,400,000, which represents 35% of the total population in those
countries. The EUROCARE-4 database contains the anonymised records for more than
13,500,000 cancer patients diagnosed during the period 1978-2002, with information on their
vital status up to 31 December 2003 or later. Preliminary data on survival from EUROCARE-4
were published in 2007.
In addition to the estimates of the proportion of patients cured, data in the EJC special issue
that are new since 2007 include comparisons of survival between the elderly and the
middle-aged, between men and women and the survival of children.
Survival of the elderly (70-99 years) was lower than for middle-aged patients (55-69 years). Dr
Capocaccia said: "This is probably due to more advanced stage of disease at diagnosis, other
serious conditions, and more difficult access to, or lack of availability of, appropriate care. The
difference was particularly evident for women. During the period 1995-2002 covered by
EUROCARE-4, five-year survival improved less for patients aged 70-84 than for those aged
55-69, widening the gap in survival between these two age bands. Survival differences
between the oldest and middle-aged patients were mainly concentrated in the first year after
diagnosis: five-year survival conditional on survival for the first year after diagnosis varied
much less with age than unconditional five-year survival, suggesting that older patients are
often diagnosed too late to be efficiently treated."
Women have longer life expectancy than men and better survival from chronic diseases like
cardiovascular disease and cancer. Age-adjusted five-year relative survival was higher in
women than men for 21 out of 26 types of cancer for which survival was estimated in both
sexes. Particularly marked differences were found for cancers of the head and neck, bone,
thyroid and stomach, and for melanoma of the skin. Women had significantly lower survival
only for cancers of the biliary tract, bladder and larynx. For all cancers combined, and after
adjustment for age and for the different patterns of cancer in each sex, women had a two per
cent overall advantage in five-year survival (52% vs. 50%). The survival advantage for women
younger than 64 was four per cent; this difference decreased with increasing age, becoming
negligible in the elderly.
"This suggests that sex hormone patterns may play a role in the consistently higher survival
seen for women," said Dr Capocaccia.
In children, adolescents and young adults, five-year survival for all cancers combined was 81%
in children (0-14 years) and 87% in adolescents and young adults (15-24 years). From
1995-1999 to 2000-2002, the risk of death within five years of diagnosis fell significantly for
young patients, by 8% in children and 13% in adolescents and young adults. International
differences in survival also narrowed for children and young adults. Survival improved over
time for all the main cancer types affecting the young. The improvement was statistically
178
significant for acute lymphoid leukaemia and central nervous system tumours in children and
for non-Hodgkin lymphoma in adolescents and young adults.
"Cancer survival in patients aged less than 25 years is poorly documented in Eastern
European countries. Complete cancer registration should be a priority for these countries, as
an essential part of a policy for effective cancer control in Europe," said Dr Capocaccia.
Professor Alexander M.M. Eggermont, president of ECCO - the European CanCer
Organisation, welcomed the latest data from EUROCARE-4. "EUROCARE-4 provides
essential information on the pattern of survival of cancer patients across Europe. Without this
information it would be impossible to assess whether improvements in cancer diagnosis,
treatment and care are actually having an effect on the outcome for patients. It also tells us
what cancers and which areas of Europe need to be targeted for further research and
investment.
"The good news is that, for most cancers, survival has increased during the 1980s and 1990s.
There were big differences between countries; however, most of the largest increases in
survival have occurred in countries where survival was low at first, and this has contributed to
a reduction in the disparities in survival across Europe.
"Europe is changing, with more countries joining the EU, and cancer medicine is also changing
and improving. This means that more people have higher expectations of the medical
profession. We must do our best to meet these expectations and help both patients and
colleagues by disseminating information about better diagnostics, treatments and cures as
widely as possible across the whole of Europe, and, indeed, the world. This will be achieved by
collaboration and communication, and future EUROCARE studies will, no doubt, chart how
successful we have been. Cancer registries play a vital role here, and I would urge all
countries to protect and develop them so that information on cancer incidence and survival
becomes ever more accurate."
Notes:
[1] European Journal of Cancer, Vol 45, issue 6 (April 2009), pages 901-1094. "Survival of
cancer patients in Europe, 1995-2002: The EUROCARE 4 Study."
The European Journal of Cancer is the official journal of ECCO - the European CanCer
Organisation.
ECCO - the European CanCer Organisation - exists to uphold the right of all European cancer
patients to the best possible treatment and care and to promote interaction between all
organisations involved in cancer research, education, treatment and care at the European
level.
3 月 25 日
Pilgrims' progress: Genetic data from 1630s backs health
179
benefits of cancer screening
SALT LAKE CITY, March 25, 2009 – In the 1630s, the Fry family came to the New World with
more than just dreams of prosperity and freedom — they also came with a genetic mutation
that increased the likelihood of colon cancer in hundreds, if not thousands, of their
descendants. The scientists who traced that gene back almost 370 years are now reporting
that routine screening and education can prevent people with the mutated gene from
developing cancer.
Their new report on Mr. and Mrs. George Fry, who likely arrived in Massachusetts colony
aboard the William & Mary, was presented today at the 237th National Meeting of the
American Chemical Society (ACS).
Deb Neklason, Ph.D., and colleagues explained how they used cancer records and a massive
genealogic archive known as the Utah Population Database (UPDB) to trace the genetic
condition to a Utah pioneer family and their 7,000 descendents. A New York family with the
same genetic condition was also linked to the Utah group, which helped trace the two families
back 16 generations to the Frys. The gene mutation causes a condition known as attenuated
familial adenomatous polyposis (AFAP). AFAP causes the growth of colorectal polyps that
have the potential to become cancerous.
People with the AFAP mutation have about a two in three risk of getting colon cancer,
compared to about one in 24 for the general population. Once aware they have inherited the
gene, these individuals usually follow a regimen of periodic screening for the polyps with
colonoscopy, and removal of suspicious growths, in an effort to avoid cancer.
Neklason described how the findings have already helped living relatives of the Frys avoid
colon cancer. Their genetic detective work enabled the researchers to identify individuals at
risk and notify them.
"Our work demonstrates that colon cancer can be prevented with proper screening and care.
Aggressive education and clinical intervention over a seven-year window in the Utah family
has already prevented seven colon cancers," says Neklason.
Through molecular testing, Neklason was able to find 15 families with the identical genetic
change who appeared to be related. According to Neklason, this might be just the tip of the
iceberg. She suggests that there may be thousands more people at risk from inheriting the
mutated gene.
Colon cancer is the third most common cancer in the United States, with more than 150,000
cases diagnosed in the United States each year. Most cases do not result from any known
inherited mutations. For those carrying the AFAP mutation, a higher susceptibility to polyps
means early diagnosis could be difference between life and death.
180
"It could have an impact on a lot of people out there. We ran some numbers and if this
mutation accounted for just 0.1 percent of all of the colon cancers in the U.S. that would equal
150 cases a year and cost about $7.5 million per year to treat," says Neklason. "And that's a
conservative estimate."
The researchers studied approximately 200 of the Frys' descendants with the genetic
mutation from two different families in Utah and New York State, identifying genetic and
lifestyle differences that increased the likelihood of polyps. The group identified a gene known
as NAT1 that may influence polyp growth.
Using an extensive diet questionnaire, they also found that a high fat diet and obesity lends
itself to more polyps. On the other hand, fish fats, bananas, calcium, aspirin and caffeine
demonstrated some protective effects. Neklason suggests that this information extends to
general colon cancer risk.
The newest aspect of the University of Utah's team's work is a chemoprevention study that
could make polyps shrink or recede entirely. She says the next step is to find out how many
more people have the AFAP mutation and help them prevent colon cancer.
"One of the big things we're trying to do is figure out how common this mutation is in the
United States. It's a public health issue… It's really powerful to know that information," says
Neklason.
###
The American Chemical Society is a nonprofit organization chartered by the U.S. Congress.
With more than 154,000 members, ACS is the world's largest scientific society and a global
leader in providing access to chemistry-related research through its multiple databases,
peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C.,
and Columbus, Ohio.
3 月 26 日
Data suggesting that omacetaxine can eradicate leukemic
stem cells may offer a breakthrough for CML
Drug showed 90 percent kill of leukemic stem cells and prolonged survival in mice
with resistant CML
MELBOURNE, Australia, and MENLO PARK, California U.S.A. (March 26th, 2009)
– Data showing the ability of omacetaxine to kill leukemic stem cells
in mouse models with drug-resistant chronic myelogenous leukemia (CML)
are the subject of an advance online publication in the journal Leukemia,
181
ChemGenex Pharmaceuticals Limited (ASX:CXS and NASDAQ:CXSP) announced
today. The findings of this study provide new insights into the problem
of minimal residual disease and may open the door to the development of
a curative treatment strategy for some patients with CML.
Commenting on the publication, Dr. Shaoguang Li, the study leader at the
University of Massachusetts Medical School, said, "Omacetaxine killed 90%
of the leukemic stem cells in vitro. In contrast, imatinib and dasatinib,
the two leading CML drugs, only controlled 9% and 25% of these cancer stem
cells, respectively. We further demonstrated that omacetaxine prolonged
survival in test animals carrying the T315I mutation, which would normally
render them resistant to all currently available drugs."
ChemGenex is currently developing omacetaxine as a potential treatment
for a range of blood malignancies, including CML, and is completing a
pivotal study in CML patients who harbor the T315I mutation. The company
expects to complete its filing of a New Drug Application for use of
omacetaxine in that patient population to the U.S. Food and Drug
Administration by mid-year.
In the USA, almost 5,000 new cases of CML are diagnosed each year and recent
estimates suggest that by 2025, prevalence will be 300,000. While there
are a number of licensed drugs, collectively known as tyrosine kinase
inhibitors (TKIs), which are very effective in treating CML, they must
be administered daily for the rest of the patient's life; very few patients
remain disease free when these drugs are discontinued.
Hagop M. Kantarjian, M.D., Chairman and Professor, Department of Leukemia,
at M.D. Anderson Cancer Center in Houston, Texas, described the study
results as "very promising". He added, "While the currently licensed drugs
target and disable the diseased cells in the blood stream and bone marrow,
they have little, if any, affect on the primitive leukemic stem cells that
are at the "root" of this blood cancer. I look forward to working with
ChemGenex in future trials to evaluate the clinical application of these
recent findings. "
Greg Collier, Ph.D., Managing Director and Chief Executive Officer of
ChemGenex added, "The results of Dr. Li's animal study are very
encouraging and we are currently collaborating with Professor Tessa
Holyoake from the United Kingdom, to carry out similar investigations in
primary human stem and progenitor cells. In the meantime, ChemGenex
remains focused on our primary objective of developing omacetaxine as a
therapeutic option for CML patients who have developed the T315I mutation
and who are resistant to all first and second line TKIs. This is the most
pressing unmet medical need in the field of CML management."
182
###
About CML
CML is a form of leukemia characterized by the increased and unregulated
growth of undifferentiated myeloid cells in the bone marrow and the
accumulation of these non-functional cells in the blood. Healthy myeloid
cells should give rise to some of the most important components of blood:

red cells (to carry oxygen around the body), platelets (to help with blood clotting) and
certain white cells (to help defend against infection).
CML patients therefore show symptoms of anemia and are prone to bleeding
and are susceptible to illnesses caused by bacterial and fungal
infections.
Minimal residual disease (MRD) is the name given, to small numbers of
leukemic cells that remain in the patient during treatment, or after
treatment when the patient is in remission (no symptoms or signs of
disease). It is the major cause of relapse in cancer and leukemia.
About Omacetaxine
Omacetaxine mepesuccinate is a first-in-class cetaxine with demonstrated
clinical activity as a single agent in a range of hematological
malignancies. Omacetaxine has a novel mechanism of action, and induces
apoptosis by inhibition of protein synthesis, particularly Mcl-1. As
omacetaxine acts independently of tyrosine kinase inhibitors, it may have
a therapeutic advantage for patients who have developed resistance to TKIs.
Omacetaxine is administered subcutaneously.
About ChemGenex Pharmaceuticals Limited (http://www.chemgenex.com)
ChemGenex Pharmaceuticals is a pharmaceutical development company
dedicated to improving the lives of patients by developing personalized
oncology medicines. ChemGenex harnesses the power of genomics both to
discover novel targets and drug compounds, and in clinical trials to
develop more individualized treatment outcomes. ChemGenex's lead
compound, omacetaxine mepesuccinate, is currently in phase 2/3 clinical
trials for chronic myeloid leukemia (CML). ChemGenex has a second
anticancer compound, amonafide dihydrochloride (Quinamed®) which is in
phase 2 clinical development for various solid cancers, and a portfolio
of assets in pre-clinical development. ChemGenex currently trades on the
Australian Stock Exchange under the symbol "CXS" and on NASDAQ under the
183
symbol "CXSP". For additional information on ChemGenex Pharmaceuticals,
please visit our web site at http://www.chemgenex.com.
Details on the clinical trials can be accessed from the following websites;
http://clinicaltrials.gov/ct2/show/NCT00375219?term=homoharringtonine
&rank=9 and http://www.tkiresistantcmltrials.com
Contacts
ChemGenex Information
Dr. Greg Collier
CEO and Managing Director
Cell (Australia): +61 419 897 501
Cell (USA): +1 650 200 8145
Email: gcollier@chemgenex.com
Media Relations – USA
Joan Kureczka
Kureczka/Martin Associates
Tel: +1 415 821 2413
Email: Jkureczka@comcast.net
Media Relations – Australia
Rebecca Wilson
Buchan Consulting
Tel: +61 2 9237 2800
Cell: + 61 (0) 417 382 391
Email: rwilson@bcg.com.au
Safe Harbor Statement
Certain statements made herein (including for this purpose sites to which
a hyperlink has been provided) that use the words "estimate", "project",
"intend", "expect", "believe" and similar expressions are intended to
identify forward-looking statements within the meaning of the US Private
Securities Litigation Reform Act of 1995. These forward-looking
statements involve known and unknown risks and uncertainties which could
cause the actual results, performance or achievements of the company to
be materially different from those which may be expressed or implied by
such statements, including, among others, risks or uncertainties
associated with the development of the company's technology, the ability
to successfully market products in the clinical pipeline, the ability to
advance promising therapeutics through clinical trials, the ability to
establish our fully integrated technologies, the ability to enter into
additional collaborations and strategic alliances and expand current
184
collaborations and obtain milestone payments, the suitability of
internally discovered genes for drug development, the ability of the
company to meet its financial requirements, the ability of the company
to protect its proprietary technology, potential limitations on the
company's technology, the market for the company's products, government
regulation in Australia and the United States, changes in tax and other
laws, changes in competition and the loss of key personnel. These
statements are based on our management's current expectations and are
subject to a number of uncertainties that could change the results
described in the forward-looking statements. Investors should be aware
that there are no assurances that results will not differ from those
projected.
3 月 26 日
New way to make stem cells avoids risk of cancer
A team of scientists has advanced stem cell research by finding a way to endow human skin
cells with embryonic stem cell-like properties without inserting potentially problematic new
genes into their DNA. The team was led by James A. Thomson, V.M.D., Ph.D., of the
University of Wisconsin-Madison and supported in part by the National Institute of General
Medical Sciences, a component of the National Institutes of Health.
This is not the first time that scientists have endowed differentiated cells like skin cells with
the capacity to develop into any of the roughly 220 types of cells in the body, a process known
as induced pluripotency. But it is the first time that they have done so without using viruses,
which can insert potentially harmful genes into the cells' genetic material and trigger cancer.
Thomson's new method imports the necessary genes on a small circle of DNA known as a
plasmid. Over time, the plasmid disappears naturally from the cell population, avoiding the
danger posed by using viruses.
Scientists view pluripotent cells as invaluable to studies of normal and disease processes and
to understanding the effects of certain drugs. In the future, doctors might be able to use such
cells therapeutically to replace those affected by diseases such as Alzheimer's and
Parkinson's or lost to traumatic injuries.
###
In addition to NIGMS, NIH's National Center for Research Resources also supported this study
through a resource grant.
ARTICLE: "Human Induced Pluripotent Stem Cells Free of Vector and Transgene Sequences"
by Junying Yu, Kejin Hu, Kim Smuga-Otto, Shulan Tian, Ron Stewart, Igor I. Slukvin and
185
James A. Thomson. The paper will appear online in Science Express on Thursday, March 26,
2009.
SPOKESPEOPLE: Available to comment on this work and its importance to the field of stem
cell biology are NIGMS Director Jeremy M. Berg, Ph.D., as well Marion Zatz, Ph.D., and Susan
Haynes, Ph.D., who oversee NIGMS stem cell grants.
CONTACT: To schedule an interview, contact the NIGMS Office of Communications and Public
Liaison at 301-496-7301 or info@nigms.nih.gov.
NIGMS is a part of NIH that supports basic research to increase our understanding of life
processes and lay the foundation for advances in disease diagnosis, treatment, and
prevention. For more information on the Institute's research and training programs, see
http://www.nigms.nih.gov.
The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes
27 Institutes and Centers and is a component of the U.S. Department of Health and Human
Services. It is the primary Federal agency for conducting and supporting basic, clinical, and
translational medical research, and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and its programs, visit
www.nih.gov.
Download a high-resolution version of this illustration from the NIGMS Image Gallery at
http://images.nigms.nih.gov/index.cfm?event=viewDetail&imageID=1294.
3 月 26 日
Ezetimibe And Ezetimibe/Simvastatin Combo Pose No
Increased Cancer Risk, Study Shows
A new study shows no increased cancer risk with ezetimibe mono and ezetimibe/simvastatin
combination treatments, compared to cancer rates of other powerful lipid-lowering statin
therapies. The study, conducted by Tufts Medical Center lipid and health policy experts, was
published in the April issue of the Journal of Clinical Lipidology (http://www.lipidjournal.com).
"This real-world examination shows no increased risk to patients taking ezetimibe alone or the
ezetimibe/simvastatin combination to lower their lipid levels -- an issue that sparked many
policy and health safety conversations," said lipidologist Richard Karas, MD, PhD, Professor of
Medicine, Tufts University School of Medicine and Associate Director, Molecular Cardiology
Research Institute, Tufts Medical Center, who co-authored the study along with Tufts Medical
Center colleague, Alawi A. Alsheikh-Ali, MD, Institute for Clinical Research and Health Policy
Studies.
186
Researchers at Tufts Medical Center and Tufts University School of Medicine studied rates of
reports of cancer as an adverse event filed with the U.S. Food and Drug and Administration
(FDA) for patients taking ezetimibe or ezetimibe/simvastatin compared to patients on
mono-therapy with simvastatin, atorvastatin or rosuvastatin, during a four-year period. This is
the first study to use the FDA database to evaluate potential cancer risk of cholesterol-lowering
medications.
The Tufts researchers found 2,334 cases of cancers reported in the total population studied.
Cancer rates were analyzed accounting for the number of prescriptions for each treatment
dispensed across the country, based on a total of 559 million prescriptions for all of the
cholesterol-lowering medications evaluated. The analysis found cancer reported in 2.9 per
million prescriptions for ezetimibe, 1.3 per million prescriptions for ezetimibe/simvastatin
therapy and an average of 4.1 per million prescriptions for other lipid lowering treatment.
These rates demonstrate no increase in cancer for ezetimibe and ezetimibe/simvastatin
regimen versus the other treatments studied.
"These data will hopefully return the conversation between physicians and patients back
toward the most pressing public health risk in America -- unmanaged high LDL that can result
in heart disease or stroke -- the nation's number one and number three killers," continued Dr.
Karas.
This research, which explored three times more cancers than analyzed by Sir Richard Peto
from the SEAS, SHARP and IMPROVE-IT studies published in the New England Journal of
Medicine, September 2, 2008, is consistent with Peto's final report supporting no credible
evidence that ezetimibe or ezetimibe/simvastatin increase the risk of developing cancer.
Funding Sources and Disclosures
No specific corporate funding was requested or obtained for data collection, analysis and
publication of these findings. Dr. Karas has received speaker's fees and/or consulting fees
from Merck, Abbott, and Schering-Plough. Dr. Alsheikh-Ali is a recipient of a faculty
development award from Pfizer/Tufts Medical Center.
Tufts Medical Center
3 月 26 日
Paradox Of Cancer Drugs Gives Clue To Why Some Treatments
Fail
Cancer Research UK funded scientists have found that some types of cancer drugs called
angiogenesis inhibitors can encourage tumour growth rather than stunt it - according to
research published in Nature Medicine * .
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These drugs are designed to block the supply of blood to the tumour to prevent it from growing.
This research focused on an experimental angiogenesis inhibitor called cilengitide that has not
yet been licensed for patients.
The scientists based at The Institute of Cancer, Queen Mary, University of London **, the
Institute of Cancer Research (ICR) and the Beatson Institute for Cancer Research found
evidence to suggest that low doses of cilengitide in laboratory studies can have the opposite
effect to what was expected and promote cancer growth***.
Study author, Dr Andy Reynolds, from the Breakthrough Breast Cancer Research Centre at
the ICR, said: "Our study revealed a previously unknown mechanism through which drugs
such as cilengitide behave. It showed that while higher concentrations of cilengitide can block
angiogenesis, lower concentrations can actually stimulate the supply of blood to the tumour
and can promote its growth. These results may explain why initial results from early stage
clinical trials have not been as promising as hoped.
"Knowledge of this mechanism will help us develop new ways to make these drugs as effective
as possible. In the future, we may be able to combine these inhibitors with other drugs to
maximise their effectiveness for patients."
Dr Lesley Walker, director of cancer information at Cancer Research UK said: "Drugs redirect
the body's complex signalling systems. Sometimes very subtle alterations to the way a drug is
administered, or subtle changes to a drug's structure, can have a huge impact on its
effectiveness.
"This study is important because it may help to explain the mixed results previously seen in
patients and turn around disappointing results so people may still benefit from the drug without
the potential harm."
"Other anti-angiogenesis drugs like sunitinib (Sutent) and bevacizumab (Avastin) have proven
effective enough for use in the NHS but there is still need to understand why they can
sometime fail. It may be that there are similar mechanisms at work."
To listen to an interview with Dr Andy Reynolds click here.
Notes
*Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin
inhibitors. A Reynolds et al. Nature Medicine. March 2009.
**The study was led by Dr. Kairbaan Hodivala-Dilke based at The Institute of Cancer, Queen
Mary, University of London.
***The scientists showed through laboratory studies that angiogenesis inhibitors which target
188
integrins can alter the way in which integrins and VEGF receptors move inside blood vessels.
By altering the movement of integrin and VEGF receptors inside the blood vessel, they
promote cell movement and angiogenesis.
This study coincides with the publication of other lab-based research published in the journal
Cancer Cell this month showing that other types of angiogenesis inhibitors already on the
market, such as sunitinib (Sutent), can sometimes encourage tumour growth rather than stunt
it. It is possible these findings might help to explain why this can happen although this study
did not seek to do that. These papers are:
Accelerated Metastasis after Short-Term Treatment with a Potent Inhibitor of Tumor
Angiogenesis. Cancer Cell. John M.L. Ebos. DOI 10.1016/j.ccr.2009.01.021
And Antiangiogenic Therapy Elicits Malignant Progression of Tumors to Increased Local
Invasion
and
Distant
Metastasis.
Cancer
Cell.
Marta
Pa`
ez-Ribes.
DOI
10.1016/j.ccr.2009.01.027
Source
Cancer Research UK
View drug information on Avastin; Sutent.
3 月 26 日
New Cancer Centre Launched In Northern Ireland
Belfast yesterday joins a unique chain of Cancer Research UK Centres that are being
launched across the UK.
These cancer centres will draw together world class research and areas of medical expertise
to provide the best possible results for cancer patients nationwide.
As one of the first centres, the Belfast Cancer Research UK Centre will help set the pace for
national and international progress in cancer of the bowel cancer, oesophagus and breast
cancer. It will also concentrate on pioneering the latest techniques in radiotherapy, improving
cancer diagnosis and developing new, more effective drugs.
Collaboration is the key to the success of the Centre which will focus on identifying new targets
for cancer drugs, understanding how genes can help predict which treatment will be most
effective and developing specific new treatments that have fewer side effects.
Cancer Research UK already supports research in Northern Ireland but is looking to increase
its contribution up to £2.5m a year to help develop the Centre.
189
Professor Patrick Johnston, Dean of Medicine, Dentisty and Biomedical Sciences and Chair of
the board of the new centre, said: "This is a very exciting development for cancer care and
cancer research in Northern Ireland. It will add greatly to the options available for cancer
patients and is recognition of the quality of cancer care and cancer research already taking
place at Queen's University Belfast and the Belfast Trust."
The Centre aims to be a world leader in developing treatments tailored to individual cancer
patients based on understanding the biology of the disease and how that varies among
patients. It brings together the researchers and support from Queen's University Belfast,
Northern Ireland's Health & Social Care Research & Development Office, Cancer Research
UK and Belfast Health and Social Care Trust.
Allister Murphy, 52, has first hand experience of taking part in cancer research after being
diagnosed with prostate cancer in February 2008. Following a routine visit to his GP a biopsy,
MRI and bone scan confirmed that the cancer had spread to his spine, ribs and pelvis.
Hormone treatment was recommended.
Allister was offered the opportunity to take part in a clinical trial that was researching an
improved, more tailored treatment for advanced prostate cancer. His doctor will be involved in
research at the new centre.
"Taking part in this clinical trial means that while my present medication is working, Dr.
O'Sullivan and his team are investigating whether a combination of drugs in addition to
hormone treatment would be more effective," said Allister, "and this gives hope for the future not just for me, but others."
Allister - an IT consultant - is very proud of the fact that he has had no days off work in the last
34 years and that he has been able to maintain a very positive attitude to his illness. Although
still receiving treatment Allister is living life to the full and is currently in training for the Belfast
Marathon.
Professor Dennis McCance, who is director of the Centre for Cancer Research and Cell
Biology at Queen's University and on the Centre's board, said: "This exciting new initiative will
bolster our efforts to bring together a variety of researchers and clinicians to collaborate and
work together to improve the lives of cancer patients across Northern Ireland. By building
closer links between scientists and doctors we want to increase the pace of research, leading
to improved treatments for patients."
"Northern Ireland is the third link in this exciting chain of cancer centres. We should rightly be
proud of the part we're playing in moving the latest scientific discoveries from the laboratory to
the patient's bedside. We'll be focusing our efforts on better diagnosis and developing new
personalised treatments for patients which will include better and more effective drugs and
improving radiotherapy."
190
Professor Bernie Hannigan, Director of Research and Development for Health & Social Care,
Northern Ireland said: "Cancer research must be of the highest quality if it is to lead to better
diagnosis, treatment and care of patients and to the prevention of cancer. Quality is achieved
only when very costly resources are available to excellent clinicians and researchers.
"As a significant, long-term funder of cancer research in Belfast we are delighted with the
establishment of the Cancer Research UK Centre. We look forward to great achievements as
we work together for the benefit of Northern Ireland's people."
Harpal Kumar, chief executive of Cancer Research UK, said: "Funding these centres of
excellence is one of the charity's priorities and will enable us to work towards the goals we
have set to improve the treatment and survival of cancer patients. But we continue to welcome
the generous donations we receive from the public to ensure we can continue to build on what
we have started today."
Cancer Research UK plans to launch more centres around the UK during 2009.
Click here for more information about the new centre.
Latest figures show that around 7,000 cancer cases are diagnosed in Northern Ireland each
year.
More than 3,700 people die from cancer in Northern Ireland every year.
Cancer Research UK Centres aim to establish a nationwide network of excellence that will
provide the best possible outcomes for patients by linking research activity with patient care
and public engagement. Each Centre will focus on specific areas of research and aim to raise
standards of care and forge links with local communities.
The Centre for Cancer Research and Cell Biology (CCRCB), opened in 2007, will be the hub
of the Cancer Research UK Centre in Belfast. The Cancer Research UK Centre will provide
the resources to improve the link between the CCRCB and cancer services in Belfast for the
benefit of cancer patients.
Source
Cancer Research UK
3 月 26 日
Phase III Development Of ASA404 In Lung Cancer Extended
To Japan
Antisoma plc (LSE: ASM; USOTC:ATSMY) announces that ATTRACT-1, the Novartis phase III
trial evaluating ASA404 as a first-line treatment for non-small cell lung cancer, is now enrolling
191
patients in Japan. ATTRACT-1 has been enrolling patients in a variety of other countries since
it began in April 2008. Extension of the trial to Japan follows the successful completion of a
phase I study evaluating the safety of ASA404 in Japanese lung cancer patients.
Glyn Edwards, Antisoma's CEO, said "We're pleased that Japanese lung cancer patients can
now participate in this key phase III trial of ASA404. This is an important step towards a
potential application to market the drug in Japan."
The Trout Group
Except for the historical information presented, certain matters discussed in this statement are
forward looking statements that are subject to a number of risks and uncertainties that could
cause actual results to differ materially from results, performance or achievements expressed
or implied by such statements. These risks and uncertainties may be associated with product
discovery and development, including statements regarding the company's clinical
development programmes, the expected timing of clinical trials and regulatory filings. Such
statements are based on management's current expectations, but actual results may differ
materially.
About NSCLC
Lung cancer is the number one cause of cancer death for both men and women worldwide,
with 1.2 million new cases per year and 921,000 deaths. Around 85-90% of all lung cancer
cases are NSCLC. In Japan, there are approximately 66,000 new cases and 56,000 deaths
per year from lung cancer.
About ASA404
ASA404 (DMXAA) is a small-molecule Tumour-Vascular Disrupting Agent (Tumour-VDA)
which selectively disrupts tumour blood vessels, generating tumour death (necrosis) due to the
resulting lack of blood flow in the tumour. The drug was discovered by Professors Bruce
Baguley and William Denny and their teams at the Auckland Cancer Society Research Centre,
University of Auckland, New Zealand. It was in-licensed by Antisoma from Cancer Research
Ventures
Limited
(now
Cancer
Research
Technology),
the
development
and
commercialisation company of the Cancer Research Campaign (now Cancer Research UK), in
August 2001. In a randomised phase II study in non-small cell lung cancer (NSCLC), addition
of ASA404 to standard first-line chemotherapy was associated with a five month improvement
in median survival. Worldwide rights to ASA404 were licensed to Novartis AG in April 2007. In
addition to the ATTRACT-1 phase III trial testing ASA404 as a first-line treatment for NSCLC,
Novartis is conducting a phase III trial of ASA404 as a second-line treatment for NSCLC and
plans to evaluate the drug in patients with metastatic breast cancer.
About Antisoma
192
Antisoma is a London Stock Exchange-listed biopharmaceutical company that develops novel
products for the treatment of cancer. The Company has operations in the UK and the US.
Please visit http://www.antisoma.com for further information about Antisoma.
Source
Antisoma
3 月 26 日
Final NICE Kidney Cancer Guidance Recommends Sutent(R)
(sunitinib) Only, UK
The National Institute for Health and Clinical Excellence (NICE) has issued final guidance
recommending the use of Sutent (sunitinib) for the first-line treatment of metastatic renal cell
carcinoma (mRCC), commonly known as advanced kidney cancer.1 Sunitinib, the only oral
treatment to show overall survival greater than two years in advanced kidney cancer patients,
is one of four treatments which have been reviewed by NICE as part of a multiple technology
appraisal. This decision reverses NICE's earlier appraisal consultation document (ACD) issued
in August 2008, which advised against the use of all four medicines for the treatment of mRCC.
However, at a subsequent meeting of the appraisal committee, NICE took the decision to split
the appraisal process, resulting in firstly, a recommendation for sunitinib and secondly a
reappraisal of the other three treatments.
"I am delighted that Sutent will be available." said Professor Robert Hawkins, Christie Hospital
Manchester. "It will remove a great deal of anxiety and uncertainty for people diagnosed with
renal cancer to know that modern, effective treatment is now available to them" he continued.
The appraisal committee recognised that sunitinib provides a step-change in the first-line
treatment of advanced kidney cancer and has noted that more than 20% of the public and
patients that responded in consultation highlighted the impressive benefit from sunitinib 2 New
data for sunitinib have emerged since NICE began this appraisal process. Median overall
survival for patients who received sunitinib vs interferon-alpha (IFN-α) was 26.4 months vs.
21.8 months respectively (p=0.051). However, an exploratory analysis of patients who
received only one line of treatment (i.e. no subsequent treatments after stopping their sunitinib
or IFN-α therapies) showed that sunitinib almost doubles the time it keeps patients alive
compared to IFN-α [28.1 months vs 14.1, HR = 0.647 (p=0.0033, log-rank]). This is a reflection
of clinical practice in the UK where generally patients are only funded for one line of treatment
at most.3
It is estimated more than 7,000 people are diagnosed with kidney cancer in the UK each year
and approximately 3,600 people die from the disease.4 Until recently, treatment options were
limited to IFN-α, the current NHS funded standard of care.5 James Whale, Chairman of the
James Whale Fund for Kidney Cancer, expressed his delight on hearing the news, "Finally, we
have justice for the kidney cancer community. This positive recommendation from NICE will
193
allow thousands of kidney cancer patients in England and Wales access to this life-extending
treatment. The options previously available to us have been limited and are inadequate for the
majority of patients. For some, sunitinib is the only hope."
Currently, over half of PCTs (primary care trusts) in England are already funding sunitinib to
some extent for the treatment of mRCC. Across Western Europe eligible patients with
advanced kidney cancer are routinely prescribed sunitinib, where it is now recognised as a
standard of care.6
Pat Hanlon, spokesperson for Kidney Cancer UK commented "After two and half years of
campaigning we are delighted with this news and hope that PCTs will move quickly to
implement the NICE guidance and ensure these deserving and distressed patients get access
to a treatment that will allow them the chance of precious extra life."
Rob Day, Director of Oncology UK, Pfizer Limited, commented, "We are truly delighted that
NICE has taken the decision in its final guidance to enable UK patients to benefit from sunitinib,
a medicine that has become a standard of care in the rest of the world. Not only will this
decision have immediate benefits for eligible patients today, but will also pave the way for
future treatment advances in kidney cancer. "
Sunitinib, an oral medicine, received marketing authorisation in July 2006 and was approved
as a first-line treatment for mRCC in January 2007. It is a novel addition to a new class of
'multitargeted' anti-cancer drugs. It targets the tumour with a dual action approach, by stopping
the cancer cells from multiplying and also cutting off the tumour's blood supply.
Sunitnib for the treatment of GIST
Sunitinib is also indicated for the treatment of unresectable and/or metastatic malignant
gastrointestinal stromal tumour (GIST) after failure of imatinib mesylate. Updated results from
the sunitinib phase III study in GIST patients who failed on imatinib therapy showed a greater
than fourfold increase in time to progression (TTP) in sunitinib patients (27.3 weeks) compared
with those treated with placebo (6.4 weeks). Sunitinib treatment yielded significant
improvement in survival rates versus placebo at three and six months although with 88% of
patients in the placebo arm ultimately crossing over to sunitinib, the overall survival was similar
between groups.7
Sunitinib is licensed for the first and second line treatment of mRCC and the second-line
treatment of GIST. Sunitinib is currently undergoing an appraisal by NICE for the second-line
treatment of GIST. In 2007, Pfizer cut the price of sunitinib by five per cent and committed to
providing one cycle/course of the treatment free of charge to every eligible patient in the UK, in
an effort to increase patient access. This move amounts to an average saving of between 19
per cent and 29 per cent per patient for the cost of treatment, depending upon the type and
stage of their tumour.
194
One six-week cycle of sunitinib costs £3,138.80 (28 tablets of 50mg) in the UK. The average
annual cost in the UK for a patient taking sunitinib is £24,168 (this price includes one free
treatment cycle).
About Sunitinib
Sunitinib is a novel, oral, multi-targeted cancer therapy that selectively targets multiple
receptor tyrosine kinases (RTKs) involved in tumour growth, angiogenesis and the progression
of cancer. By inhibiting these RTKs, sunitinib targets multiple signaling pathways resulting in a
dual action anti-proliferative and anti-angiogenic effect, which may lead to tumour regression
and disease stabilisation.
The recommended starting dose for sunitinib is 50mg once daily for four weeks followed by
two weeks off. The dose can be modified in 12.5mg increments not to exceed 75mg or
decrease below 25mg. Sunitinib is available in 12.5 mg, 25mg, and 50mg capsules. Please
refer to the Summary of Product Characteristics (SPC) for additional dosing recommendations
regarding co-administration with cytochrome 3A4 inducers or inhibitors.
Adverse events (AEs) were generally mild to moderate. Most adverse events were reversible,
and generally did not result in discontinuation. In clinical trials, the most common treatment
related adverse events (>20%) included fatigue; gastrointestinal disorders, such as diarrhoea,
nausea, stomatitis, dyspepsia, and vomiting; skin discolouration; dysgeusia (loss of taste); and
anorexia. Fatigue, hypertension and neutropenia were the most common grade 3 treatment
related adverse events. Increased lipase (2%) was the most common grade 4 treatment
related adverse event. Hepatitis and hepatic failure occurred in <1% of patients and prolonged
QT interval events occurred in less than 0.1%.
The most important treatment related serious adverse events associated with sunitinib
treatment of solid tumour patients were pulmonary embolism (1%), thrombocytopoenia (1%),
tumor haemorrhage (0.9%), febrile neutropoenia (0.4%), and hypertension (0.4%). Developed
by Pfizer, sunitinib is being studied alone and in combination with other medicines as a
potential treatment for a number of other solid tumours, including breast, lung, prostate, and
colorectal cancers.
About Pfizer
Pfizer Inc, the world's largest research-based pharmaceutical company, discovers, develops,
manufactures and markets prescription medicines in 11 therapeutic areas including oncology,
cardiovascular, pain, neuroscience and infectious diseases, including HIV/AIDS. Pfizer is also
the world's largest animal health company. Pfizer Inc employs approximately 90,000
colleagues worldwide, all of whom are devoted to working for a healthier world. Pfizer
conducts more biomedical research than any other organisation, and has 12,000 professionals
working in six major R&D sites worldwide, including Sandwich in Kent. Pfizer's annual UK R&D
investment is more than £550 million - more than £10 million a week.
195
In the UK, Pfizer has its European R&D headquarters at Sandwich and its UK business
headquarters in Surrey, and is the major supplier of medicines to the NHS.
About Pfizer Oncology
Pfizer Oncology is committed to advancing the scientific understanding of cancer and to
bringing new medicines to address unmet medical needs in cancer patients. Oncology is a
research priority for Pfizer, with over 12 percent of the company's research and development
investment devoted to discovering and developing innovative therapies for treating breast,
colorectal and other cancers.
References
1 The National Institute for Health and Clinical Excellence http://www.nice.org.uk Accessed
March 2009
2 Sunitinib for the first-line treatment of advanced and/or metastatic renal cell carcinoma:
http://www.nice.org.uk/nicemedia/pdf/RenalCellCarcinomaFADFeb09.pdf Accessed February
2009
3 Figlin RA et al. Overall survival with Sunitinib versus Interferon-alfa (IFN-) as First-line
Treatment of Metastatic Renal Cell Carcinoma (mRCC), Abstract 5024 presented at ASCO
2008
4 Cancer Research UK. Available here. Accessed 14 May 2008.
5 Motzer RJ et al. Activity of SU11248, a multitargeted inhibitor or vascular endothelial growth
factor receptor and platelet-derived growth factor receptor in patients with metastatic renal cell
carcinoma. Journal of Clinical Oncology Jan 06 24:16-24
6 Ljungberg B, Hanbury D.C, Kuczyk A.S, et al. Guidelines on Renal Cell Carcinoma.
European Association of Urology 2007 (Page 22)
7 Demitri GD et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal
stromal tumour after failure of imatinib: a randomised controlled trial. Published online 10
October, 2006.
Source
Pfizer
3 月 26 日
196
Leading Contributors In The Progress Against Cancer To Be
Honored By World's Largest Society Of Oncology Professionals
The physician-scientist who was one of the first to investigate viable treatment options for older
patients with acute myeloid leukemia-previously believed to be fatal-and to discover that the
disease could be cured in this population using chemotherapy is among the notable awardees
set to be honored by the American Society of Clinical Oncology (ASCO).
Each year through the Special Awards Program, ASCO identifies those individuals whose
personal commitment to furthering the progress against cancer has led to tremendous
advances in the field. Clinicians, research scientists and others dedicated to improving the
lives of people living with cancer are nominated to receive ASCO's highest, most prestigious
awards. The collective efforts of this year's recipients are credited with important strides in
bettering the care of children and older adults with cancer in addition to impacting cancer
prevention and developing new treatment modalities.
"These awards recognize the best and the brightest among us, those who provide the skills
and leadership to move cancer care, research, education, and prevention forward," said
Nancy Davidson, MD, ASCO Immediate Past President and Chair of the Special Awards
Selection Committee. "I congratulate this year's group of highly accomplished individuals,
each of whom has made significant inroads in the fight against cancer. It is our honor to
bestow upon them ASCO's highest awards of achievement."
The 2009 Special Awards honorees include:
Clara D. Bloomfield, MD, is the recipient of the 2009 David A. Karnofsky Memorial Award for
her groundbreaking contributions to clinical research and for her outstanding impact on the
treatment of patients with cancer. Dr. Bloomfield was among the first physician-scientists to
investigate viable treatment options for older patients with acute myeloid leukemia-previously
believed to be fatal-and to discover that the disease could be cured in this population using
chemotherapy. Dr. Bloomfield is a Professor at The Ohio State University (OSU)
Comprehensive Cancer Center, where she also is the William G. Pace III Endowed Chair in
Cancer Research.
The Science of Oncology Award will be presented to Bert Vogelstein, MD, Director of the
Ludwig Center at Johns Hopkins, Investigator of the Howard Hughes Medical Institute, and
Clayton Professor of Oncology and Pathology at the Sidney Kimmel Comprehensive Cancer
Center. He was the first scientist to elucidate the molecular basis of a common human cancer.
In particular, he and his colleagues have demonstrated that colorectal tumors result from the
gradual accumulation of genetic alterations in specific oncogenes and tumor suppressor
genes. His group's discovery and analysis of these genes and their functions represent a
landmark in the application of molecular biology to the study of human disease.
197
Olufunmilayo Olopade, MBBS, is the Walter L. Palmer Distinguished Service Professor in
Medicine and Human Genetics, Associate Dean for Global Health, and Director of the Center
for Clinical Cancer Genetics at the University of Chicago. As an internationally recognized
hematologist/oncologist, Dr. Olopade specializes in cancer risk assessment, prevention, early
detection, and treatment of aggressive breast cancer that disproportionately affects young
women. ASCO is pleased to recognize Dr. Olopade for her outstanding efforts to reduce the
global burden of cancer. In honor of her leadership and achievements in the field of breast
cancer treatment, she will receive the ASCO-American Cancer Society Award. Dr. Olopade is
a previous recipient of an ASCO Young Investigator Award.
The B.J. Kennedy Award for Scientific Excellence in Geriatric Oncology will be presented to
Martine Extermann, MD, PhD, Associate Professor of Oncology and Medicine at the H. Lee
Moffitt Cancer Center & Research Institute at the University of South Florida. Her main interest
is understanding how the general health of the older patient interacts with the choice and the
conduct of cancer treatment. Dr. Extermann is being honored by ASCO for her outstanding
devotion to caring for older patients with cancer and for her major scientific contributions to the
field of geriatric oncology.
The 2009 Pediatric Oncology Award will be presented to the team of William E. Evans,
PharmD, and Mary V. Relling, PharmD, for their outstanding research in and devotion to the
treatment of childhood leukemia.
William E. Evans, PharmD, is Director and Chief Executive Officer of St. Jude Children's
Research Hospital, and holds the St. Jude Professorship and Endowed Chair at the University
of Tennessee Colleges of Medicine and Pharmacy. For the past 30 years, his research at St.
Jude has focused on the pharmacogenomics of anticancer agents in children, for which he has
received three consecutive National Institutes of Health (NIH) Merit Awards from the National
Cancer Institute. The major disease focus of his pharmacogenomics research is acute
lymphoblastic leukemia in children.
Mary V. Relling, PharmD, is a member and Chair of the Pharmaceutical Department at St.
Jude Children's Research Hospital, and Professor in the Departments of Pediatrics, Clinical
Pharmacy, and Pharmaceutical Sciences at University of Tennessee, Memphis. During her
time at St. Jude, Dr. Relling has focused on improving drug therapy for childhood leukemia.
Her areas of research include pharmacogenetics of antileukemia therapy and host- and
treatment-related risk factors for adverse effects of cancer therapy.
The Distinguished Achievement Award will be presented to John H. Glick, MD, for his
dedication to cancer research and his record of prominent leadership in the oncology
community. Dr. Glick is a nationally recognized medical oncologist in the areas of Hodgkin's
disease, non-Hodgkin's lymphoma, and breast cancer. His clinical research projects are
currently focused on evaluating the effectiveness of novel therapies for Hodgkin's disease,
lymphoma, and breast cancer. He is a Professor of Medicine and the Leonard and Madlyn
198
Professor of Clinical Oncology at the University of Pennsylvania School of Medicine.
Diane S. Blum, MSW, is the recipient of the Partners in Progress Award, for her dedication on
behalf of people with cancer. She is the Executive Director of CancerCare, a national nonprofit
organization that provides free, professional support services including counseling, education,
financial assistance, and practical help to people with cancer and their loved ones. In addition
to her leadership of CancerCare, Ms. Blum serves as editor-in-chief of Cancer.Net, the ASCO
website that provides oncologist-approved cancer information for patients and the public. Ms.
Blum has written and lectured extensively about the psychosocial needs of people living with
cancer and their families.
The Special Recognition Award will be presented to Richard Pazdur, MD, Director of the Office
of Oncology Drug Products in the Center for Drug Evaluation and Research of the United
States Food and Drug Administration (FDA). Dr. Pazdur's position facilitates coordination of
oncology activities across all FDA Centers and ensures ongoing outreach and collaboration
between the FDA, the National Cancer Institute, and other cancer-related organizations within
and outside of the government. Dr. Pazdur's main research interests are in clinical trial design
and drug development of anti-cancer agents in advanced colorectal cancer. He has performed
numerous phase I, II, III, and adjuvant therapy trials in this disease. ASCO is honoring Dr.
Pazdur for his achievements in cancer research and for his outstanding service to the
oncology community.
The Gianni Bonadonna Breast Cancer Award and Lecture will be presented to Carlos L.
Arteaga, MD, for his accomplishments in advancing the field of breast cancer research, in
particular his discoveries of the pathogenesis of and molecular therapeutics in breast cancer.
Dr. Arteaga is a Professor of Medicine and Cancer Biology at Vanderbilt University School of
Medicine, holds the Vice Chancellor's Chair in Breast Cancer Research, and serves as
Director of the Breast Cancer Research Program of the Vanderbilt-Ingram Cancer Center. His
research focuses on the role of signaling by growth factor receptors and oncogenes in the
progression of breast tumor cells as well as the development of molecular therapeutics in
breast cancer.
The ASCO Statesman Award recognizes ASCO members for their extraordinary volunteer
service, dedication and commitment to the Society. Recipients of the 2009 Statesman Award
have given 20 years of volunteer service and include:
Gabriel N. Hortobagyi, MD, The University of Texas M. D. Anderson Cancer Center
Scott M. Lippman, MD, The University of Texas M. D. Anderson Cancer Center
Barbara L. McAneny, MD, New Mexico Cancer Center
Monica Morrow, MD, Memorial Sloan-Kettering Cancer Center
Jamie Hayden Von Roenn, MD, Northwestern University
All of the above awards will be presented at the Society's 45th Annual Meeting taking place in
Orlando, May 29 - June 3 at the Orange County Convention Center, with the exception of the
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Gianni Bonadonna Breast Cancer Award and Lecture which will be presented at the 2009
Breast Cancer Symposium, taking place October 8 - 10 in San Francisco.
About ASCO
The American Society of Clinical Oncology (ASCO) is the world's leading professional
organization representing physicians who care for people with cancer. With more than 27,000
members, ASCO is committed to improving cancer care through scientific meetings,
educational programs and peer-reviewed journals. For ASCO information and resources, visit
http://www.asco.org/presscenter.
Patient-oriented
cancer
information
is
available
at
http://www.cancer.net.
Source
ASCO
3 月 26 日
Bio-engineered Proteins: Trial Confirms New Way To Tackle
Cancer
Re-engineering a protein that helps prevent tumours spreading and growing has created a
potentially powerful therapy for people with many different types of cancer. In a study
published in the first issue of EMBO Molecular Medicine, Canadian researchers modified the
tumour inhibiting protein, von Hippel-Lindau (VHL), and demonstrated that it could suppress
tumour growth in mice.
When solid tumours grow they often have relatively poor and disorganised blood supplies. As
a result, various regions including the centre of the tumour have low levels of oxygen and are
said to be hypoxic. Cells in these hypoxic areas produce hypoxia-inducible factor (HIF) that
helps them carry on growing. Consequently HIF is associated with aggressiveness in some of
the most common types of cancer, including prostate, breast, colon and lung cancer. Under
normal conditions VHL degrades HIF, but VHL is deactivated when oxygen levels are low. So,
in hypoxic regions of a tumour, just where VHL is needed to inhibit cancer, it is ineffective.
The researchers, therefore, created a new version of VHL that does not stop working when
oxygen is scarce. Introducing this newly engineered version of VHL into mice that had kidney
tumours dramatically reduced levels of HIF, caused tumours to regress and limited the
formation of new blood vessels within the tumours.
"We have genetically removed the Achilles' heel of VHL to permit unrestricted destruction of
HIF," says lead researcher Professor Michael Ohh, who works in the Faculty of Medicine at the
University of Toronto. "The level of HIF is usually very high under conditions of low oxygen, but
when we put in our bioengineered VHL its levels go right down to a level that would be
comparable to that in normal oxygen levels."
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Their findings could have implications for any type of cancer in which HIF plays a role. "We
used kidney cancer as a model because it is one of the most resistant tumours to conventional
radiation and chemotherapy, but our findings provide a novel concept that could potentially
serve as a foundation for smarter anti-cancer strategy for a wide variety of cancers," says Ohh.
Full citation:
Oxygen-Independent Degradation Of Hif Via Bioengineered Vhl Tumour Suppressor
Complex;
Sufan R.I., Moriyama E.H., Mariampillai A., Roche O., Evans A.J., Alajez N.M., Vitkin I.A.,
Yang V.X.D., Liu F., Wilson B.C., Ohh M.;
EMBO Mol Med 2009 1(1); DOI: emmm.200900004
About the Journal
Molecular Medicine is a rapidly-growing area of research at the interface between clinical
research and basic biology. Powerful new analytical tools provided by molecular biology allow
unprecedented insights into human physiology and the molecular basis of diseases. These
insights are being translated into better diagnosis, prevention and patient care. EMBO
Molecular Medicine is a peer-reviewed journal dedicated to the publication of original,
cutting-edge research in the field of Molecular Medicine of interest to medical and basic
scientists. The Journal publishes research articles and reviews highly relevant to all fields of
clinical medicine and their related research areas in basic biology. Studies based on model
organisms also fall within the scope of the journal, provided that the results presented are
evidently
relevant
to
human
disease.
For
more
information
please
visit
http://www.embomolmed.org.
Wiley-Blackwell's business model for new journals
EMBO Molecular Medicine will be made freely available for the first two years of publication.
Institutional customers can opt to receive complimentary online access for this journal.
Institutions may also request one complimentary print subscription when registering for online
access to EMBO Molecular Medicine. Register your institution here.
About EMBO
The European Molecular Biology Organization (EMBO) promotes excellence in molecular life
sciences by recognizing and fostering talented scientists, empowering them to advance the life
sciences to understand how life works and share knowledge to help address the challenges of
a changing world. For details about EMBO and its activities please visit http://www.embo.org.
Wiley-Blackwell was formed in February 2007 as a result of the acquisition of Blackwell
Publishing Ltd. by John Wiley & Sons, Inc., and its merger with Wiley's Scientific, Technical,
and Medical business. Together, the companies have created a global publishing business
201
with deep strength in every major academic and professional field. Wiley-Blackwell publishes
approximately 1,400 scholarly peer-reviewed journals and an extensive collection of books
with
global
appeal.
For
more
information
on
Wiley-Blackwell,
please
visit
http://www.wiley-blackwell.com or http://interscience.wiley.com.
Source
Wiley-Blackwell
3 月 26 日
Development Of Liver Cancer Prevented By Long-Term
L-Carnitine Supplementation
The study was published on March 21, 2009 in World Journal of Gastroenterology. A research
group in King Saud University, Kingdom of Saudi Arabia investigated, for the first time, the role
of carnitine, a naturally occurring compound that is synthesized mainly in the liver, during the
development of hepatocarcinogenesis. Authors of the study reported that carnitine deficiency
is a risk factor and should be viewed as a mechanism in hepatic carcinogenesis, and that
long-term L-carnitine supplementation prevents the development of liver cancer. Therefore,
carnitine supplementation alone or in combination with other natural chemopreventive
compounds could be used to prevent, slow or reverse the occurrence of liver cancer.
Chemoprevention is defined as the use of naturally occurring and/or synthetic compounds in
cancer therapy in which the occurrence of cancer can be entirely prevented, slowed or
reversed. L-carnitine is a naturally occurring compound which is primarily located in
mitochondria and possesses potential protective effects against many mitochondrial toxic
agents. It is derived from two sources; endogenous synthesis, in the liver and kidney, and from
exogenous dietary sources such as red meat and dairy products. L-carnitine is an essential
cofactor for the translocation of long chain fatty acids from the cytoplasmic compartment into
mitochondria, where beta-oxidation enzymes are located for ATP production. Despite the liver
being the main organ responsible for endogenous synthesis of L-carnitine, we were unable to
find any studies investigating the role of long-term endogenous carnitine depletion and/or
carnitine deficiency during induction of hepatic carcinogenesis.
The research team by Professor Sayed-Ahmed from College of Pharmacy, King Saud
University used an experimental model of hepatocarcinogenesis under conditions of carnitine
depletion and carnitine supplementation.
In the carnitine-depleted rat model, there were a progressive increase in the activities of liver
enzymes as well as massive degenerative changes and evidence of pre-neoplastic lesions in
liver tissues including clusters of hepatocytes with atypia and an increased proliferative rate,
diffuse bridging fibrosis and nodule formation, bile ducts with marked reactive atypia showing
nuclear enlargement, high nuclear/cytoplasmic ratio and prominent nucleoli. Interestingly,
L-carnitine supplementation resulted in a complete reversal of the increase in liver enzymes
202
compared to normal values, as well as normal liver histology with unremarkable central vein
and no evidence of pre-neoplastic lesions in liver tissues.
Due to the fact that liver cancer is one of the major health problems in the world and a large
sector of patients seek medical attention at a relatively late stage which increases the cost of
treatment, King Saud University granted Prof. Sayed-Ahmed and his colleagues a research
project with the following specific aims: (1) to understand the possible molecular mechanisms
whereby carnitine deficiency provokes hepatic carcinogenesis. (2) to understand the
relationship between hepatic cancer and its resistance to cancer chemotherapy, and (3) to
gain knowledge on the possible mechanisms by which carnitine supplementation alone or in
combination with other natural chemopreventive compounds could be used to prevent, slow or
reverse the occurrence of liver cancer.
Notes:
Reference: Al-Rejaie SS, Aleisa AM, Al-Yahya AA, Bakheet SA,Alsheikh A, Fatani AG,
Al-Shabanah OA, Sayed-Ahmed MM. Progression of diethylnitrosamine-induced hepatic
carcinogenesis in carnitine-depleted rats World J Gastroenterol 2009; 15(11): 1373-1380
http://www.wjgnet.com/1007-9327/15/1373.asp
Correspondence to: Dr. Mohamed M Sayed-Ahmed, Department of Pharmacology, College of
Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Kingdom of Saudi Arabia.
Source:
Lin Tian
World Journal of Gastroenterology
3 月 26 日
Myriad Applauds New ACOG Guidelines For Hereditary Breast
And Ovarian Cancer
Myriad Genetics, Inc. (NASDAQ: MYGN) announced its support of The American College of
Obstetricians and Gynecologists (ACOG) Practice Bulletin Number 103, dated April 2009,
which sets forth ACOG's clinical management guidelines for obstetricians and gynecologists.
These clinical management guidelines now recommend that all obstetricians and
gynecologists evaluate a patient's risk for hereditary breast and ovarian cancer syndrome as a
routine part of their obstetric and gynecologic practice. Because tailored screening and
prevention strategies can reduce morbidity and mortality from breast cancer and ovarian
cancer, the identification of individuals at inherited risk is important. Practice Bulletin 103
discusses a number of important issues involving strategies to reduce a woman's risk of breast
and ovarian cancer if she carries a mutation in BRCA1 or BRCA2. For example, women with
BRCA1 or BRCA2 mutations should be offered risk-reducing removal of the ovaries and
203
fallopian tubes by age 40 years or when child-bearing is complete.
"These new guidelines will raise physician awareness of the importance of routine hereditary
breast and ovarian cancer assessment," stated Dr. Gregory C. Critchfield, President of Myriad
Genetic Laboratories, Inc. "BRACAnalysis testing made available to at risk patients is an
important tool in helping to lower their risks of developing cancer."
Germline mutations in BRCA1 and BRCA2 account for the vast majority of families with
hereditary breast and ovarian cancer syndrome. BRCA1 and BRCA2 are tumor suppressor
genes that encode proteins that function in the DNA repair process. Although individuals with
hereditary breast and ovarian cancer syndrome inherit one defective allele in BRCA1 or
BRCA2 from their father or mother, they have a second, functional allele. If the second allele
becomes nonfunctional, cancer can develop through the accumulation of additional mutations.
When evaluating a woman's family history, families with few female relatives may
under-represent the family's risk of cancer, and therefore, the guidelines recommend that it
may be appropriate to test women with an isolated case of breast cancer at or before the age
of 50 years.
Practice Bulletin 103 further notes that many insurance companies, including Medicare, will
cover a significant portion of the expense of testing. These clinical guidelines were developed
by the ACOG Committee on Practice Bulletins-Gynecology, ACOG Committee on Genetics,
and the Society of Gynecologic Oncologists member contributors. ACOG has over 52,000
members and is the nation's leading group of professionals providing health care for women.
About BRACAnalysis
BRACAnalysis is a comprehensive analysis of the BRCA1 and BRCA2 genes for assessing a
woman's risk for breast and ovarian cancer. A woman who tests positive with the
BRACAnalysis test has an 82% risk of developing breast cancer during her lifetime and a 44%
risk of developing ovarian cancer. BRACAnalysis provides important information that we
believe will help the patient and her physician make better informed lifestyle, surveillance,
preventive medication and treatment decisions. As published in the Journal of the National
Cancer Institute, researchers have shown that pre-symptomatic individuals who have a high
risk of developing breast cancer can substantially reduce their risk of breast cancer with
appropriate preventive therapies. Additionally, as published in the New England Journal of
Medicine, researchers have shown that pre-symptomatic individuals who carry gene mutations
can lower risk of developing ovarian cancer by approximately 60% with appropriate preventive
therapies.
About Myriad Genetics
Myriad Genetics, Inc. is a leading healthcare company focused on the development and
marketing of novel molecular diagnostic and therapeutic products.
204
Myriad, the Myriad logo, BRACAnalysis, Colaris, Colaris AP, Melaris, TheraGuide, Prezeon,
Azixa and Vivecon are trademarks or registered trademarks of Myriad Genetics, Inc. in the
United States and foreign countries. MYGN-G
This press release contains "forward-looking statements" within the meaning of the Private
Securities Litigation Reform Act of 1995, including statements relating to Myriad Genetics,
Inc.'s support of The American College of Obstetricians and Gynecologists (ACOG) Practice
Bulletin Number 103, dated April 2009, which are clinical management guidelines for all
obstetricians and gynecologists; the belief that BRACAnalysis provides important information
that will help the patient and her physician make better informed lifestyle, surveillance,
preventive medication and treatment decisions; and the ability of the new guidelines to raise
physician awareness of the importance of routine hereditary breast and ovarian cancer
assessment. These "forward-looking statements" are based on management's current
expectations of future events and are subject to a number of risks and uncertainties that could
cause actual results to differ materially and adversely from those set forth in or implied by
forward-looking statements. These risks and uncertainties include, but are not limited to: the
risk that we may be unable to further identify, develop and achieve commercial success for
new products and technologies; the risk that we may be unable to discover drugs that are safer
and more efficacious than our competitors; the risk that we may be unable to develop
manufacturing capability for approved products; the risk that sales of our existing molecular
diagnostic products may decline or not continue to increase at historical rates; the risk that we
may be unable to develop additional molecular diagnostic products that help assess which
patients are subject to greater risk of developing diseases and who would therefore benefit
from new preventive therapies; the possibility of delays in the research and development
necessary to select drug development candidates and delays in clinical trials; the risk that
clinical trials may not result in marketable products; the risk that we may be unable to
successfully finance and secure regulatory approval of and market our drug candidates, or that
clinical trials will not be completed on the timelines we have estimated; uncertainties about our
ability to obtain new corporate collaborations and acquire new technologies on satisfactory
terms, if at all; the development of competing products and services; the risk that we may be
unable to protect our proprietary technologies; the risk of patent-infringement claims; risks of
new, changing and competitive technologies and regulations in the United States and
internationally; and other factors discussed under the heading "Risk Factors" contained in Item
1A in our Annual Report on Form 10-K for the year ended June 30, 2008, which has been filed
with the Securities and Exchange Commission, as well as any updates to those risk factors
filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K.
All information in this press release is as of the date of the release, and Myriad undertakes no
duty to update this information unless required by law.
Source
Myriad Genetics
3 月 27 日
205
High dosage brachytherapy obtains excellent results in
head and neck tumors
This release is available in Spanish.
High-dosage perioperative brachytherapy (applied within the surgical process) obtains
excellent results in the treatment of head and neck tumours, at the same time as reducing
the period of radiation. These are the conclusions of research undertaken jointly by three
Departments at the University of Navarra Hospital and which was published in the latest issue
of Brachytherapy, official journal of the American Society of Brachytherapy.
The work describes the application of this new radiotherapy technique to 40 patients between
2000 and 2006. Given the size of the sample, the article is a description of the greatest
number of patients treated with high-dosage brachytherapy for head and neck tumours in
world medical literature. According to results, after a seven-year follow-up, the illness was
controlled in 86% of the cases and the percentage of survival was 52%.
In concrete, the research focused on the treatment of tumours in the oral cavity, those
affecting the tongue and the floor of the mouth, and those in the oropharyngeal region, such
as tumours of the tonsils.
Involved in the study was a multidisciplinary team of seven specialists from three
departments at the University of Navarra Hospital: the Radiotherapy Department, the
Department of Oral and Maxillofacial Surgery and the Ear, Nose and Throat Department.
Intensifying radiation dosage
As is known, brachytherapy is a radiotherapy treatment involving the placing of radioactive
sources within the tumour or nearby.
In the case in hand, the work analysed the application of brachytherapy as complementary
post-surgery treatment, explained Doctor Rafael Martínez-Monge, Director of the
Radiotherapy Department. Some cases of head and neck tumours require the application of
radiotherapy after the surgical operation. Using this technique, they have managed to
intensify the radiation dosage with the goal of reducing relapse rates.
In certain treatments, brachytherapy provides better end-result possibilities than
conventional radiotherapy. The procedure enables the administration of doses that would not
be easily achieved using other techniques, due to toxic effects, explained the specialist from
the University of Navarra Hospital.
Two weeks of treatment less
206
Moreover, the use in brachytherapy of high dosages involves a series of benefits for the
patient as regards the overall treatment. The great advantage, points out Doctor
Martínez-Monge, is the reduction of total time. While conventional radiotherapy treatment
lasted seven weeks, administering part of the radiation through brachytherapy can take two
weeks less.
This technique also manages to reduce the time of radiation compared to treatment with low
dosage brachytherapy. Thanks to the existence of new sources of radiation, the treatment is
released in a matter of minutes. Before the patient under brachytherapy treatment carried
the radioactive source for several days and, thus, had to be isolated in a lead-lined room, with
limitations on visits and nursing care. With high-dosage brachytherapy, however, the patient
is only radioactive during the actual administration of the treatment; as such, the rest of the
time can be spent in a conventional room.
For the administration of this technique it is necessary to prepare the affected region during
the surgical operation. On extirpating the tumour, the surgeon covers the surgery zone — the
area with greatest possibilities for relapse — with a series of plastic tubes which are
subsequently filled with radioactive material, the aim being to effect a highly selective and
precise radiation. Brachytherapy is introduced through these tubes, one end of which appears
at the surface of the skin, like a drainpipe, explained Doctor Rafael Martínez-Monge. These
tubes are connected to a machine that administers the treatment according to a computer
programme personalised for each patient, he added.
Application to other types of tumour
Apart from perioperative high-dosage brachytherapy treatment for head and neck tumours,
the University of Navarra Hospital has been working on the application of this procedure to
other oncological processes for a number of years. There are a number of studies under way
on its use in gynaecological tumours and sarcomas, amongst others. Since 2000 about 400
patients, with different types of tumours, have been treated with this technique.
3 月 27 日
Skin cancer study uncovers new tumor suppressor gene
Genetic analysis of key group of enzymes may pave the way for more individualized
treatments
National Institutes of Health (NIH) researchers have identified a gene
that suppresses tumor growth in melanoma, the deadliest form of skin
cancer. The finding is reported today in the journal Nature Genetics as
part of a systematic genetic analysis of a group of enzymes implicated
in skin cancer and many other types of cancer.
207
The NIH analysis found that one-quarter of human melanoma tumors had
changes, or mutations, in genes that code for matrix metalloproteinase
(MMP) enzymes. The findings lay the foundation for more individualized
cancer treatment strategies where MMP and other key enzymes play a
functional role in tumor growth and spread of the disease.
Tumor suppressor genes encode proteins that normally serve as a brake on
cell growth. When such genes are mutated, the brake may be lifted,
resulting in the runaway cell growth known as cancer. In contrast,
oncogenes are genes that encode proteins involved in normal cell growth.
When such genes are mutated, they also may cause cancer, but they do so
by activating growth-promoting signals. Cancer therapies that target
oncogenes usually seek to block or reduce their action, while those aimed
at tumor suppressor genes seek to restore or increase their action.
The new study may help to explain the disappointing performance of drugs
designed to treat cancer by blocking MMP enzymes. Because members of the
MMP gene family were thought to be oncogenes and many tumors express high
levels of MMP enzymes, researchers have spent decades pursuing MMPs as
promising targets for cancer therapies. However, when MMP inhibitors were
tested in people with a wide range of cancers, the drugs failed to slow
-- and in some cases even sped up -- tumor growth.
Now, it turns out that one of the most often mutated MMP genes in melanoma
is not an oncogene at all. In its study, the team led by researchers from
the National Human Genome Research Institute (NHGRI) found that MMP-8
actually serves as a tumor suppressor gene in melanoma. Consequently, in
the estimated 6 percent of melanoma patients whose tumors harbor a mutated
MMP-8 gene or related tumor suppressor(s), it may not be wise to block
all MMPs. The study suggests that a better approach may be to look for
drugs that restore or increase MMP-8 function or for drugs that block only
those MMPs that are truly oncogenes.
"This research is an illustrative proof of concept that shows the value
of genomic strategies for understanding cancer and possible therapies,"
said NHGRI Scientific Director Eric Green, M.D., Ph.D. "It is gratifying
to see that genomic technologies are guiding scientific discovery,
advancing cancer research, especially melanoma research."
Melanoma is the most serious form of skin cancer. In the United States
and many other nations, melanoma is becoming more common every year. A
major cause is thought to be overexposure to the sun. The ultraviolet
radiation in sunlight can damage DNA and lead to cancer-causing genetic
changes within skin cells.
208
MMP enzymes help the body to break down and recycle proteins, playing a
crucial role in the process of remodeling skin after sunburns, cuts or
other injuries. The MMP gene family has been associated with tumor growth
in a variety of cancers, including breast, colon and melanoma.
To explore the role of MMP genes in melanoma, the NHGRI researchers studied
a bank of tumor and blood samples collected from 79 patients with
aggressive melanoma by collaborator Steven Rosenberg, M.D., Ph.D., chief
of surgery at the National Cancer Institute (NCI). Specifically, they
compared the sequence of MMP genes in tumors and normal DNA from the same
patients, looking for mutations in all 23 members of the MMP gene family.
The researchers identified 28 different mutations in eight MMP genes in
the melanoma tumors studied. These mutations were found to be distributed
in different frequencies and patterns among the tumor samples. Nearly
one-quarter of the tumors analyzed had at least one MMP gene mutation.
Some mutations were found in as few as 3 percent of tumors, while more
than 6 percent of tumors had mutations in MMP-8 and more than 7 percent
had mutations in MMP-27, which codes for an enzyme very similar to MMP-8.
"We often talk about cancer as though it is one disease, and cancers do
have many common denominators. But when we look at the DNA level, we see
that different cancers have different genetic profiles, and so do
different patients who have the same cancer," said the study's senior
author, Yardena Samuels, Ph.D., an investigator in the Cancer Genetics
Branch of the NHGRI's Division of Intramural Research.
Dr. Samuels and her collaborators followed up their DNA sequencing work
with cell and animal studies to see whether MMP-8 mutations affect enzyme
function. Strikingly, the researchers showed that five of the mutations
reduced activity of the MMP-8 enzyme. The researchers next studied whether
MMP-8 mutations promote activities related to cancer. Indeed, cells with
MMP-8 mutations showed increased ability to multiply outside the
constraints of normal cells, a hallmark of cancer development known as
anchorage-independent growth. Likewise, cells with MMP-8 mutations had
a greater ability to migrate -- a key aspect of cancer metastasis -- than
normal cells.
The researchers found that mice injected with cells expressing normal
MMP-8 did not develop skin ulcers, which are one of the most important
measures of cancer aggression in melanoma. In contrast, mice injected with
cells expressing mutated MMP-8 went on to develop ulcerations and
metastases in their lungs.
###
209
In addition to Dr. Samuels's and Dr. Rosenberg's laboratories, the NIH
team included researchers from the National Institute on Aging and the
National Institute of Dental and Craniofacial Research, who helped with
the mouse studies; and NHGRI's Genome Technology Branch, Bioinformatics
and Scientific Programming Core, and Office of Laboratory Animal Medicine.
Other collaborators included researchers from the Sidney Kimmel
Comprehensive Cancer Center at Johns Hopkins in Baltimore, and the
University of South Carolina School of Medicine in Columbia.
NHGRI is one of the 27 institutes and centers at the NIH, an agency of
the Department of Health and Human Services. The NHGRI Division of
Intramural Research develops and implements technology to understand,
diagnose and treat genomic and genetic diseases. Additional information
about NHGRI can be found at its Web site, www.genome.gov.
The National Institutes of Health — "The Nation's Medical Research
Agency" — includes 27 institutes and centers, and is a component of the
U.S. Department of Health and Human Services. It is the primary federal
agency for conducting and supporting basic, clinical and translational
medical research, and it investigates the causes, treatments and cures
for both common and rare diseases. For more, visit www.nih.gov.
3 月 27 日
Getting down to cancer basics
Cancer mutations in the heart of gene regulation
Researchers have identified a new cancer gene - one that is common to many
cancers and affects the most basic regulation of our genes. The new example
- a gene on the X chromosome called UTX - is found in 10% of cases of
multiple myeloma and 8% of esophageal cancers.
UTX plays a role in overall regulation of the activity of many genes and
it is possible that other genes with similar roles will also be found to
be involved in different tumor types. This is the first example of
mutations in a gene of this functional class. The finding arose from a
study of mutations in 4000 genes in kidney cancer.
"UTX is an important component of the transcriptional control machinery
- it influences some of the most fundamental mechanisms controlling gene
activity in our cells," explains Dr Andy Futreal, co-leader of the Cancer
Genome Project at the Wellcome Trust Sanger Institute. "Unlike many cancer
210
genes, UTX does not appear to be directly involved in cell division or
cell death but in basic gene regulation and shows the depths to which
cancers will plumb in order to get themselves ready to go."
The normal UTX protein modifies part of the structure holding DNA together
in our cells. The composite DNA–protein structure, called chromatin, is
not simply a scaffold, but plays an active role in controlling gene
activity. The UTX protein alters a key organising subunit component of
chromatin, called a histone. The protein is likely to be involved in both
turning genes on and off, making it a key regulator of the yin-yang of
gene control.
In the massive DNA sequencing study, the team found rare mutations of the
UTX gene in clear cell renal cancer - a type of kidney cancer. When they
expanded the search they found mutations in many cancer types - including
one in ten multiple myeloma and one in twelve esophageal cancer cases.
"This work shows that mutations in genes with different functions can be
found in human cancer through systematic approaches. These results
indicate that cancer genes are not restricted to 'classical' roles of
survival and cell proliferation, but can affect a variety of other
cellular mechanisms," explains Professor Victor Velculescu, Associate
Professor of Oncology and Director of Cancer Genetics from the Ludwig
Center at Johns Hopkins and co-Director of Cancer Biology, at Johns
Hopkins Kimmel Cancer Center. "UTX wouldn't have been found without this
high-throughput type of study and indicates the type of novel findings
we might expect from the International Cancer Genome Consortium."
The International Cancer Genome Consortium (ICGC) seeks to catalogue
genetic abnormalities in 50 different tumour types. The possibility of
uncovering new regulatory genes - like UTX - along with continued efforts
to catalog cancer genes, will boost researchers' attempts to
comprehensively describe different cancers which will to lead to
expanding opportunities to reduce the global cancer burden.
The team showed that the biology of the mutation fitted their prediction.
Cells that lacked a functional UTX gene showed notable slowing of growth
when a copy of normal UTX was reintroduced. As well, substantial changes
in gene transcription were noted. Genes with the most significant changes
in expression were highly enriched in those most susceptible to control
by UTX mediated histone modification.
The work identifies a new class of cancer genes that researchers can now
pursue. These are genes that occupy the central control position of gene
211
activity and act to keep cells from turning cancerous. When such 'tumor
suppressor genes' are inactivated, other genes can run riot.
The consequence of mutation in UTX is to bring about changes in activity
of other genes through epigenetic changes - their activity is changed by
modification, not of their DNA code, but of their associated proteins and
chemical tags.
"This is a genetic change with consequences at the level of epigenetic
regulation," explains Professor Mike Stratton, co-leader of the Cancer
Genome Project at the Sanger Institute. "When we look at cancers, a
substantial proportion of the epigenetic disregulation may well have a
genetic basis."
3 月 27 日
Mayo Clinic researchers discover and manipulate
molecular interplay that moves cancer cells
JACKSONVILLE, Fla. — Based on research that reveals new insight into mechanisms that
allow invasive tumor cells to move, researchers at the Mayo Clinic campus in Florida have a
new understanding about how to stop cancer from spreading. A cancer that spreads
elsewhere in the body, known as metastasis, is the process that most often leads to death
from the disease.
In the March 29 online issue of Nature Cell Biology, researchers say that a molecule known as
protein kinase D1 (PKD1) is key to the ability of a tumor cell to "remodel" its structure,
enabling it to migrate and invade. The researchers found that if PKD1 is active, tumor cells
cannot move, a finding they say explains why PKD1 is silenced in some invasive cancers.
During metastasis, invasive cancer cells respond to biological signals to move away from a
primary tumor. Multiple research groups at Mayo Clinic in Florida are especially interested in
this process. One team, led by cancer biologist Peter Storz, Ph.D., has been investigating a
process known as actin remodeling at the leading edge - the most forward point - of these
migrating tumor cells.
"The events that reorganize the actin cytoskeleton at the leading edge are complex — a
multitude of molecules act in concert," Dr. Storz says. "But it appears that PKD1 must be
turned off if cancer cells are to migrate."
Actin filaments help make up the cytoskeleton of cells. For cancer cells to move, the
actin-based cell structure has to be continually reorganized, Dr. Storz says, and to do this,
new actin filaments need to be generated to shift the cell forward.
212
Dr. Storz' group discovered that PKD1 was critical to this process. The researchers found that
PKD1 inhibits another protein known as slingshot, which regulates the severing of existing
actin structures so that new actin filaments can be synthesized, an event that is essential for
cell movement.
The researchers used methods to deplete tumor cells of PKD1 and found that their motility
increased. They then expressed activated PKD1 in tumor cells and found that movement was
blocked. PKD1 is therefore a negative regulator of directed cell migration, and if PKD1 is not
expressed in tumor cells, slingshot will become active and will contribute to the
reorganization of actin, and a tumor cell will move, according to researchers.
"This makes sense, because other investigators have found that PKD1 is down-regulated, or
turned off, in invasive forms of gastric, prostate, and breast cancer," says Dr. Storz.
So far, investigators have identified a number of players along the pathways that regulate
cancer cell movement, from the molecule (RhoaA) that activates PKD1, to the well-known
protein (cofilin) that disassembles actin filaments and which is regulated by slingshot. When
PKD1 is activated, cofilin does not function and so the cell cannot move.
"Now that we have identified PKD1 as key regulator in processes regulating actin-based
directed tumor cell movement, we can begin to think about designing treatments to stop
invasive cancer cells from metastasizing," says Dr. Storz. "The basic mechanisms we have
uncovered are key to developing those strategies."
###
Co-authors include Tim Eiseler, Ph.D., Heike Döppler, and Irene Yan from the Mayo Clinic
Department of Cancer Biology; and Kanae Kitatani, Ph.D., and Kensaku Mizuno, Ph.D., from
the Graduate School of Life Sciences at Tohoku University in Japan.
The study was funded by Mayo Foundation and the Mayo Comprehensive Cancer Center, the
National Cancer Institute, a 'Friends for an Earlier Breast Cancer Test' Grant, and by a
grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science,
and Technology of Japan.
To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news.
MayoClinic.com (www.mayoclinic.com) is available as a resource for your health stories.
3 月 27 日
An International Team Of Scientists Led By The UPC Is Designing A System To
Support The Diagnosis Of Brain Tumors
The Artificial Intelligence Decision Tools for Tumour Diagnosis (AIDTumour) project is being
funded by the Interministerial Commission for Science and Technology (CICYT) and directed
213
by Alfredo Vellido, a member of the UPC Soft Computing (SOCO) research group. Vellido is
coordinating a team of 14 researchers in creating a functional prototype that will assist doctors
in improving diagnosis in clinical oncology, in particular of brain tumors, based on magnetic
resonance spectroscopy data. This is a cutting-edge initiative in the field of medical
decision-making support systems, an area in which Spain has been lagging behind the rest of
Europe.
Multidisciplinary research
In addition to the SOCO research group of the UPC's Department of Software, the team is
made up of scientists from Liverpool John Moores University, the University of Manchester,
and the NHS Clatterbridge Centre for Oncology in Bebington in the United Kingdom (a leading
country in research into oncology decision-making support systems), as well as the Integrated
Reasoning Group of the National Research Council Canada. The Group for Biomedical
Applications of Nuclear Magnetic Resonance Spectroscopy (GABRMN) of the Universitat
Autònoma de Barcelona has collaborated on the project by providing the medical data.
Companies and hospitals, including Aleasoft, Microart, Vall d'Hebron Hospital, Bellvitge
University Hospital, Sant Joan de Déu Hospital, Barcelona Biomedical Research Park, and
Cetir Grup Mèdic, have expressed an interest in the project, both in the development of its
theoretical aspects and in the possibility of implementing the new system to support clinical
diagnosis.
Diagnosis support technology
The scientists participating in the AIDTumour project are seeking to create technology that
supports the diagnosis of brain tumors. Thus they do not intend to create a decision-making
system but rather one that would assist the specialist and become a kind of "second opinion"
in the medical diagnosis, which is particularly important in the field of oncology.
The type of brain tumor investigated in the project is not easy to diagnose with certainty. In fact,
the best way to be certain of the diagnosis of a tumor is to perform a biopsy but unfortunately
this is not advisable where a brain tumor is concerned. In this area, doctors and radiologists
have to work with non-invasive techniques and this creates a series of restrictions.
The multi-centre data used on the project are spectra obtained using nuclear magnetic
resonance. Some of the frequencies of these spectra may be related to the presence of
different chemical compounds in a tumor, which serve as indicators. Based on the observation
of these indicators, the few doctors who are expert in the interpretation of these data are
usually capable of recognizing each tumor. In contrast, a machine is capable of working with
data populations and making use of much richer information.
In fact, the system being developed by the SOCO group is especially useful in ambiguous
cases. When anomalies are present, these can be due to an atypical tumor or simply due to
214
measurement problems. It has been shown that these atypical cases can be better
characterized and visualized with the new diagnosis support system, since the machine can
detect an anomalous case by comparing it with other anomalous cases and then propose
hypotheses that could explain the anomaly. This can therefore assist doctors in making
informed decisions in clinical diagnosis.
Currently the project is in the final stage of prototype design and the SOCO group is focusing
its efforts on integrating these tools into a system of decision support with advanced
visualization techniques. The aim is to make the system more advanced, intuitive, and
comfortable to use. A prototype is being designed to enable subsequent manufacture of an
effective tool to support medical specialists and it will be used this year on an experimental
basis at the NHS Clatterbridge Centre for Oncology in Bebington, one of the British
participants in the project.
The results of the AIDTumour project research have been recently disseminated through
various conferences and international journals including the publications Neural Networks,
Neurocomputing, Computers in Biology and Medicine and Biomedical Signal Processing &
Control.
About soft computing
The term "soft computing" was coined in the mid-nineties to describe the combined use of
different computing techniques that have been developed over the last thirty years, including
fuzzy systems, neural networks and evolutionary algorithms.
What these methodologies have in common is that they abandon binary logic, static analytical
models, rigid classifications, and determinist searches in approaching real-world problems that
are incompletely or badly defined and therefore difficult to model. In these cases, precise
models may simply not exist or they may be too impractical or costly to implement. Thus it is
necessary to use approximate reasoning systems capable of processing such far-from-perfect
information in a flexible way. These types of systems and the methodologies they are based
upon with fall within the field of soft computing.
Universitat Politècnica de Catalunya
http://www.upc.edu/es
3 月 27 日
Researchers Build Computer Simulations Of Laser-Nanoparticle Treatments For
Cancer
Two lasers may be better than one when attacking cancer cells, according to a paper by Rice
University scientists.
Yildiz Bayazitoglu, Rice's H.S. Cameron Chair Professor of Mechanical Engineering and an
authority on heat transfer and fluid flow, and doctoral student Jerry Vera are using computer
simulations to quantify the effect of heating nanoparticles with near-infrared lasers to kill
215
cancer tumors without damaging healthy tissue.
They hope to raise the efficiency of destroying tumors by fine-tuning methods of heating them
based on the size and composition of not only the tumor but also the surrounding tissue.
The paper summarizing their results, "Gold Nanoshell Density Variation with Laser Power for
Induced Hyperthermia," is published in the January issue of the International Journal of Heat
and Mass Transfer.
The researchers found that attacking a tumor with two lasers can heat it more thoroughly than
a single laser. For tumors as large as one centimeter, simulations showed opposing lasers
surgically inserted via fiber optics in a minimally invasive procedure produced the most uniform
temperature profile in every case.
Lasers and nanoparticles are already being used to treat cancer. A Houston company founded
by Rice scientists Jennifer West and Naomi Halas, Nanospectra Biosciences, Inc., is
conducting human tests of a system that uses nanoshells heated by near-infrared lasers to kill
tumors. Bayazitoglu, West and Halas are all part of Rice's Laboratory for Nanophotonics.
The Bayazitoglu group's approach would refine such treatment by taking into account the
light-scattering properties of nanoparticles. Their concern is that nanoparticles near the
surface of a tumor will block a laser from reaching those at the center.
"Think about it this way: If you're driving on a very foggy night, you can only see just so far no
matter how good your headlights are," wrote Vera in an article about the research. "That's
because the millions of small water droplets in the air absorb and scatter the light, deflecting
the beams from your headlights before they can reflect off of whatever's ahead of you on the
road.
"Nanoparticles dispersed within a tumor do exactly the same thing. They're very good at
absorbing laser light and generating heat, but within particularly thick tumors, that same quality
prevents a lot of the light from reaching deeper into the tissue."
Bayazitoglu said this phenomenon, called "extinction," is "highly undesirable." A uniform
temperature profile of at least 60 degrees Celsius has to be created to kill the whole tumor.
"Raising the temperature on one end but not the other will simply allow the tumor to re-grow,
and that doesn't solve the problem - or cure the patient."
The density and placement of nanoparticles in the tumor are important, said Bayazitoglu.
"Ideally, you should put nanoparticles at the center of the tumor, then kill it from the center out,"
she said.
Laser treatment may be effective even if nanoparticles are not used, she said. "If the tumor has
good absorption properties, slow heating can do a good job of killing the cancer, because the
216
heat has time to get inside. If you're doing that, sometimes it's better not to use nanoparticles."
With so many tissue types and the great variety of cancers people face, the importance of
accurate simulations cannot be overemphasized, the researchers said. They hope the ability
to calculate scenarios will allow doctors to find the best laser therapy to produce the perfect
heating environment.
Notes:
The research was funded by the Alliances for Graduate Education and the Professoriate
program through the National Science Foundation.
The paper can be viewed at: http://tinyurl.com/dx7qlj
An article by Vera on the research can be found here.
Source:
Mike Williams
Rice University
3 月 27 日
Discovery May Result In New Test To Determine Predisposition To Cancer
Researchers at UCLA's Jonsson Comprehensive Cancer Center have developed an assay
that may be used to help identify new genes that can predict a predisposition to cancer.
The study, published in the April issue of Radiation Research, was done in yeast and
mammalian cells.
Cancer cells show persistent genetic instability and the researchers, led by Robert Schiestl,
have discovered a mechanism that switches on that genetic instability. If they can uncover and
understand the molecular pathways at work in promoting genetic instability, they may be able
to develop ways to switch that mechanism off, restoring stability.
"We all have several hundred cells in our body that go crazy every day, and they're taken out
by our immune system," said Schiestl, a professor of pathology, radiation oncology and
environmental health sciences and a Jonsson Cancer Center scientist. "What's important is
that those cells don't grow and spread and invade other regions of our body. Cancer cells are
able to grow, spread and invade because the continued genetic instability can disturb the
cellular program and create a growth advantage. Unfortunately, the immune system is not very
effective at taking cancer cells out."
The assay determines the efficiency of the repair mechanism when DNA suffers a
double-strand break, when both strands in the double helix are severed. These breaks cause
genetic instability and are particularly dangerous because they can lead to genome
217
rearrangements or deletions of certain genes that, when gone, result in cancer.
"Every cell has double strand breaks all the time," said Schiestl, senior author of the study. "It
is how the cell tries to fix these breaks that is key, the capacity and the efficiency of the repair
so no further harm occurs."
A cell that can't efficiently repair itself could result in cancer.
In the study, researchers irradiated cells to create double strand breaks. They wanted to
determine if a double strand break occurs in one area of the DNA is the instability limited to
that area or also evident elsewhere. The standard thinking was that the genetic instability
would be localized to the area of the break. However, Schiestl and his team showed that a
break in one area has an "in trans" effect, meaning the instability could surface anywhere.
"What we have shown now in this paper is that DNA damage at one position in the genome,
causes a certain mechanism of genetic instability all over the genome," Schiestl said.
Specifically, the team irradiated cells and then transformed them with a DNA fragment that
detects the efficiency and the accuracy of double strand break repair. The key in this
experiment was that the DNA fragment was not irradiated. In this way, the researchers could
demonstrate that the radiation triggered a specific mechanism of double strand break repair in
the DNA fragment that did not receive any radiation. The effect was still noticeable after almost
all the DNA damage the radiation caused in the cells was repaired, showing that the
mechanism that is induced by the radiation is independent of the actual damage caused by the
radiation.
Schiestl had previously shown that a single DNA double strand break also induces genetic
instability all over the genome at sites that are not damaged, again a proof that double strand
breaks induce genetic instability in trans.
Interestingly, many cancer cells show an elevated induction of the specific DNA double strand
break repair mechanism found induced in trans in this study, as if the cancer cells had this
mechanism somehow induced and were not able to switch it off.
"Now we have to identify the mechanism of the pathway, identify the genes involved in
inducing that pathway and that might give us targets that we can inhibit with drugs to try to
reduce genetic instability," Schiestl said. "That could lead to a cancer treatment. Any time you
can stop the growth of a cancer, you've won. It doesn't damage other tissues or spread to
other organs. We might be able to stop the instability before it results in cancer."
Notes:
The research was funded in part by a National Institutes of Health grant and a NASA graduate
student fellowship. Other members of Schiestl's team included Zorica Scuric, Cecilia Chan and
218
Kurt Hafer.
UCLA's Jonsson Comprehensive Cancer Center has more than 350 researchers and
clinicians engaged in disease research, prevention, detection, control, treatment and
education. One of the nation's largest comprehensive cancer centers, the Jonsson center is
dedicated to promoting research and translating basic science into leading-edge clinical
studies. In July 2008, the Jonsson Cancer Center was named among the top 10 cancer
centers nationwide by U.S. News & World Report, a ranking it has held for nine consecutive
years.
Source:
Kim Irwin
University of California - Los Angeles
3 月 27 日
Multiple Enzymes In Cancer Pathway Knocked Out By New Drug Agent
A team of 24 researchers from the U.S., Europe, Taiwan and Japan and led by University of
Illinois scientists has engineered a new anti-cancer agent that is about 200 times more active
in killing tumor cells than similar drugs used in recent clinical trials.
The study appears this week in the Journal of the American Chemical Society.
The new agent belongs to a class of drugs called bisphosphonates. These compounds were
originally developed to treat osteoporosis and other bone diseases, but were recently found to
also have potent anti-cancer and immune boosting properties.
Drug developers have tried for years to design drugs to inhibit cell survival pathways in tumor
cells, focusing on a protein called Ras since nearly a third of all human cancers involve a
mutation in the Ras gene that causes cell signaling to go awry. These efforts have met with
limited success.
Bisphosphonates act on other enzymes, called FPPS and GGPPS, which are upstream of Ras
in the cell survival pathway. Inhibiting these enzymes appears to be a more effective strategy
for killing cancer cells.
When used in combination with hormone therapy in a recent clinical trial, the bisphosphonate
drug zoledronate significantly reduced the recurrence of breast cancer in premenopausal
women with estrogen-receptor-positive breast cancer. Similar results were reported previously
for hormone-refractory prostate cancer.
But zoledronate quickly binds to bone, reducing its efficacy in other tissues.
"We're trying to develop bisphosphonates that will be very active but won't bind to the bone,
because if they bind to the bone they're not going to go to breast, lung or other tissues," said
219
University of Illinois chemistry professor Eric Oldfield, who led the new study.
Oldfield's team also wanted to design a compound that would inhibit multiple enzymes in the
tumor cell survival pathway, rather than just one, an approach analogous to the use of
multi-kinase inhibitors in cancer therapy.
Andrew Wang, of Academia Sinica, Taipei, and Illinois chemist Rong Cao began by producing
crystallographic structures of the target enzymes and drug candidates, allowing the
researchers to identify those features that would enhance the drugs' ability to bind to the
enzymes. Using this and other chemical data, Illinois chemistry department research scientist
Yonghui Zhang engineered new bisphosphonate compounds that bound tightly to multiple
enzyme targets, but not to bone.
One of the new compounds, called BPH-715, proved to be especially potent in cell culture and
effectively inhibited tumor cell growth and invasiveness.
Tadahiko Kubo, of Hiroshima University, then found that BPH-715 also killed tumor cells in
mice. And Socrates Papapoulos, of Leiden University, the Netherlands, showed that the
compound had a very low chemical affinity for bone.
In humans, compounds like BPH-715 and zoledronate have an added benefit in fighting
cancer: They spur the proliferation of immune cells called gamma delta T-cells, which aid in
killing tumor cells.
"The new drugs are about 200 times more effective than the drugs used in recent clinical trials
at killing tumor cells and in activating gamma delta T-cells to kill tumor cells," Oldfield said.
"They also prevent tumor progression in mice much better than do existing bisphosphonate
molecules."
Source:
Diana Yates
University of Illinois at Urbana-Champaign
3 月 27 日
NICE Recommends Sunitinib For The First-line Treatment Of Renal
Cancer
The National Institute for Health and Clinical Excellence (NICE) has issued final guidance
recommending the use of sunitinib as a first-line treatment option for people with advanced
and/or metastatic renal cell carcinoma who are suitable for immunotherapy and who are well
enough to tolerate the treatment.
Andrew Dillon, NICE Chief Executive said: Following extensive consultation, I'm very pleased
that we are now able to issue this important guidance in its final form."
About this appraisal
220
1. The guidance on first line use of sunitinib has been developed on the understanding that the
currently available treatment for advanced and/or metastatic renal cell carcinoma is
immunotherapy (namely interferon-alfa and interleukin-2). The Institute recognises that there
are people who have had or who are currently receiving immunotherapy and wish to clarify the
implications of the guidance for these people. Sunitinib can be considered as a treatment
option for those people with advanced and/or metastatic RCC who are currently receiving
immunotherapy or who have had immunotherapy before the release of our final
recommendations to ensure they are not disadvantaged by our proposed guidance.
2. NICE has been appraising the use of bevacizumab, sorafenib, sunitinib and temsirolimus for
the treatment of advanced and/or metastatic renal cell carcinoma. Following the independent
advisory Committee meeting on 14 January 2009 NICE has decided to split this appraisal in
two in order to get guidance out to the NHS as quickly as possible.
3. NICE is also appraising the use of bevacizumab, sorafenib and temsirolimus for first-line
treatment options for advanced and/or metastatic renal cell carcinoma and the two drugs also
licensed for second-line treatment of advanced or metastatic renal cell carcinoma, sorafenib
and sunitinib, guidance is expected to be published later this year.
About NICE
4. The National Institute for Health and Clinical Excellence (NICE) is the independent
organisation responsible for providing national guidance on the promotion of good health and
the prevention and treatment of ill health.
5. NICE produces guidance in three areas of health:
- public health - guidance on the promotion of good health and the prevention of ill health for
those working in the NHS, local authorities and the wider public and voluntary sector
- health technologies - guidance on the use of new and existing medicines, treatments and
procedures within the NHS
- clinical practice - guidance on the appropriate treatment and care of people with specific
diseases and conditions within the NHS.
Source
NICE
3 月 28 日
BioMosaics' Glypican-3 Antibody (clone 1G12) Validated At PhenoPath
Laboratories For Immunohistochemical Detection Of Liver Cancer
BioMosaics Inc., a cancer biomarker development company, announced that its monoclonal
antibody product (clone 1G12) for detection of Glypican-3 (GPC3) has been validated for use
221
as an immunohistochemical test for diagnosis of Hepatocellular Carcinoma (HCC) by
PhenoPath Laboratories. PhenoPath Laboratories is a state-of-the-art reference pathology
laboratory providing diagnostic immunohistochemistry (IHC), in situ hybridization (ISH), flow
cytometry, and other molecular pathology services to pathologists throughout the United
States.
"We are pleased that PhenoPath has added the 1G12 Glypican-3 antibody to its test menu.
Immunohistochemistry using this antibody provides added specificity to the identification of
HCC in patient tissue samples," said Dr. Mark Allegretta, BioMosaics Chief Scientific Officer.
PhenoPath is CLIA-certified and accredited by the College of American Pathologists. In
addition to testing performed at PhenoPath, the antibody is available in concentrated form
(BioMosaics Catalog # B0055 and B0025), or as a ready-to-use, pre-diluted product for IHC
(Catalog # B0134). Both formats are suitable for use with manual protocols or in automated
immunostaining instruments.
The antibody validation studies were performed with formalin fixed paraffin embedded tissue
sections used in routine immunohistochemistry tests. For validation, a series of tissues
(normal & tumor) that would be part of the differential diagnosis in a clinical setting were tested
to determine what percent might be positive. With the 1G12 antibody to GPC3, 88% (38/43) of
cases with hepatocellular carcinoma showed strong positive immunostaining. In all observed
cases, non-neoplastic liver that was present in the specimen was negative or showed rare
cells positive for Glypican-3. All 21 cases of nodules in cirrhotic liver were negative for
Glypican-3.
Primary Liver Cancer, or Hepatocellular Carcinoma, is one of the most common and
aggressive malignant tumors worldwide, causing an estimated one million deaths annually.
The main causative agents are hepatitis B virus (HBV), hepatitis C virus (HCV), as well as
alcoholic cirrhosis and non-alcoholic steatohepatitis (NASH) which is associated with obesity
and diabetes. The incidence of HCC has been steadily increasing over the past ten years and
is expected to continue to rise over the next decade.
Glypican-3, an oncofetal antigen, is a member of the glypican family of GPI-anchored
cell-surface heparan sulfate proteoglycans. Many studies have shown that, using the 1G12
antibody, GPC3 is detected at the protein level by immunohistochemistry in most cases of
primary liver cancer, including small tumors. It is undetectable in normal liver and benign
hepatic lesions. Glypican-3 has been identified as one of the earliest proteins detected in HCC.
Recent validation studies using BioMosaics GPC3 1G12 monoclonal antibody have confirmed
the early presence of GPC3 on HCC biopsies and in a percentage of highly dysplastic cirrhotic
nodules. This class of dysplastic nodule is considered to be an early form of HCC, and
immunohistochemical studies show that they are routinely negative for alpha fetoprotein.
Glypican-3 therefore has considerable promise as a biomarker for early detection of HCC.
About BioMosaics
222
BioMosaics is a biotechnology company located in Burlington VT engaged in the development
and commercialization of innovative products for the early diagnosis, prediction, and
monitoring of cancer. http://www.biomosaics.com
About PhenoPath Laboratories
PhenoPath Laboratories is a physician-owned pathology reference laboratory providing
diagnostic and contract research services to hospitals, physician offices, surgery centers,
biopharmaceutical
companies
and
research
institutions
nationwide.
http://www.phenopath.com
BioMosaics Inc.
http://www.biomosaics.com
3 月 28 日
Mechanism That Regulates Cancer-Causing Gene, Revealed By URI
Scientists
Two University of Rhode Island scientists have revealed how a cancer causing protein is
regulated by reactive oxygen species (ROS) -- a type of stress signal. Their findings provide
new insight into how this protein normally behaves in human cells and may help in the design
of drugs targeting specific cancers.
Doctoral student David J. Kemble and Professor Gongqin Sun in the URI Department of Cell
and Molecular Biology are the first to provide a biochemical mechanism describing how certain
protein tyrosine kinases sense and respond to oxidation. This sensing system was found to
uniquely apply to two families of proteins implicated in numerous cancers: the Src and
Fibroblast Growth Factor Receptor families of tyrosine kinases.
Their results were published online March 9 in the Proceedings of the National Academy of
Sciences.
Src was the first enzyme identified as a cancer-causing gene in the early 1900's. For years
scientists have been studying how the enzymes are expressed in cancer cells - what do they
do and what controls them.
According to Kemble and Sun, Src is a master regulator of cell function, controlling cell
metabolism, division, and death. In normal cells, the function of Src is turned off, and it is
turned on only when certain stimulatory signals activate it. When the regulatory mechanisms
that control Src activity are disrupted, Src may be turned on all the time, which turns the host
cell into a cancer cell. Thus, it is crucial to understand how Src function is controlled.
Reactive oxygen species have long been viewed as damaging byproducts of oxygen-based
metabolism. However, it is now recognized that ROS are produced when the cells are under
growth stimulation, and they in turn regulate other cellular events. Accumulating evidence
indicates that ROS can directly regulate the function of Src function, and thus indirectly control
223
many cellular processes. Yet how Src responds to this regulation has remained elusive.
The URI scientists took a systematic approach, examined all the potential mechanisms, and
identified the sensor that enables Src to respond to ROS regulation. They further found that
the sensor is also present in several other similar enzymes, mostly in the FGFR family.
"Our results were surprising at first, given that the results contradict some reports in the
literature," Kemble said. "But there was always a very clear answer to each question we asked.
It was both unusual and exciting to see things progress as smoothly as it did."
According to Sun, this mechanism of regulation represents just a small piece of the large
puzzle of how Src is controlled in the cells. "Src function is under the control of several different
mechanisms; each one needs to fit in with the others to form a seamless regulatory system."
Sun said.
Notes:
The URI scientists next plan to study how these pieces fit together to control Src function in the
cells.
Source:
Todd McLeish
University of Rhode Island
3 月 28 日
Excellent Results Obtained In Head And Neck Tumors Using High
Dosage Brachytherapy
High-dosage perioperative brachytherapy (applied within the surgical process) obtains
excellent results in the treatment of head and neck tumours, at the same time as reducing the
period of radiation. These are the conclusions of research undertaken jointly by three
Departments at the University of Navarra Hospital and which was published in the latest issue
of Brachytherapy, official journal of the American Society of Brachytherapy.
The work describes the application of this new radiotherapy technique to 40 patients between
2000 and 2006. Given the size of the sample, the article is a description of the greatest
number of patients treated with high-dosage brachytherapy for head and neck tumours in
world medical literature. According to results, after a seven-year follow-up, the illness was
controlled in 86% of the cases and the percentage of survival was 52%.
In concrete, the research focused on the treatment of tumours in the oral cavity, those affecting
the tongue and the floor of the mouth, and those in the oropharyngeal region, such as tumours
of the tonsils.
Involved in the study was a multidisciplinary team of seven specialists from three departments
at the University of Navarra Hospital: the Radiotherapy Department, the Department of Oral
224
and Maxillofacial Surgery and the Ear, Nose and Throat Department.
Intensifying radiation dosage
As is known, brachytherapy is a radiotherapy treatment involving the placing of radioactive
sources within the tumour or nearby.
In the case in hand, the work analysed the application of brachytherapy as complementary
post-surgery treatment,
explained
Doctor
Rafael
Martínez-Monge,
Director
of
the
Radiotherapy Department. Some cases of head and neck tumours require the application of
radiotherapy after the surgical operation. Using this technique, they have managed to intensify
the radiation dosage with the goal of reducing relapse rates.
In certain treatments, brachytherapy provides better end-result possibilities than conventional
radiotherapy. The procedure enables the administration of doses that would not be easily
achieved using other techniques, due to toxic effects, explained the specialist from the
University of Navarra Hospital.
Two weeks of treatment less
Moreover, the use in brachytherapy of high dosages involves a series of benefits for the patient
as regards the overall treatment. The great advantage, points out Doctor Martínez-Monge, is
the reduction of total time. While conventional radiotherapy treatment lasted seven weeks,
administering part of the radiation through brachytherapy can take two weeks less.
This technique also manages to reduce the time of radiation compared to treatment with low
dosage brachytherapy. Thanks to the existence of new sources of radiation, the treatment is
released in a matter of minutes. Before the patient under brachytherapy treatment carried the
radioactive source for several days and, thus, had to be isolated in a lead-lined room, with
limitations on visits and nursing care. With high-dosage brachytherapy, however, the patient is
only radioactive during the actual administration of the treatment; as such, the rest of the time
can be spent in a conventional room.
For the administration of this technique it is necessary to prepare the affected region during the
surgical operation. On extirpating the tumour, the surgeon covers the surgery zone - the area
with greatest possibilities for relapse - with a series of plastic tubes which are subsequently
filled with radioactive material, the aim being to effect a highly selective and precise radiation.
Brachytherapy is introduced through these tubes, one end of which appears at the surface of
the skin, like a drainpipe, explained Doctor Rafael Martínez-Monge. These tubes are
connected to a machine that administers the treatment according to a computer programme
personalised for each patient, he added.
Application to other types of tumour
225
Apart from perioperative high-dosage brachytherapy treatment for head and neck tumours, the
University of Navarra Hospital has been working on the application of this procedure to other
oncological processes for a number of years. There are a number of studies under way on its
use in gynaecological tumours and sarcomas, amongst others. Since 2000 about 400 patients,
with different types of tumours, have been treated with this technique.
Source:
Oihane Lakar
Elhuyar Fundazioa
3 月 28 日
Graduate Program In Cancer Metastasis Launched By M. D. Anderson
A one-of-a-kind graduate program that focuses on the most lethal aspect of cancer will open
this fall at The University of Texas M. D. Anderson Cancer Center with support from a highly
competitive grant from The University of Texas System.
The Graduate Program in Cancer Metastasis Research: Bench to Bedside, will concentrate on
understanding and attacking the spread of cancer from its original site to other organs. The
program will be offered through The University of Texas Graduate School of Biomedical
Sciences at Houston, a combined program of M. D. Anderson and The University of Texas
Health Science Center at Houston.
"Metastasis is far and away the major killer of cancer patients, and this doctoral program is the
first to treat the study of metastasis as a separate discipline," said program organizer Gary E.
Gallick, Ph.D., professor and director of education in M. D. Anderson's Department of
Genitourinary Medical Oncology and a member of the GSBS faculty.
UT System allocated $485,250 to the metastasis program over three years, one of only seven
grants awarded in a systemwide competition called the Graduate Program Initiative. The
University of Texas System Board of Regents allocated $5 million for the initiative to cultivate
innovative programs that will attract high-quality graduate students to UT System institutions.
Each institution submitted multiple proposals.
"It's crucial that we improve our basic understanding of the underlying mechanisms for the
spread of cancer to distant sites," said M. D. Anderson Provost and Executive Vice President
Raymond DuBois, M.D. Ph.D. "This program will enhance the training of future scientists who
will advance metastasis research."
The metastasis program integrates a traditional hypothesis-driven, basic-science research
approach with M. D. Anderson's strong emphasis on cultivating close collaborations among
physicians and scientists. "Students will learn to appreciate the clinical aspects of metastasis
by visiting clinics and hearing physicians' perspectives on how the basic science issues
worked on by students play out in the clinic," Gallick said.
226
Many institutions have established interdisciplinary research programs in cancer biology that
include metastasis research. The organizers of the M. D. Anderson cancer metastasis
program have tailored new courses and approaches to address unique requirements of
metastasis research, providing students an unparalleled educational opportunity. The only
similar program is offered jointly by the Université de Lausanne in Switzerland in conjunction
with the Ludwig Institute for Cancer Research.
Top students admitted to the program will be designated I.J. Fidler Fellows in Metastasis
Research. The awards honor Isaiah J. Fidler, D.V.M., Ph.D., director of M. D. Anderson's
Cancer Metastasis Research Center and professor and former chair of the Department of
Cancer Biology, a longstanding leader in research and translational programs in the area of
metastasis whose pioneering work led to the recognition that metastasis is a separate
discipline of cancer biology, providing the basis for this new program.
Notes:
The GSBS is a combined program of M. D. Anderson and The University of Texas Health
Science Center at Houston.
Source:
Scott Merville
University of Texas M. D. Anderson Cancer Center
3 月 29 日
Endocyte Announces Positive Interim Results From
Phase II Clinical Trial Of EC145 In Patients With
Advanced Non-Small Cell Lung Cancer (NSCLC)
Endocyte Inc. has announced positive interim results from an ongoing Phase II clinical study of
EC145 in patients with advanced non-small cell lung cancer (NSCLC). The single arm Phase II
study is designed to evaluate treatment with EC145 in patients with chemotherapy-resistant
NSCLC who have failed multiple therapy regimens.
At the planned interim analysis, 35 percent (6/17) of patients achieved clinical benefit
(CR+PR+SD), 67 percent (4/6) of patients had a duration of response of six months or longer,
and one patient had significant tumor reduction (>30 percent). All of these patients had
previously failed two to eight prior therapies. Analysis of the safety data indicates that EC145
was generally well tolerated. Based on the positive results from the interim analysis, the
two-stage clinical trial will continue on to full enrollment.
EC145 links a very potent anticancer drug to the vitamin folate, which is required for cell
division. Rapidly dividing cancer cells over-express folate receptors to capture enough folate to
227
support cell division. By combining a chemotherapy drug with folate, EC145 targets cancer
cells while avoiding normal cells. This targeted approach is designed to reduce the risk of
toxicity and side effects often associated with the use of potent chemotherapy drugs. Endocyte
is also conducting a second Phase II clinical trial with EC145 and EC20, Endocyte's molecular
imaging agent. This randomized trial is known as the PRECEDENT study, and is evaluating
treatment with EC145 in patients with ovarian cancer.
Wael Harb, M.D., of the Care Group, Horizon Oncology Center, and investigator of the NSCLC
study, said, "I continue to be impressed by the way advanced lung cancer patients have
responded to EC145 treatment. These results include both prolonged responses and excellent
tolerability among patients who in the past failed multiple chemotherapy regimens."
Patients enrolled in the NSCLC study were also treated with EC20, which works to identify
tumors that over-express the folate receptor. EC20 is being developed to help clinicians
identify those patients most likely to respond to treatment with Endocyte's folate-targeted
therapeutics (such as EC145, EC0225, EC0489, etc).
"We are extremely pleased that these interim results support the continued development of
both EC145 and EC20 while further validating Endocyte's Drug Guidance System technology
platform. The ability to identify patients who are most likely to respond to a chemotherapy drug
and then deliver that drug with maximum precision will represent a major advance in patient
care," said Ron Ellis, Endocyte's president and CEO.
About Endocyte
Endocyte is a privately-held biotechnology company with headquarters in the Purdue
Research Park of West Lafayette, IN. Based on the applications of Endocyte's advanced
proprietary Drug Guidance System (DGS), the company is working to develop new drugs and
diagnostic agents to treat many types of cancer and other serious diseases. The DGS platform
makes it possible to use highly-potent drugs on extended and frequent dosing schedules and
in combination with other drugs to maximize efficacy. The technology improves drug targeting
and reduces the risk of side effects by combining drugs with ligands that are able to identify
and attach to receptors found on tumors and other disease cells. Endocyte is currently
conducting three separate Phase 2 clinical trials for its lead compound, EC145, together with
EC20, a companion molecular imaging agent, for the treatment of ovarian cancer and
non-small cell lung cancer. Other clinical-stage products in the Endocyte pipeline include:
EC0225, a combination of two potent anticancer drugs; BMS493, a potent drug being
developed in partnership with Bristol-Myers Squibb; EC17, a targeted immunotherapy agent;
and EC0489, a targeted cancer drug. The company also has multiple product candidates in
pre-clinical stage development.
This press release contains "forward-looking statements" as that term is defined in the Private
Securities Litigation Reform Act of 1995. These statements are based on management's
current expectations and involve significant risks and uncertainties that may cause results to
228
differ materially from those set forth in the statements. We undertake no obligation to publicly
update any forward-looking statement, whether as a result of new information, future events,
or otherwise.
Source
Endocyte
3 月 29 日
Bowel Cancer Screening Should Start At 25 For High
Risk Groups
Scientists at The Institute of Cancer Research (ICR) have discovered that a genetic marker
can detect whether relatives of bowel cancer patients are 20 times more likely to develop the
disease than the general population. The research suggests these high risk people should be
screened from the age of 25. The study is published today in the Journal of Clinical Oncology*.
The study, funded by Cancer Research UK, looked at 2,941 people with bowel cancer** to see
whether they carried bowel cancer genetic risk markers, using a test for microsatellite
instablility (MSI)*** which establishes if the genetic self-repair system is damaged allowing
cancer causing genetic mistakes to happen. They also asked the patients if their first degree
relatives - parents, siblings or children - had bowel cancer and at what age they were
diagnosed.
They discovered that if the tumours of a bowel cancer patient were MSI-positive and they were
diagnosed at a young age, then their first degree relatives were up to twenty times more likely
to develop the disease before the age of 70 compared with the general population. Of the
2,941 patients on the study 344 were found to be MSI-positive - 11.7 per cent. The risks for
relatives of MSI-negative patients were modest.
The researchers hope that doctors can use these findings to better calculate the risks of bowel
cancer for this high risk group and decide on appropriate screening. This will help them catch
the disease early, when treatment is more likely to be successful. It may also help prevent the
disease from developing in some patients if they can detect pre-cancerous polyps and remove
them before they become cancerous.
Professor Richard Houlston, lead investigator at the ICR, said: "Screening programmes can be
better tailored to individuals if information on the number of additional first degree relatives with
bowel cancer is used in conjunction with information on MSI status.
"We suggest from these results that screening from the age of 25, is recommended for first
degree relatives of bowel cancer patients whose tumour is positive for this genetic marker especially if there are one or more other members of the family with the disease.
229
"We also think that doctors can delay screening first degree relatives of patients who were
diagnosed before the age of 45 and who are MSI-negative for this genetic risk marker."
Scientists already knew that first degree relatives of bowel cancer patients have a two-fold
increased risk compared with the general public before the age of 70.
But the researchers deduced that if bowel cancer patients were additionally found to be
MSI-positive, the risk of relatives developing the disease before the age of 70 increased to
around four-fold that of the general population.
Additionally if bowel cancer patients were diagnosed at a young age - below 45 - then the risk
of their first degree relatives developing bowel cancer before the age of 70 was around six-fold
that of the general population. Furthermore, if bowel cancer patients were diagnosed young
and were also found to be MSI-positive, then the risk to close relatives of developing bowel
cancer increased to about twenty-fold.
Dr Lesley Walker, Cancer Research UK's Director of Cancer Information, said: "This important
research provides an accurate way to plan screening for the early detection of bowel cancer in
high-risk families."
"Bowel cancer is one of the UK's most common cancers and although three quarters of cases
are found in people over the age of 65, we know that people with a first degree relative with the
disease are at higher than average risk. Anything which helps us to further assess the level of
risk means we can target measures aimed at preventing the cancer or detecting it early to
those with greatest need."
*Implications of familial colorectal cancer risk profiles and MSI status. Steven J Lubbe
et al. Journal of Clinical Oncology 2009.
**Bowel Cancer
Each year more than 36,500 people are diagnosed with bowel cancer in the UK, that's 100
people every day. In 2006 there were 15,957 deaths from colorectal cancer in the UK,
comprising 10,119 from colon and 5,838 from rectal cancer
Bowel cancer is the third most common cancer in the UK and the second greatest cause of
cancer death in the UK.
*** Microsatellites
Faults in genes can occur every time cells divide and DNA is replicated. The genes which
correct these faults are called mismatch repair (MMR) genes. But mistakes can't be corrected
if there is a mutation in any one of these MMR genes.
230
If mistakes lie within genes that are vital for cell function, then cells will grow abnormally and
form a tumour.
Microsatellites are chromosome regions particularly prone to errors during replication. A
normal mismatch repair system will correct these errors and retain the original DNA sequence.
However, a faulty mismatch repair system will not correct these errors, and accumulate and
produce many variations in a genetic sequence as cells replicate, mutate and divide.
This is termed "microsatellite instability" (MSI) and is a sign that the mismatch repair pathway
is not functioning correctly.
****In England, the NHS Bowel Cancer Screening Programme will be rolled out in all areas by
the end of 2009. Men and women aged between 60 and 69 years old are sent a stool testing
kit every 2 years. People aged 70 and over can request a kit. From 2010, people aged 70 to 75
will also be included in the screening programme.
The national bowel screening programme in Scotland started in June 2007 to be rolled out
across the whole country over two years. Men and women aged between 50 and 74 years are
sent a stool testing kit every 2 years.
In Wales the NHS plans to test people between the ages of 50 and 74 every two years. Men
and women aged between 60 and 69 from October 2008 receive stool testing kits. The NHS
hopes to have rolled the service out to everyone else in the target age group by 2015.
In Northern Ireland the NHS plans to start screening in 2009.
Funding
This research has been funded by Cancer Research UK, the ICR, CORE, the European
Commission and St. George's Hospital, London.
The Institute of Cancer Research
The Institute of Cancer Research is Europe's leading cancer research centre with expert
scientists working on cutting edge research. In 2009, The ICR marks its 100 years of world
leading research into cancer prevention, diagnosis and treatment.
Scientists at the ICR have identified more cancer related genes than any other organisation in
world. These discoveries are allowing for scientists to develop new cancer treatments. The
ICR is a charity that relies on voluntary income. It is one of the world's most cost-effective
major cancer research organisations with more than 95p in every £ directly supporting
research. For more information visit http://www.icr.ac.uk.
Cancer Research UK
231
- Cancer Research UK's vision is to conquer cancer through world-class research.
- The charity works alone and in partnership with others to carry out research into the biology
and causes of cancer, to develop effective treatments, improve the quality of life for cancer
patients, and reduce the number of people getting cancer and to provide authoritative
information on cancer. Cancer Research UK is the world's leading independent charity
dedicated to research on the causes, treatment and prevention of cancer.
- For further information about Cancer Research UK's work or to find out how to support the
charity, please call 020 7009 8820 or visit http://www.cancerresearchuk.org
Source
Cancer Research UK
3 月 30 日
Multiple sclerosis associated with lower cancer risk
ST. PAUL, Minn. – A new study shows that people with multiple sclerosis may be at a lower
risk for cancer overall, but at a higher risk of developing certain types of cancer, such as brain
tumors and bladder cancer. The study is published in the March 31, 2009, print issue of
Neurology®, the medical journal of the American Academy of Neurology.
Researchers looked at the medical records of 20,000 people with multiple sclerosis and
204,000 people without the diagnosis. After 35 years, they found that the people with MS had
a decreased overall risk of cancer by 10 percent compared to people who did not have the
disease. The result was more pronounced in women. However, for people with MS the risk for
certain cancers, such as brain tumors and bladder and other urinary organ cancers, increased
by up to 44 percent compared to people without MS.
Scientists also evaluated the parents of people with MS to determine whether there was a
possible genetic link. They found that there was no overall increased or decreased risk of
cancer among either mothers or fathers of those with MS, compared to parents of people
without MS.
"We speculate that the lower risk for cancer among people with MS could be a result of
lifestyle changes or treatment following diagnosis," said study author Shahram Bahmanyar,
MD, PhD, of the Karolinska Institute in Sweden. "The increase in brain tumor diagnoses may
be due to brain inflammation, but this finding may not reflect a real increase in cancer risk, as
there is some evidence that more frequent neurological investigations in these patients mean
that brain tumors are more likely to be found sooner. There may also be reasons related to
the disease that could increase the risk for urinary organ cancers, resulting from chronic
irritation to those organs as a result of MS. However, individual risk of developing urinary
232
organ cancer is modest, as less than 0.2 percent of people with MS developed this cancer for
every 10 years of follow-up."
Bahmanyar also noted that people with MS have on average a lower body mass index (BMI)
than the general population, and BMI is a risk factor for several types of cancer, so the lower
body weight may explain some of the reduction in cancer risk. It is also possible that some
reduction in cancer risk results from the way the body responds to MS.
###
The study was supported by the Bibbi and Nils Jensens Foundation, the Montel Williams
Foundation, the European Union's Sixth Framework Program NeuroproMiSe and the Swedish
Association for Persons with Neurological Disabilities.
The American Academy of Neurology, an association of more than 21,000 neurologists and
neuroscience professionals, is dedicated to improving patient care through education and
research. A neurologist is a doctor with specialized training in diagnosing, treating and
managing disorders of the brain and nervous system such as multiple sclerosis, restless legs
syndrome, Alzheimer's disease, narcolepsy, and stroke.
For more information about the American Academy of Neurology, visit www.aan.com.
3 月 30 日
Angiogenesis inhibitor improves brain tumor survival
by reducing edema
Mice treated with experimental drug cediranib live longer despite continued tumor
growth
The beneficial effects of anti-angiogenesis drugs in the treatment of the
deadly brain tumors called glioblastomas appear to result primarily from
reduction of edema – the swelling of brain tissue – and not from any
direct anti-tumor effect, according to a study from Massachusetts General
Hospital (MGH) researchers. Their report, to be published in the Journal
of Clinical Oncology and receiving early online release, describes how
treatment with the experimental drug cediranib reduced edema and improved
survival in three mouse models of glioblastoma.
"Our findings suggest that antiangiogenesis therapy can increase patient
survival even in the face of persistent tumor growth," says Rakesh K. Jain,
PhD, director of the Steele Laboratory in the MGH Department of Radiation
233
Oncology, the study's co-senior author. "In glioblastoma clinical trials,
it is important to separate survival analysis from that of tumor response
to therapy, since many factors combine to cause patient deaths."
Cediranib inhibits the potent angiogenesis factor VEGF, which is known
to be abundantly present in glioblastomas and play a critical role in tumor
blood vessel formation. A 2007 report from an ongoing clinical trial at
the MGH Cancer Center found that the drug temporarily normalized abnormal,
leaky blood vessels in glioblastomas that had recurred after surgery,
radiation or chemotherapy – reducing edema and apparently the size of
the tumors. But the exact mechanism underlying the effects was unclear,
since the imaging technology used to track tumor progression could not
distinguish between effects on blood vessels and an actual reduction in
tumor size.
"We frequently see beneficial effects from drugs in patients without fully
understanding the mechanism of action," says A. Gregory Sorensen, MD, of
the MGH Radiology Department and Martinos Center for Biomedical Imaging,
co-senior author of the report.. "The fact that anti-VEGF agents seem to
provide clear benefits in some glioblastoma patients adds to the urgency
of understanding the mechanisms that underlie these clinical improvements.
We need to learn how to tailor our treatments to benefit even more
patients."
The current study was designed to clarify whether cediranib's clinical
effects primarily resulted from reduction of edema, which has significant
consequences within the brain, or from a direct anti-tumor effect. The
researchers implanted fluorescently labeled human or rat glioblastoma
cells into the brains of mice and directly observed the tumors and
surrounding tissue through transparent windows through the skull. Once
tumors began growing, some of the mice received daily doses of cediranib,
along with daily measurement of tumor growth, edema and of blood vessel
structure and function.
Mice treated with cediranib were found to have significant reductions in
the size and permeability of tumor-associated blood vessels, compared
with animals that did not receive the drug. Although treatment did not
reduce the rate of tumor growth, mice receiving cediranib lived
significantly longer than the control animals. Another group of
tumor-bearing mice received the steroid drug most commonly used to treat
edema, and though those animals also lived longer than controls, the
survival benefit was greater for the mice receiving cediranib.
"This is the first paper to show that vascular normalization alone,
without chemotherapy, can be effective against some tumors by controlling
234
edema and that this anti-edema effect is better than that of currently
used steroids," Jain says. "Unfortunately, these anti-VEGF agents did not
slow the tumor growth rate in these models; and since recurrent
glioblastomas are highly resistant to currently used chemotherapy drugs,
even if vascular normalization increases drug delivery, there may be
little or no additional increase in patient survival. We urgently need
to find better anti-tumor and anti-angiogenic agents."
Study co-author Tracy Batchelor, MD, director of the Pappas Center for
Neuro-Oncology at MGH, notes, “This is an animal study involving a drug
that is in ongoing phase 2 and 3 human trials here at MGH and elsewhere.
We have already completed a phase 2 trial in glioblastoma patients that
had very promising results, and the only way to definitively determine
how cediranib and similar agents are helping patients with glioblastoma
will be for more patients to participate in and complete these trials.”
Jain adds that it will be important to identify biomarkers that may
indicate which patients are most likely to benefit from treatment with
angiogenesis inhibitors and to identify the mechanisms by which
glioblastomas and other tumors resist anti-VEGF therapies. Jain is the
Cook Professor of Tumor Biology and Sorensen is an associate professor
of Radiology at Harvard Medical School.
###
Walid Kamoun, PhD, and Carsten D. Ley, PhD, of the Steele Laboratory and
Christian Farrar, PhD, Martinos Center for Biomedical Imaging – all at
MGH – are co-lead authors of the Journal of Clinical Oncology paper.
Additional co-authors are Annique Duyverman, MD, Johanna Lahdenranta, PhD,
Delphine Lacorre, PhD, Emmanuelle di Tomasso, PhD, Dan G. Duda, PhD, DMD,
Lance L. Munn, PhD, and Dai Fukumura, MD, PhD, of the Steele Lab. The study
was supported by grants from the National Institutes of Health, the Susan
G. Komen Foundation, the Damon Runyon Foundation, the U.S. Department of
Defense, the Montesi Family Research Fund and AstraZeneca Pharmaceuticals,
which manufacturers cediranib under the brand name RECENTIN.
Massachusetts General Hospital, established in 1811, is the original and
largest teaching hospital of Harvard Medical School. The MGH conducts the
largest hospital-based research program in the United States, with an
annual research budget of more than $500 million and major research
centers in AIDS, cardiovascular research, cancer, computational and
integrative biology, cutaneous biology, human genetics, medical imaging,
neurodegenerative disorders, regenerative medicine, systems biology,
transplantation biology and photomedicine.
235
3 月 30 日
Translational Research Identifies Marker Pointing Way To First Test For Breast
Cancer Metastasis, NewYork-Presbyterian/Weill Cornell
Researchers at NewYork-Presbyterian Hospital/Weill Cornell Medical Center have identified a
new marker for breast cancer metastasis called TMEM, for Tumor Microenvironment of
Metastasis. As reported in the March 24 online edition of the journal Clinical Cancer Research,
density of TMEM was associated with the development of distant organ metastasis via the
bloodstream -- the most common cause of death from breast cancer.
The National Cancer Institute (NCI)-funded translational study could lead to the first test to
predict the likelihood of breast cancer metastasis via the bloodstream -- a development that
could change the way breast cancer is treated.
An estimated 40 percent of breast cancer patients relapse and develop metastatic disease.
About 40,000 women die of metastatic breast cancer every year.
"Currently, anyone with a breast cancer diagnosis fears the worst -- that the cancer will spread
and threaten their lives. A tissue test for metastatic risk could alleviate those worries, and
prevent toxic and costly measures like radiation and chemotherapy," says senior author Dr.
Joan G. Jones, professor of clinical pathology and laboratory medicine at Weill Cornell Medical
College and director of Anatomic Pathology at NewYork-Presbyterian Hospital/Weill Cornell
Medical Center.
"If patients can be better classified as either low risk or high risk for metastasis, therapies can
be custom tailored to patients, preventing over-treatment or under-treatment of the disease,"
adds
first
author
Dr.
Brian
D.
Robinson,
resident
in
Anatomic
Pathology
at
NewYork-Presbyterian Hospital/Weill Cornell Medical Center.
The Weill Cornell investigators set out to build on previous research by co-author Dr. John S.
Condeelis of the Albert Einstein College of Medicine. Working in animal models, he identified a
link between blood-borne or systemic metastasis and a three-part association between
invasive carcinoma cells, perivascular white blood cells (macrophages) and the endothelial
cells that line vessel walls. To confirm this finding in humans, Drs. Jones and Robinson
developed a triple immunostain for human breast cancer samples that simultaneously labels
the three cell types that together they named TMEM (Tumor Microenvironment of Metastasis).
In a case-control study, they performed a retrospective analysis of tissue samples from 30
patients with invasive ductal carcinoma of the breast who developed systemic, distant-organ
metastases. These samples were compared to matched controls that had only localized
disease (i.e., invasive ductal carcinoma limited to the breast or with regional lymph node
metastasis only). All patients were female and underwent primary resection of their breast
cancer at NewYork-Presbyterian Hospital/Weill Cornell Medical Center between 1992 and
2003.
236
They found that TMEM density was more than double in the group of patients who developed
systemic metastases compared with the patients with only localized breast cancer (median of
105 vs. 50, respectively). Offering further evidence in support of the TMEM concept, they
found that in well-differentiated tumors, where the outcome is generally good, the TMEM count
was low.
Notably, TMEM density was associated with the development of distant-organ metastasis,
independent of lymph node status and tumor grade.
"Traditionally, the likelihood of breast cancer metastasis is estimated based on tumor size,
tumor differentiation -- how similar or dissimilar the tumor is compared to normal breast tissue
-- and whether it has spread to the lymph nodes. While these are useful measures, TMEM
density directly reflects the blood-borne mechanism of metastasis, and therefore may prove to
be more specific and directly relevant," says Dr. Jones.
The researchers say the next step will be to validate the findings in a larger sample group. Also
on the agenda is identifying a threshold TMEM density for metastasis risk, and streamlining
the process for measuring TMEM.
Breast cancer is the most prevalent malignant disease of women in the developed world, apart
from non-melanoma skin cancers, with approximately one in eight women in the United States
being diagnosed with breast cancer at some time in their lives. While an estimated 10 percent
to 15 percent of patients have an aggressive form of the disease that metastasizes within three
years after initial diagnosis, metastasis can take 10 years or longer to occur. To decrease the
risk for the emergence of metastatic tumors, approximately 80 percent of breast cancer
patients are treated with adjuvant chemotherapy. The clinical benefit is a 3 percent to 10
percent increase in 15-year survival, depending upon the age of the patient at diagnosis.
Study co-authors include Drs. Gabriel L. Sica and Yi-Fang Liu of NewYork-Presbyterian/Weill
Cornell; Dr. Thomas E. Rohan of the Department of Epidemiology and Population Health at
Albert Einstein College of Medicine; Dr. Frank B. Gertler of the Department of Biology, Koch
Institute for Integrative Cancer Biology at Massachusetts Institute of Technology; and Dr. John
S. Condeelis of the Department of Anatomy & Structural Biology, Program in Tumor
Microenvironment and Metastasis, Albert Einstein Cancer Center at the Albert Einstein College
of Medicine.
The study was funded by the Integrative Cancer Biology Program (ICBP) of the National
Cancer Institute (NCI).
NewYork-Presbyterian Hospital/Weill Cornell Medical Center
NewYork-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one
of the leading academic medical centers in the world, comprising the teaching hospital
NewYork-Presbyterian and Weill Cornell Medical College, the medical school of Cornell
237
University. NewYork-Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory
and preventive care in all areas of medicine, and is committed to excellence in patient care,
education, research and community service. Weill Cornell physician-scientists have been
responsible for many medical advances -- from the development of the Pap test for cervical
cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in
the U.S., the first clinical trial for gene therapy for Parkinson's disease, the first indication of
bone marrow's critical role in tumor growth, and, most recently, the world's first successful use
of
deep
brain
stimulation
to
treat
a
minimally
conscious
brain-injured
patient.
NewYork-Presbyterian, which is ranked sixth on the U.S.News & World Report list of top
hospitals, also comprises NewYork-Presbyterian Hospital/Columbia University Medical Center,
Morgan Stanley Children's Hospital of NewYork-Presbyterian, NewYork-Presbyterian
Hospital/Westchester Division and NewYork-Presbyterian Hospital/The Allen Pavilion. Weill
Cornell Medical College is the first U.S. medical college to offer a medical degree overseas
and maintains a strong global presence in Austria, Brazil, Haiti, Tanzania, Turkey and Qatar.
Source
NewYork-Presbyterian Hospital/Weill Cornell Medical Center
3 月 30 日
Breast Cancer In A Test Tube Wins Prize For Replacing
Laboratory Animals
British scientists who developed an advanced three dimensional (3-D) model of human breast
cancer in the test tube, have won a prestigious prize for replacing animal experiments in
medical research. The award was made at an event at the House of Lords sponsored by
former Minister for Science & Innovation Lord Sainsbury and hosted by the National Centre for
the Replacement, Refinement and Reduction of Animals in Research (NC3Rs).
The research, which was published in Breast Cancer Research journal [1] was funded by the
Dr Hadwen Trust for Humane Research charity which pioneers new techniques to replace
animals in medical experiments [2].
Dr Deborah Holliday [3], now based at the Department of Pathology and Tumour Biology,
Leeds Institute of Molecular Medicine, and colleagues from Queen Mary's, University of
London, have constructed a multi-cellular 3-D model of ductal carcinoma in situ (DCIS), a
pre-invasive lesion which is the main precursor to breast cancer and accounts for 20% of all
breast cancer. The highly successful, complex model useshuman cells from cancerous and
healthy breast tissue donated by volunteers and is set to help replaceexperiments using up to
400 mice per test typically involving implanting tumours, abdominal drug injections and serial
'harvesting' of tumours. [4]
Breast cancer is the most common cancer affecting women in the Western world. Over 45,000
women were diagnosed with breast cancer in the UK in 2005, around 125 women each day [5].
238
Research has been complicated by the fact that the animal 'models' used for cancer research
differ significantly from human cancer. More human-relevant research methods are
desperately needed to improve research quality.
The 3-D replacement model accurately replicates what happens at a cellular level in normal
and malignant human breast. Containing all the different cell types present in breast tissue, it is
physiologically relevant and capable of complex, functional studies including the identification
and screening of novel therapeutic targets. [6]
"Winning the NC3Rs prize is an important recognition of the quality of non-animal replacement
methods, and the scientific and ethical benefits of replacing animals in medical research." says
Wendy Higgins, Dr Hadwen Trust for Humane Research. "Supporting groundbreaking
non-animal medical research like this is vitally important because eliminating human and
animal suffering is a goal that benefits us all."
The development of a human-relevant model means that researchers can far more reliably
investigate the earlier stages of cancer, and its progression, as well as potential new breast
cancer treatments.
Dr Deborah Holliday [5] is convinced that non-animal solutions like the 3-D model, are the way
forward in breast cancer research.
Says Dr Holliday: "This is an exciting development in both breast cancer research and the
replacement of animals so I am thrilled at the award . Understanding how individual cell
populations contribute to cancer progression is essential in increasing our understanding of
breast cancer and identifying new targets for therapy. Being able to model this in a complex
human 3-D culture model provides us with a valuable tool to investigate this without the use of
animal experiments."
The event was hosted by the NC3Rs as part of its celebrations to mark the 50th anniversary of
Russell and Burch's concept of replacement, reduction and refinement of animal experiments
(3Rs). The poster event was held on Wednesday 25th March to demonstrate original 3Rs
research from the UK for MPs and Peers. Dr Holliday was awarded £3,000. [8]
Notes
1. Novel multicellular organotypic models of normal and malignant breast: tools for dissecting
the role of the microenvironment in breast cancer progression Deborah L Holliday, Kellie T
Brouilette, Anja Markert, Linda A Gordon, J Louise Jones. Breast Cancer Research 2009,
11:R3 (19 January 2009). http://breast-cancer-research.com/content/11/1/R3
2. The Dr Hadwen Trust is the UK's leading medical research charity funding exclusively
non-animal research techniques to replace animal experiments, benefiting people and animals.
http://www.drhadwentrust.org
239
3. Dr Deborah Holliday, Breast Research Group, Section of Pathology and Tumour Biology,
Leeds Institute of Molecular Medicine. Email: D.L.Holliday@leeds.ac.uk Tel: 0113 343 8624
4. In DCIS cells inside some of the ducts of the breast start to become cancerous but are at a
stage where they have not yet invaded the rest of the breast.
5. Statistics from Cancer Research UK.
6. Experiments so far with the 3-D model have shown that if the cells which surround invasive
tumours (called fibroblasts) are taken from cancer-containing breast tissue, they disrupt
structures, giving the cells a disorganised appearance often seen in cancer. However,
fibroblasts taken from healthy breast tissue don't cause this disruption.The team has also
shown that the 3-D model is accurate enough to establish which specific enzymes play a
prominent role in the propagation of tumour cells into healthy breast tissue.
7. Photos of the 3-D model (taken under the microscope) are available on request from the Dr
Hadwen Trust.
8. W.M.S. Russell and R.L. Burch (1959) The Principles of Humane Experimental Technique.
London, UK: Methuen
9. The NC3Rs was established in 2004 by the government http://www.nc3rs.org.uk
Source
Dr Hadwen Trust
3 月 31 日
GSK Appeals Against NICE Decision To Deny Women Advanced Breast
Cancer Treatment, Tyverb(R) (Lapatinib), UK
GlaxoSmithKline (GSK) confirmed that it is to appeal against the decision by NICE to deny
NHS funding for Tyverb® (lapatinib), a treatment for an aggressive form of advanced breast
cancer (ErbB2-positive).1 If successful the appeal will enable the NHS to offer a similar level of
access to lapatinib as other EU countries. Lapatinib received EMEA approval* in June 2008
and since then it has been granted funding in 16 European countries to date including
Slovenia, Slovakia, France, Spain, Germany, Italy and Ireland.
Lapatinib (in combination with Xeloda® [capecitebine]) is licensed* for a particular type of
aggressive breast cancer, known as ErbB2 positive.2 It is the only licensed* ErbB2 targeted
treatment for these patients. Lapatinib has been shown to significantly delay the progression of
the cancer, helping to control it in women whose disease returned despite treatment with
standard chemotherapies and Herceptin® (trastuzumab).2,3 For these women, who have very
few treatment options available, lapatinib offers a chance of precious, additional time without
their disease progressing.
240
Simon Jose, General Manager, GSK UK commented; "We recognise that NICE has some
tough funding decisions to make, but urge it to reconsider. GSK's NICE submission
demonstrated that Tyverb, in conjunction with the patient access programme, could actually
save the NHS money. We have appealed against the decision but will continue to offer the
patient access programme to individual NHS trusts to help ensure Tyverb is available to the
women who could benefit from it."
GSK will appeal the decision, which affects around 2,000 women a year, because it believes it
has demonstrated that lapatinib (plus capecitabine) in conjunction with the patient access
programme offers a clinically and cost effective new treatment option that meets a significant
clinical need. Although NICE acknowledged that lapatinib is an effective treatment for eligible
women, it was rejected on the grounds that it was not a cost effective use of NHS resources.
This decision which was reached despite GSK offering a patient access programme whereby
the cost of up to 12 weeks treatment would be paid by the company. Some local NHS Trusts
have recognised the benefits of the patient access programme and are already signing up to
the scheme.
GSK recognised in its NICE submission that lapatinib would not be cost effective versus
standard chemotherapy alone, which fewer than 50% of patients with ErbB2 positive breast
cancer receive in clinical practice. However NICE acknowledged that the majority of women
whose disease has progressed, despite treatment with trastuzumab, continue to receive
treatments containing trastuzumab (Herceptin®) and this is unlikely to be cost-effective. GSK's
analysis suggests that the cost effectiveness of lapatinib in the context of the patient access
programme (sensitive to the proportion of trastuzumab used in clinical practice) demonstrated
a cost per QALY gain for lapatinib of just over £16,000 versus the usual care given to these
patients, which includes standard chemotherapy and trastuzumab regimens.1
Dr Alison Jones, Medical Oncologist at the University College London Hospital and the Royal
Free Hospital added: "Lapatinib is a clinically effective treatment option specifically licensed for
these patients. It's frustrating to know that my colleagues in the US and Europe are able to use
lapatinib for these patients when I and other consultants can't."
Safety Information:
Lapatinib plus capecitabine is generally well tolerated. The most common adverse events
associated with lapatinib plus capecitabine were diarrhoea, rash, nausea, vomiting, fatigue
and hand-foot syndrome.2,3 Diarrhoea and rash were more common with the combination
whilst the incidence of hand-foot syndrome was similar between the two treatment groups.2 A
decrease in left ventricular ejection fraction (LVEF) was reported by 2.5% of patients receiving
lapatinib plus capecitabine vs. 1% of patients on capecitabine alone.2 Hepatobiliary events
(mainly raised liver enzymes and/or bilirubin levels) have been reported commonly in
association with lapatinib plus capecitabine therapy.2 Lapatinib has also been associated with
reports of pulmonary toxicity.2
241
About Tyverb
- * Tyverb received a conditional marketing authorisation in Europe, June 2008.2
- Tyverb, in combination with capecitabine, is indicated for the treatment of patients with
advanced or metastatic breast cancer whose tumours overexpress ErbB2 (HER2). Patients
should have progressive disease following prior therapy which must include anthracyclines
and taxanes and therapy with trastuzumab in the metastatic setting.2
- Healthcare professionals should refer to the Tyverb Summary of Characteristics (SPC) for full
prescribing information, including warnings and precautions.2
About the Tyverb Patient Access Programme
GSK proposed the patient access programme in the UK when NICE indicated early on in its
review that it did not consider lapatinib to be cost effective in treating this patient population. In
an effort to achieve a positive outcome for patients and greater value to the NHS, GSK bears
the cost of lapatinib, for all eligible patients under the scheme, for up to the first 12 weeks of
treatment. The NHS would commence payment only for the patients who continue to receive
clinical benefit beyond 12 weeks. GSK will continue to honour the patient access programme
for NHS trusts in the UK.
GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare
companies - is committed to improving the quality of human life by enabling people to do more,
feel better and live longer. For further information please visit http://www.gsk.com
Tyverb® is a registered trademark of the GlaxoSmithKline group of companies. Herceptin®
and Xeloda® are registered trademarks of F. Hoffmann-La Roche.
References
1. Lapatinib for the treatment of women with previously treated advanced or metastatic breast
cancer.
Final
appraisal
determination,
5
http://www.nice.org.uk/guidance/index.jsp?action=download&o=43476
March
Last
2009
accessed
26
March 2009
2.
Tyverb®
(lapatinib)
Summary
of
Product
Characteristics.
http://emc.medicines.org.uk/medicine/20929/SPC/Tyverb Last accessed 26 March 2009
3. Cameron D, Casey M, Press M, et al. A phase III randomised comparison of lapatinib plus
capecitabine versus capecitabine alone in women with advanced breast cancer that has
progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res
Treat 2008; 112:533-543
242
Source
GlaxoSmithKline
View drug information on Herceptin; Xeloda.
3 月 31 日
Helping To Diagnose Skin Cancer Without A Biopsy
A recent Montana State University master's graduate is working with doctors at Vanderbilt
Medical Center in Tennessee to build a handheld laser microscope that could someday reduce
the number of biopsies needed to diagnose skin cancer.
Suspicious spots on the skin often prompt dermatologists to remove skin samples for analysis.
These procedures are currently the best way to diagnose skin cancers, said Chris Arrasmith,
who recently earned his master's degree and now works as a researcher in MSU's electrical
engineering department.
But biopsies are invasive procedures that are often painful. Millions are conducted each year
in the United States, and according to the American Cancer Society, most of those biopsies -as many as 80 percent for some types of cancers -- come back negative.
The handheld microscope could help doctors get a better idea when biopsies are absolutely
necessary. That would cut down on the number of biopsies that have to be performed and
streamline the process of diagnosing cancers, Arrasmith said.
"Any combination of tools we can provide to enable early detection of any kind of disease is a
good thing," said Arrasmith, 25.
Like most microscopes, the MSU-Vanderbilt device uses lenses to look at a patient's skin, but
instead of illuminating the skin with normal white light, the device uses laser light.
The laser light is used to form an image of the skin's cellular structure, and it monitors the way
a patient's cells change the reflected laser light, Arrasmith said. Those changes to the light can
tell scientists the chemical composition of the skin cells -- a process called spectroscopy.
"Within the microscope's image, we can select an area of interest, and from that we can take a
spectrum and get chemical data," Arrasmith said.
Doctors would then compare that chemical signature to a database containing the chemical
signatures of known cancers to see whether the patient's cells are cancerous.
The project, which Arrasmith began working on when he was an undergraduate at MSU, is
funded by a five-year grant from the National Institute of Biomedical Imaging and
Bioengineering, part of the National Institutes of Health. The NIBIB focuses on researching
243
new biomedical imaging devices and techniques to improve the detection, treatment and
prevention of disease.
The $1.79 million grant is administered by Vanderbilt. MSU will receive $500,000 from the
grant over all five years. That money covered, among other things, the cost of the microscope
itself and Arrasmith's graduate tuition.
David Dickensheets, an associate professor of electrical and computer engineering at MSU
and adviser to Arrasmith's work, said other labs have built microscopes that work on the same
principles, but they have been desktop instruments that still required skin samples to be taken
from patients.
Shrinking the microscope takes advantage of MSU's expertise in a field called
micro-electrical-mechanical systems, or MEMS.
The handheld microscope contains a tiny mirror made of silicon that scans the laser beam
across the skin, Dickensheets said. This allows the microscope to form an image and lets it
look at cells beneath the patient's outer skin layer.
Merging MSU's expertise in microscopy and MEMS with Vanderbilt's spectroscopy research
will produce a device that could one day find its way into dermatology clinics around the world,
Dickensheets said.
"We think that microscopic imaging of cell structure combined with the chemical specificity
provided by spectroscopy is the real key to making it a useful tool," Dickensheets said.
For Arrasmith, who has worked on the microscope since 2006, the approaching end of his time
at MSU is both satisfying and bittersweet.
It's satisfying, he said, because he's been able to build a prototype microscope that's now
being tested at Vanderbilt's medical clinics. It's bittersweet, he said, because he knows he
won't be around to see the finished second-generation model, which he hopes will be about
the size of a chalkboard eraser.
"As a person who likes to see things from start to completion, it's difficult to leave in the middle
of a long project like this," he said.
But he said the experience he's gained from having a hand in every aspect of the project -from theory and design to machining parts -- will give him a leg up in searching for an
engineering job after he leaves MSU.
"This project has really allowed me to see how things come together from multiple facets of
design," he said. "What I'm taking away from MSU is a general knowledge base that I can
apply to any other situation."
244
Source:
Michael Becker
Montana State University
3 月 31 日
Celsion Receives Orphan Drug Designation For ThermoDox(R) To Treat
Primary Liver Cancer
Celsion Corporation (NASDAQ:CLSN), a leading oncology drug development company,
announced that the U.S. Food and Drug Administration (FDA ) has granted orphan drug
designation for its lead compound, ThermoDox®, a proprietary heat-activated liposomal
encapsulation of doxorubicin, for the treatment of hepatocellular carcinoma (HCC), commonly
referred to as primary liver cancer. ThermoDox® is currently being evaluated under a Special
Protocol Assessment with the FDA in a 600 patient, global Phase III trial in patients with
non-resectable primary liver cancer. Celsion expects to complete patient enrollment for this
trial in the first quarter of 2010.
"We are pleased to receive FDA orphan drug designation for ThermoDox®," stated Mr.
Michael H. Tardugno, Celsion's President and Chief Executive Officer. "Orphan drug status is
an acknowledgement of the significant unmet need to develop a new treatment for patients
with primary liver cancer, a life threatening disorder for which today there is no effective
chemotherapeutic standard of care. We look forward to working with the FDA and other
regulatory agencies to make ThermoDox® available to patients as soon as possible."
FDA's Orphan Drug Act provides economic incentives to encourage biotechnology and
pharmaceutical companies to develop drugs that demonstrate promise for the treatment of
life-threatening or very serious conditions that are rare and affect 200,000 persons or less in
the United States. Orphan drug designation entitles Celsion to seven years of market
exclusivity following FDA approval, FDA assistance in clinical trial design, a reduction in FDA
user fees, U.S. tax credits related to development expenses as well as the opportunity to apply
for funding from the U.S. government to defray costs of clinical trial expenses.
Primary liver cancer is one of the most deadly forms of cancer and ranks as the fifth most
common solid tumor cancer. The incidence of primary liver cancer is approximately 20,000
cases per year in the United States and is rapidly growing worldwide at approximately
1,000,000 cases per year, due to the high prevalence of Hepatitis B and C in developing
countries. The standard first line treatment for liver cancer is surgical resection of the tumor,
however 80% to 90% of patients are ineligible for surgery. Radio frequency ablation (RFA) has
increasingly become the standard of care for non-resectable liver tumors, but the treatment
becomes less effective for larger tumors. There are few non-surgical therapeutic treatment
options available as radiation therapy and chemotherapy are largely ineffective in the
treatment of primary liver cancer.
About ThermoDox®
245
ThermoDox® in combination with hyperthermia has the potential to provide local tumor control
and improve quality of life. ThermoDox® is a proprietary heat-activated liposomal
encapsulation of doxorubicin, an approved and frequently used oncology drug for the
treatment of a wide range of cancers including breast cancer. Localized mild hyperthermia
(40-42 degrees Celsius) releases the entrapped doxorubicin from the liposome. This delivery
technology enables high concentrations of doxorubicin to be deposited preferentially in a
targeted tumor.
For primary liver cancer, ThermoDox® is being evaluated in a 600 patient global Phase III
study at 40 clinical sites under an FDA Special Protocol Assessment. The study is designed to
evaluate the efficacy of ThermoDox in combination with RFA when compared to patients who
receive RFA alone as the control. The primary endpoint for the study is progression-free
survival and enrollment is expected to be completed in the first quarter of 2010. For recurrent
chest wall breast cancer, ThermoDox® is being evaluated in a pivotal Phase I/II open-label,
dose-escalating trial that is designed to measure durable local complete response at the tumor
site. Celsion expects to enroll approximately 100 patients across the United States and to
complete the study by the first half of 2010. Additional information on these ThermoDox®
clinical studies may be found at http://www.clinicaltrials.gov.
About Celsion
Celsion is a leading oncology company dedicated to the development and commercialization
of innovative cancer drugs including tumor-targeting treatments using focused heat energy in
combination with heat-activated drug delivery systems. Celsion has research, license, or
commercialization agreements with leading institutions such as the National Institutes of
Health, Duke University Medical Center, University of Hong Kong, Cleveland Clinic, and the
North Shore Long Island Jewish Health System.
For more information on Celsion, visit our website: http://www.celsion.com.
Celsion wishes to inform readers that forward-looking statements in this release are made
pursuant to the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995.
Readers are cautioned that such forward-looking statements involve risks and uncertainties
including, without limitation, unforeseen changes in the course of research and development
activities and in clinical trials by others; possible acquisitions of other technologies, assets or
businesses; possible actions by customers, suppliers, competitors, regulatory authorities; and
other risks detailed from time to time in the Company's periodic reports filed with the Securities
and Exchange Commission.
Source
Celsion
3 月 31 日
246
Afinitor(R) Approved In US As First Treatment For Patients With
Advanced Kidney Cancer After Failure Of Either Sunitinib Or Sorafenib
Novartis announced that Afinitor(R) (everolimus) tablets has been approved by the US Food
and Drug Administration (FDA) for patients with advanced renal cell carcinoma (RCC) after
failure of treatment with Sutent(R) (sunitinib) or Nexavar(R) (sorafenib).
Prior to Afinitor, no other therapy has been studied in a Phase III trial in this patient population
where there is an important unmet medical need(1). Sutent and Nexavar are commonly used
as initial treatments for advanced RCC(2).
The approval is based on data that showed Afinitor, when compared with placebo, more than
doubled the time without tumor growth or death in patients with advanced kidney cancer (4.9
vs. 1.9 months) and reduced the risk of disease progression or death by 67% (hazard
ratio=0.33 with 95% confidence interval 0.25 to 0.43; P<0.0001)(3). Furthermore, additional
data show that after 10 months of treatment with Afinitor, approximately 25% of patients still
had no tumor growth(1) .
"This approval provides a new and useful tool for treating advanced renal cell cancer,
representing an important step forward in managing this disease," said Robert J. Motzer, MD,
attending physician, Memorial Sloan-Kettering Cancer Center, New York and principal
investigator of the RECORD-1 trial, the basis for FDA approval of Afinitor. "New treatment
options are vital to help us continue to offer patients with advanced kidney cancer new ways to
battle their difficult-to-treat disease. Based on clinical trial data, this option should be
considered when sunitinib or sorafenib fail."
In 2008, the FDA granted priority review status to Afinitor, previously known as RAD001, based
on its potential to fill an unmet medical need for patients with advanced kidney cancer. Novartis
has filed regulatory submissions in the European Union, Switzerland and Japan, as well as
with other regulatory agencies globally(1).
Afinitor inhibits mTOR, a protein in the cancer cell that controls tumor cell division and blood
vessel growth. Preclinical and clinical data have established the important role of mTOR in the
development and progression of several types of tumors(1).
"With this approval, we can now offer patients a targeted therapy proven to fulfill an important
unmet need in the treatment of advanced kidney cancer," said David Epstein, President and
CEO, Novartis Oncology, Novartis Molecular Diagnostics. "We continue to study Afinitor in
kidney cancer, and through a broad clinical program to explore its potential in many other
tumor types."
About renal cell carcinoma
Renal cell carcinoma is often referred to as kidney cancer. Kidney cancer accounts for
247
approximately 2% of all new cancers(4). RCC is the most common type of kidney cancer, with
occurrence rates rising steadily around the world due in part to smoking and obesity(5,6). It is
estimated that about 54,000 new cases of RCC developed in the US in 2008 and more than
13,000 people died from the disease(7).
In RCC, cancer cells develop in the lining of the kidney's tubes and grow into a tumor(8). If left
untreated, the tumor can spread to neighboring lymph nodes and eventually other organs(9).
RECORD-1 trial
The FDA regulatory filing for Afinitor was based on data from RECORD-1 (REnal Cell cancer
treatment with Oral RAD001 given Daily), the largest Phase III clinical trial to study the effects
of an oral mTOR inhibitor in advanced RCC patients whose cancer progressed despite prior
treatment with sunitinib, sorafenib or both sequentially. In February 2008, based on a
recommendation from an independent data monitoring committee, Novartis stopped the trial
after interim results showed that patients receiving Afinitor experienced a significant delay in
cancer progressing or death compared with patients receiving placebo(1).
This international, multi-center, randomized, double-blind trial involved 416 patients with
advanced RCC whose cancer progressed despite prior treatment with sunitinib, sorafenib or
both sequentially. In addition, prior therapy with bevacizumab, interferon alfa and interleukin-2
was allowed. Patients were randomized to receive Afinitor (10 mg) daily or placebo, in
conjunction with best supportive care. The primary endpoint of the study was progression-free
survival, which was assessed via a blinded independent, central radiological review(10).
About Afinitor
Afinitor is the first oral, daily therapy (5 mg and 10 mg tablets) to treat advanced kidney cancer
after failure of treatment with sunitinib or sorafenib. In cancer cells, Afinitor continuously
targets mTOR, a protein that acts as a central regulator of tumor cell division, blood vessel
growth and cell metabolism. Afinitor is also being studied in multiple cancer types, including
neuroendocrine, breast, gastric and hepatocellular carcinoma (HCC), as well as tuberous
sclerosis complex (TSC) and non-Hodgkin's lymphoma(11).
The active ingredient in Afinitor is everolimus, which is available in different dosage strengths
under the trade name Certican(R) for the prevention of organ rejection in heart and kidney
transplant recipients. Certican was first approved in the EU in 2003. Certican is not approved
for use in the US(1).
Important safety information
Afinitor is contraindicated in patients with hypersensitivity to everolimus, to other rapamycin
derivatives or to any of the excipients. Potentially serious adverse reactions include
non-infectious pneumonitis and infections for which patients should be monitored carefully and
248
treated as needed. In addition, non-infectious pneumonitis may require temporary dose
reduction and/or interruption or discontinuation. Patients with systemic invasive fungal
infections should not receive Afinitor. Oral ulceration is a common side effect with Afinitor.
Renal function, blood glucose, lipids and hematological parameters should be evaluated prior
to the start of therapy with Afinitor and periodically thereafter. Strong or moderate CYP3A4 or
P-glycoprotein inhibitors should be avoided. An increase in the dose of Afinitor is
recommended when co-administered with a strong CYP3A4 inducer. Live vaccinations and
close contact with those who have received live vaccines should be avoided. Afinitor should
not be used in patients with severe hepatic impairment. Afinitor may cause fetal harm in
pregnant women.
The most common adverse reactions (incidence greater than or equal to 30%) were stomatitis,
infections, asthenia, fatigue, cough and diarrhea. The most common grade 3/4 adverse
reactions (incidence greater than or equal to 3%) were infections, dyspnea, fatigue, stomatitis,
dehydration, pneumonitis, abdominal pain and asthenia. The most common laboratory
abnormalities (incidence greater than or equal to 50%) were anemia, hypercholesterolemia,
hypertriglyceridemia, hyperglycemia, lymphopenia and increased creatinine. The most
common grade 3/4 laboratory abnormalities (incidence greater than or equal to 3%) were
lymphopenia, hyperglycemia, anemia, hypophosphatemia and hypercholesterolemia. Deaths
due to acute respiratory failure (0.7%), infection (0.7%) and acute renal failure (0.4%) were
observed for patients receiving Afinitor.
Disclaimer
The foregoing release contains forward-looking statements that can be identified by
terminology such as "risk," "options," "potential," "continue to study," "explore," "estimated,"
"can" or similar expressions, or by express or implied discussions regarding potential new
indications or labeling for Afinitor, potential approvals of Afinitor in additional markets, or
regarding potential future revenues from Afinitor. You should not place undue reliance on these
statements. Such forward-looking statements reflect the current views of the Company
regarding future events, and involve known and unknown risks, uncertainties and other factors
that may cause actual results with Afinitor to be materially different from any future results,
performance or achievements expressed or implied by such statements. There can be no
guarantee that Afinitor will be approved for sale in any additional markets. Neither can there be
any guarantee that Afinitor will be approved for any additional indications or labeling in any
market. Nor can there be any guarantee that Afinitor will achieve any particular levels of
revenue in the future. In particular, management's expectations regarding Afinitor could be
affected by, among other things, unexpected regulatory actions or delays or government
regulation generally; unexpected clinical trial results, including unexpected new clinical data
and unexpected additional analysis of existing clinical data; the company's ability to obtain or
maintain patent or other proprietary intellectual property protection; competition in general;
government, industry and general public pricing pressures; the impact that the foregoing
factors could have on the values attributed to the Group's assets and liabilities as recorded in
the Group's consolidated balance sheet, and other risks and factors referred to in Novartis
249
AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one
or more of these risks or uncertainties materialize, or should underlying assumptions prove
incorrect, actual results may vary materially from those anticipated, believed, estimated or
expected. Novartis is providing the information in this press release as of this date and does
not undertake any obligation to update any forward-looking statements contained in this press
release as a result of new information, future events or otherwise.
About Novartis
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of
Novartis AG which provides healthcare solutions that address the evolving needs of patients
and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet
these needs: innovative medicines, preventive vaccines, diagnostic tools, cost-saving generic
pharmaceuticals and consumer health products. Novartis is the only company with leading
positions in these areas. In 2008, the Group's continuing operations achieved net sales of
USD 41.5 billion and net income of USD 8.2 billion. Approximately USD 7.2 billion was
invested in R&D activities throughout the Group. Headquartered in Basel, Switzerland,
Novartis Group companies employ approximately 96,700 full-time-equivalent associates and
operate in more than 140 countries around the world. For more information, please visit
http://www.us.novartis.com.
References
1. Novartis data on file.
2. National Comprehensive Cancer Network. "NCCN Clinical Practice Guidelines in Oncology:
Kidney Cancer."
3. Prescribing Information for Afinitor.
4. McLaughlin JK, et al. Epidemiologic aspects of renal cell carcinoma. Semin Oncol.
2006;33(5):527-533.
5. American Cancer Society. "What Is Kidney Cancer (Adult) - Renal Cell Carcinoma?"
6. Eisen, et. al. "Sorafenib for Older Patients with Renal Cell Carcinoma." J. Natl Cancer Inst.
2008;100(20):1454-1463.
7. American Cancer Society. "What Are the Key Statistics for Kidney Cancer?" Available at
http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_ki
dney_cancer_22.asp?sitearea=. Accessed March 2009.
8. National Cancer Institute. "General Information About Renal Cell Cancer." Available at
http://www.cancer.gov/cancertopics/pdq/treatment/renalcell/patient. Accessed March 2009.
250
9. American Cancer Society. "How Is Kidney Cancer (Renal Cell Carcinoma) Staged?"
Available
at
http://www.cancer.org/docroot/CRI/content/
CRI_2_4_3X_How_is_kidney_cancer_staged_22.asp?rnav=cri. Accessed March 2009.
10. Escudier, B. et al. Phase-3 randomized trial of everolimus (RAD001) vs. placebo in
metastatic renal cell carcinoma. Presented at the European Society for Medical Oncology
(ESMO) 33rd Congress on September 16, 2008.
11. A service of the U.S. National Institutes of Health. Available at http://clinicaltrials.gov.
Accessed March 2009.
Sutent(R) is a registered trademark of Pfizer Inc.
Nexavar(R) is a registered trademark of Bayer HealthCare Pharmaceuticals, Inc. and Onyx
Pharmaceuticals.
Data from RECORD-1 study findings presented at the 33rd European Society for Medical
Oncology Congress.
Novartis Pharmaceuticals Corporation
http://www.us.novartis.com
View drug information on Nexavar; Sutent.
3 月 31 日
Improving Cancer Therapy Achieved Through Taste, Odor Intervention
Cancer and its therapies, including chemotherapy and radiotherapy, may directly alter and
damage taste and odor perception, possibly leading to patient malnutrition, and in severe
cases, significant morbidity, according to a Virginia Tech Wake Forest University
Comprehensive Cancer Center compilation of various existing studies. Their review appears in
the March/April 2009 Journal of Supportive Oncology.
One of the purposes of the study, said Andrea Dietrich, professor of civil and environmental
engineering (CEE) at Virginia Tech, is to provide researchers and physicians with a better
understanding of the types and causes of taste and odor dysfunctions so that they can develop
treatments for these conditions and improve the quality of life of their patients. According to
Susan Duncan, professor of food science and technology at Virginia Tech, a bad taste in the
mouth can lead to poor nutrition because patients avoid eating.
Approximately two thirds of cancer patients who receive chemotherapy report altered sensory
perception, such as decreased or lost taste acuity or metallic taste. Altered sensory perception
causes psychological anxiety and malnutrition, and thus negatively impacts the chances of
survival for cancer patients, as reported in an earlier study conducted by Duke University.
Dietrich, an expert on water quality and treatment, as well as the taste and odor assessment of
251
water, has expanded upon her knowledge of this field to include such assessments in cancer
patients. She worked with Jae Hee Hong, Susan E. Duncan, and Brian T. Stanek of Virginia
Tech's Food Science and Technology Department, Pinar Omur-Ozbek, also of CEE, Yong Woo
Lee of Virginia Tech's School of Biomedical Engineering and Glenn Lesser, a physician of
hematology and oncology at Wake Forest.
Their joint paper, "Taste and Odor Abnormalities in Cancer Patients," reports the "alteration of
taste and smell in (cancer) patients has been understudied compared with other aspects of
cancer research."
They based their work on numerous previous studies that reported on changes in taste acuity,
taste quality, odor perception, food aversion, and xerostomia (dry mouth) causing taste
alteration. Findings from these studies showed changes in taste acuity are dependent on the
site of the tumor with head and neck patients reporting more complaints than do patients with
other types of cancer such as breast or lung. The most prevalent taste alteration reported is
the perception of a metallic or bitter taste, with red meat often cited as a cause. Another earlier
study showed aversion to food is now occurring in as much as 55 percent of the patients
receiving chemotherapy or radiotherapy.
From their review of the literature, the research team put together a listing of management
strategies to improve taste and odor abnormalities for cancer patients. These include: avoiding
the use of metallic silverware and reducing the consumption of foods that have a metallic or
bitter taste such as red meat, coffee or tea. On the positive side, patients should increase their
consumption of high-protein foods, add seasonings and spices to enhance flavors in some
cases, practice good oral hygiene, and use agents such as sugar free gums and sour tasting
drops to stimulate salivary secretion.
Dietrich explained their study of the literature, and synopsis of it, is meant to increase the
recognition by oncologists and physicians of the disturbances cancer patients experience in
their ability to taste and smell. "Oncologists who understand the types and causes of taste and
olfactory abnormalities may be better prepared to discuss and empathize with these negative
side effects," she and her colleagues concluded. And physicians could improve their
relationships with their patients, sharing "possible mediation strategies," and directly affecting
the recovery of patients.
Virginia Tech (Virginia Polytechnic Institute and State University)
Rm. 1, Media Bldg. (0109)
Blacksburg
VA 24061
United States
http://www.vt.edu
3 月 31 日
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Researchers Discover And Manipulate Molecular Interplay That Moves
Cancer Cells
Based on research that reveals new insight into mechanisms that allow invasive tumor cells to
move, researchers at the Mayo Clinic campus in Florida have a new understanding about how
to stop cancer from spreading. A cancer that spreads elsewhere in the body, known as
metastasis, is the process that most often leads to death from the disease.
In the March 29 online issue of Nature Cell Biology, researchers say that a molecule known as
protein kinase D1 (PKD1) is key to the ability of a tumor cell to "remodel" its structure, enabling
it to migrate and invade. The researchers found that if PKD1 is active, tumor cells cannot move,
a finding they say explains why PKD1 is silenced in some invasive cancers.
During metastasis, invasive cancer cells respond to biological signals to move away from a
primary tumor. Multiple research groups at Mayo Clinic in Florida are especially interested in
this process. One team, led by cancer biologist Peter Storz, Ph.D., has been investigating a
process known as actin remodeling at the leading edge - the most forward point - of these
migrating tumor cells.
"The events that reorganize the actin cytoskeleton at the leading edge are complex a multitude
of molecules act in concert," Dr. Storz says. "But it appears that PKD1 must be turned off if
cancer cells are to migrate."
Actin filaments help make up the cytoskeleton of cells. For cancer cells to move, the
actin-based cell structure has to be continually reorganized, Dr. Storz says, and to do this, new
actin filaments need to be generated to shift the cell forward.
Dr. Storz' group discovered that PKD1 was critical to this process. The researchers found that
PKD1 inhibits another protein known as slingshot, which regulates the severing of existing
actin structures so that new actin filaments can be synthesized, an event that is essential for
cell movement.
The researchers used methods to deplete tumor cells of PKD1 and found that their motility
increased. They then expressed activated PKD1 in tumor cells and found that movement was
blocked. PKD1 is therefore a negative regulator of directed cell migration, and if PKD1 is not
expressed in tumor cells, slingshot will become active and will contribute to the reorganization
of actin, and a tumor cell will move, according to researchers.
"This makes sense, because other investigators have found that PKD1 is down-regulated, or
turned off, in invasive forms of gastric, prostate, and breast cancer," says Dr. Storz.
So far, investigators have identified a number of players along the pathways that regulate
cancer cell movement, from the molecule (RhoaA) that activates PKD1, to the well-known
protein (cofilin) that disassembles actin filaments and which is regulated by slingshot. When
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PKD1 is activated, cofilin does not function and so the cell cannot move.
"Now that we have identified PKD1 as key regulator in processes regulating actin-based
directed tumor cell movement, we can begin to think about designing treatments to stop
invasive cancer cells from metastasizing," says Dr. Storz. "The basic mechanisms we have
uncovered are key to developing those strategies."
Co-authors include Tim Eiseler, Ph.D., Heike Döppler, and Irene Yan from the Mayo Clinic
Department of Cancer Biology; and Kanae Kitatani, Ph.D., and Kensaku Mizuno, Ph.D., from
the Graduate School of Life Sciences at Tohoku University in Japan.
The study was funded by Mayo Foundation and the Mayo Comprehensive Cancer Center, the
National Cancer Institute, a 'Friends for an Earlier Breast Cancer Test' Grant, and by a
grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science, and
Technology of Japan.
Mayo Clinic
200 First St. SW
Rochester
MN 55902
United States
http://www.mayoclinic.com
3 月 31 日
Novartis Kidney Cancer Drug Gets US Approval
The US Food and Drug Administration (FDA) announced on Monday that it had approved
Afinitor oral tables (everolimus) for the treatment of advanced kidney cancer in patients where
the disease continued to progress after treatment with other drugs.
Afinitor is manufactured by Novartis International AG of Basel, Switzerland.
Dr Robert Justice, director of the Division of Drug Oncology Products in the FDA's Center for
Drug Evaluation and Research (CDER) said:
"Afinitor provides an option for patients with advanced renal cell cancer after failure of
treatment with the cancer therapies sunitinib [Sutent, from Pfizer] or sorafenib [Nexavar, from
Bayer]."
"Targeted cancer therapies like Afinitor have increased the number of months patients can live
without the tumor progressing," he added.
The most common form of kidney cancer is renal cell carcinoma, which starts in the lining of
the tiny tubules inside the kidney that clean the blood by filtering out the waste products of
metabolism and other body processes. It accounts for about 2 per cent of all new cancers and
rates of new cases are going up worldwide, partly because of smoking and obesity, according
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to sources cited in a Novartis press statement.
Renal cell carcinoma resists standards treatments like radiotherapy and chemo, and treatment
usually starts with surgical removal of the affected kidney. If the cancer hasn't spread outside
of the affected kidney, five year survival can be as much as 60 to 70 per cent, but it is much
lower if the cancer has spread.
Afinitor is a kinase inhibitor: it stops tumors growing by blocking a specific protein called mTOR,
the mammalian target of rapamycin. This action stops the cell to cell communications that help
cancer cells to grow, divide and metabolize. In contrast, Sutent and Nexavar are multiple
kinase inhibitors and work on several targets at the same time.
The FDA approval relied on the results of the RECORD-1 clinical trial that tested the safety
and effectiveness of Afinitor given as a daily oral dose against placebo. The trial was stopped
early because interim results showed that patients taking the drug experienced delayed tumor
growth and spread compared to those who did not. Also, disease progression was delayed for
about five months in 50 per cent of the patients who took the drug compared to only 2 months
for those who did not.
According to the FDA announcement, the most frequent adverse reactions (1 in 5 patients had
them) included: "inflammation in the mouth, loss of strength, diarrhea, poor appetite, fluid
buildup in the extremities, shortness of breath, coughing, nausea, vomiting, rash, and fever".
Lab tests of blood samples also showed that at least half the patients were anemic, had low
white blood counts, high cholesterol, high blood sugar and high triglycerides (blood fats), said
the agency.
Dr Robert J Motzer, attending physician, Memorial Sloan-Kettering Cancer Center, New York
and principal investigator of the trial told the press that:
"This approval provides a new and useful tool for treating advanced renal cell cancer,
representing an important step forward in managing this disease."
"New treatment options are vital to help us continue to offer patients with advanced kidney
cancer new ways to battle their difficult-to-treat disease. Based on clinical trial data, this option
should be considered when sunitinib or sorafenib fail."
Novartis said in a press release that it has also filed for approval of Afinitor in the European
Union, Switzerland and Japan, as well as with other regulatory agencies globally and that
Phase III trials are underway to explore the potential of the drug in treating several other
cancers.
David Epstein, President and CEO, Novartis Oncology, Novartis Molecular Diagnostics said:
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"We continue to study Afinitor in kidney cancer, and through a broad clinical program to
explore its potential in many other tumor types."
3 月 31 日
Pathwork Tissue Of Origin Test Validation Study Published In Journal Of
Clinical Oncology
Pathwork Diagnostics, Inc., a molecular diagnostics company focused on oncology,
announced that the Journal of Clinical Oncology (JCO) has published the results of the
Pathwork(R) Tissue of Origin Test validation study in a paper entitled, "Multicenter Validation of
a 1,550-Gene Expression Profile for Identification of Tumor Tissue of Origin." The results of the
547-specimen study showed that the test has significant potential to reduce diagnostic
uncertainty for poorly differentiated, undifferentiated or metastatic tumors. To date, no other
tests in this category have undergone as large a clinical validation study or produced such
strong results.
"This study, which is the first of many clinical studies being performed, clearly demonstrates
the exceptional performance and robust science underlying our test," said Deborah J. Neff,
President and Chief Executive Officer of Pathwork Diagnostics. "We believe the Tissue of
Origin Test can benefit physicians by allowing them to diagnose tumors with uncertain origins
with greater confidence because the test provides objective data and the ability to both rule in
and rule out tumor types."
To determine the tumor's origin, the Pathwork Tissue of Origin Test uses microarray
technology to measure the gene expression pattern, comprising more than 1,500 genes, in a
tumor with an uncertain origin and compare it to expression patterns of a panel of 15 known
tumor types, representing 90 percent of all solid tumors and 58 morphologies overall. In the
multicenter, blinded clinical validation study, which was used as the basis for the test's FDA
clearance in July 2008, the test examined 547 frozen tumor specimens from patients
diagnosed with one of the tumor types in the panel, all of which were either metastatic, poorly
differentiated or undifferentiated. The test demonstrated 88% positive percent agreement (akin
to sensitivity) and greater than 99% negative percent agreement (akin to specificity) with
available diagnoses. Although the JCO paper only reported results for frozen tissue samples, a
separate
validation
study
performed
by
Pathwork
with
FFPE
(formalin-fixed,
paraffin-embedded) specimens showed similar performance. Both the frozen and FFPE
versions of the test are commercially available as a service through Pathwork Diagnostics
Laboratory.
The paper published in the American Society of Clinical Oncology's journal was authored by
Federico Monzon, M.D., Director of Molecular Diagnostics at The Methodist Hospital in
Houston, Texas. Dr. Monzon's results showed that the test should become a valuable
complement to currently available diagnostic methods for tumors with uncertain origins. The
abstract can be read online at http://jco.ascopubs.org.
About Pathwork Diagnostics
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Pathwork Diagnostics, Inc., based in Redwood City, Calif., develops and commercializes
high-value molecular diagnostics for oncology. The company's first test to market - the
Pathwork(R) Tissue of Origin Test - utilizes proprietary analytics and a companion Pathchip(R)
microarray, which runs on the proven Affymetrix GeneChip(R) System.
Copyright (C) 2009 Pathwork Diagnostics, Inc. All rights reserved. Pathwork, Pathchip,
Pathwork Diagnostics, and the Pathwork Diagnostics and the Pathwork Tissue of Origin logos
are trademarks or registered trademarks of Pathwork Diagnostics, Inc. Other names may be
the trademarks of their respective owners.
Pathwork Diagnostics, Inc.
http://www.pathworkdx.com
3 月 31 日
University Hospitals In Germany And Switzerland Treat Complex Cancer
Cases Using RapidArc(TM) Radiotherapy Technology
Leading University Hospitals in Germany and Switzerland have commenced treatments for
complex cancers, including head & neck tumors, using RapidArc(TM) radiotherapy technology
from Varian Medical Systems (NYSE: VAR). Gottingen University Hospital in Germany and
Zurich University Hospital in Switzerland are amongst the earliest implementers of this new,
fast form of image-guided intensity modulated radiotherapy (IMRT), which potentially enables
doctors to improve outcomes while extending modern care to more patients.
Varian's RapidArc delivers a precise and efficient treatment in single or multiple arcs of the
treatment machine around the patient and makes it possible to deliver image-guided IMRT two
to eight times faster than is possible with conventional IMRT.
Gottingen University Hospital
Doctors at Gottingen University Hospital are focusing early RapidArc treatments on what they
describe as 'difficult' cases. "Today we are treating a nasopharyngeal cancer patient with a
boost of RapidArc because we could not create an acceptable IMRT plan, so there are clearly
some patients for whom RapidArc offers a more appropriate treatment," says physician Dr.
Hilke Vorwerk.
Dr. Vorwerk said they will begin RapidArc treatments for patients with head and neck tumors
and prostate cancer. "Our experience so far is that in most cases RapidArc is as good as
conventional IMRT and in some cases superior, as well as being considerably faster, which is
important for patient comfort but also for treatment precision as there is less patient motion,"
she said. Gottingen University Hospital has the only radiotherapy department south of
Niedersachen and treats up to 2,000 new cancer patients each year.
"Up to now we have not had a major problem with waiting lists but cancer referrals have
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increased by 150 percent in the last two years, so faster treatments will give us extra capacity
to meet this growing demand," added Dr. Vorwerk. "In addition, more patients will be able to
receive the most modern treatments available."
Zurich University Hospital
At Zurich University Hospital, a 55-year-old patient with a recurrence of a previously-operated
tonsil cancer received RapidArc radiotherapy treatment from Dr. Gabriela Studer and her team.
"Our first RapidArc treatment involved a difficult plan because we were treating lymph node
metastases and we were very impressed by the speed of the new treatment," says Dr. Studer.
"Here in Zurich we have a long history of delivering IMRT treatments and we focus strongly on
complicated head and neck tumors. For such treatments, RapidArc is an extremely valuable
new capability to meet our goals. Our first patient particularly appreciated the faster treatment
because she suffers from claustrophobia and finds it daunting to lie on the treatment table for
very long, so having a fast and open system is a major advantage over slower treatments in a
tunnel-like system. Also, the system's cone-beam CT capabilities allow us to implement an
adaptive radiotherapy approach where we see big changes in the size and shape of the tumor
during treatment."
Zurich University Hospital and Gottingen University Hospital are among more than 70
institutions in the world with the new RapidArc treatment capability for image-guided IMRT.
Conventional IMRT treatments are slower and more difficult for radiotherapy radiographers
because they target tumors using a complex sequence of fixed beams from multiple angles
About Varian Medical Systems
Varian Medical Systems, Inc., of Palo Alto, California, is the world's leading manufacturer of
medical devices and software for treating cancer and other medical conditions with
radiotherapy, radiosurgery, proton therapy, and brachytherapy. The company supplies
informatics software for managing comprehensive cancer clinics, radiotherapy centers and
medical oncology practices. Varian is a premier supplier of tubes and digital detectors for X-ray
imaging in medical, scientific, and industrial applications and also supplies X-ray imaging
products for cargo screening and industrial inspection. Varian Medical Systems employs
approximately 5,100 people who are located at manufacturing sites in North America and
Europe and in its 60 sales and support offices around the world. For more information, visit
http://www.varian.com.
Varian Medical Systems, Inc.
http://www.varian.com
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