BIO 501
The Biology of Cancer
Introduction to 501
Folder Title: Intro501.ppt
On course web-site:
Intro501(NoTP).ppt
Updated: January 25, 2016
This is a Turning Point Slide to Open
the System to Accept Your
Transmitted Questions. No need to
answer.
Rank
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NewsWeek
Oct. 26, 2009
Try Newsweek.com
We will try to make
color copies for
everyone if we can
make that work.
Why Does Cancer Matter?
President Obama’s State of the Union:
“Moon-shot” Program to Cure Cancer
Headed by Vice President Biden
Cancer in the United States:
1.7 million new cases per year.
600,000 Deaths
Colo-rectal
Prostate
Lung
Pancreas
Peak
1990!
Surgeon General
Luther Terry’s Report to Congress
and the Nation: 1964
Cancer Death Rates* Among Women, US,1930-2009
Peak
2005
Total Number of Cancer Deaths Averted from
1991 to 2009 in Men and 1992 to 2009 in
Women
Phenomenology of Cancer:
Features of Cancers in Human Populations
Extent and Clinical Patterns of Cancers
Epidemiology of Cancers
Classification and Nomenclature
What do these features tell us about the basic biology
of cancer?
What do these features tell us about Diagnosis,
Management (therapy),
and Prevention of Cancers?
What Models of Cancers Do We Actually Use in
Cancer Biology and Cancer Medicine?
Cells in Cell Culture (“In Vitro”)
Neoplastic and Normal Cell Lines in Culture
Transformed Normal Cells
Freshly-derived Cancer Cells
Genetically Engineered Cells
Engineered Tissues (3-Dimensional Cell Cultures)
Animal Models in Cancer Research and Medicine (“In Vivo”)
Inbred Animal Models
Veterinary Animals
Animal-Human Engineered Hybrid Models
Clinical Cancer in Patients (“In Vivo”)
Clinical Trials (Phase I, Phase II, and Phase III)
What are Cancer Cells Like?
As Isolated Cells?
In Tumor-bearing Animals?
In Patients? (See Slide 31 Videos Later)
Characteristics of Cancer Cells in Culture
How does a Cancer Cell “Talk” to Itself and Its Neoplastic Neighbors?
Why are cancer cells in cell culture Immortal?
Tumor Cell Populations and Tumor Tissues in vivo
How do Cancer Cells “Talk” to each other?
How do Cancer Cells “Talk” to normal cells?
What do cancer cells “hear” from the host?
Why don’t cancer cells know how old they are and when to die?
Growth Patterns of Experimental and Clinical Cancers
How Do Cancer Cells Change and Progress in Malignant Potential?
What are the Patterns of Invasion & Spread to Distant Sites?
What Are the Genetics Underlying Cancers?
What does modern genomics tell us about cancer biology,
origins of cancer, cancer diagnosis and treatment?
What are the crucial features of cancer cell genomes?
What are the hereditary patterns in tumor-bearing hosts?
What are the clonal origins of cancers?
What do Proteomics (the spectrum of expressed proteins)
and Epigenetics* tell us about Cancer origins and
progression?
*(modification of genes and gene-products)
Differentiation and Cancer:
Cancer as an expression of abberrant
differentiation
How are genes expressed and controlled in cancer?
Can the malignant state be reversed to normal?
Why are oncofetal genes often re-expressed in
cancers?
Biological Mechanisms Underlying
Cancer Phenomenology
Cell Cycle, Proliferation, Signalling, and Immunogenicity
Cellular Senescence, Immortalization, and Cancer
Cell Death (Genetically-programmed cell death; Apoptosis)
Telomeres and Cell Ageing
Autophagy (Inter-cellular “cannibalism”) and Cancer
Intra-cellular signaling
Growth Factors and Receptors
Inter-cellular Communication
Cell Movement
Gene Expression and Differentiation Control
Normal Immune Responses and Immune Escape
Protein Structure, Function, and Modification
Onco-fetal gene products
Basic Biology in the Diagnosis and Therapy of Cancers
Modalities in Cancer Management:
Diagnosis, Surgery, Chemotherapy, Immunotherapy, Radiation Therapy
(X-ray, Radio-isotopes, Ultra-sound?), Cell Therapy, Gene Therapy
Host Response Modifiers
Genetics and Cancer Management
Immunotherapy & Immunodiagnosis of Cancers
Cancer Chemotherapy
New Approaches to Cancer Management
Specific Targeted Therapy
“Phenotherapy” of Cancer?
To Enter your name on your NXT Transmitter
(Revised January 19, 2016)
For NXT Transmitter (Off-white)
Press grey button with white oval in the middle
Get screen with a wrench on it
Press upper right button (square with two bubbles)
“Find Channel” (Channel 41)
Press Right Arrow 4 times to get to “Your ID”
Grey Button
(Left arrow under abc will clear characters)
Enter your name (first five letters OK) using the letters shown on each key.
If you want a “c”, hit the abc key three times in quick succession.
When your name is entered hit the grey button.
You will get a smiley face.
_______________________________________________________________
To Send in a “Response to Leader” Question at any time during class:
See Instructions on Next Slide
(Your ID but not your name will show)
Type in your message. I will get an icon on my screen to see what was asked.
How to use your NXT Transmitter
(Revised January 11, 2015 by Yifan)
Find channel and edit names
• Press grey button with white oval in
the middle
• Main screen should be seen as shown
in picture on the right side
• Press upper right button to go to
Toolbox
• Go to “Find Channels” and make
sure you are on the right channel
(Channel 45)
• Press Right Arrow 4 times to get to
“Your ID”
• Enter your name (first five letters
OK) using the letters shown on each
key.
 Left arrow under abc will clear characters
 If you want a “c”, hit the abc key three times
in quick succession.
 When your name is entered hit the grey
button.
 You will get a smiley face.
To Answer Quiz Questions See Next
Slide
Send response to Professor
• To Send in a “Response to Leader” at
any time during class, go to Toolbox,
select “Send Message”, type in your
questions in there, professor will get
an icon on his screen to see what was
asked. (Your name will NOT be
shown on screen)
• BE CAREFUL! Do not answer quiz
questions under this “Send Message”
function! Your answer input here will
NOT be received. You have to go to
main screen (See picture above) to
answer question.
To Respond to Turning Point Questions in Class:
Using the NXT Transmitter
(Revised January 10, 2016
1. Put your last name onto your transmitter under “Your ID” for NXT
2. If you borrow a transmitter from us, fill out an index card, take instruction form, leave the
device ID unchanged on the borrowed transmitter. We will know who y ou are form the index
card that you filled out on the date when you borrowed our transmitter. Do not change the
“BIO” designation.
3. We are using Channel 45 in this room. NXT should find Channel 45 when you hit “Find
Channel”. You get a smiley face.
4. Respond to the question on the screen as directed on the question itself.
5. With NXT you have to hit the square response button in the upper left below the screen in
order to get to the blank screen that is presentation mode.
6. Screen will show whether your response has been received. Your device will also show a check
when your name has been received.
7. Non-response grid will be displayed on the presentation screen in the front of the room.
8. You must respond quickly because we cannot allow for open-ended time for response because
it opens the opportunity for cheating.
9. We count persons in class and match that number with the TP responses + Backup Forms.
10. If the numbers don’t agree, we hand out paper forms one-at-a-time. The person or persons
who have someone else respond for them will be dismissed from the class
Use of Back-up forms
1. If you have a condition or language problems that prevents your
entering a response quickly, you can use back-up forms provided by us but
you have to sit in the first row in the classroom to allow for access to the
back-up forms and for our collecting them.
2. If you have problem with your NXT transmitter we can provide a paper
back-up form if absolutely unavoidable. However, you must hand in the
back-up form with your response at the same time that the question is
being responded to by the rest of the class.
3. You must identify yourself with your SUID photo card when you hand
in a back-up form so we know that the form has been filled out by the
person who hands it in.
The Next Three Slides are Turning Point Quiz Question Slides
You may not use any notes or electronic devices other than your
NXT transmitter. No computers. No phones. No “smart” watches.
No talking or consulting. No looking side-to-side or to the row in
front of your seat.
If you see anyone doing something suspicious, send the seat row
and number to me. This does not imply an accusation of
cheating. It simply notifies me to keep my eyes open.
Make sure that your desk is clear.
These are graded quizzes that make up 40% of the overall course
grade. Cheating hurts everyone and damages the value of the
course.
They are designed for both you and me to determine whether you
are paying attention and following what is going on.
With your name entered under Device ID:
To get a blank screen that accepts your response:
repeatedly push the black square button in the upper left
of the NXT device. When you get the blank screen,
respond to the question:
I am here!
1. Yes
2. No
Response
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This is a fill-in-the-blank question:
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Course Evaluation, Grading,
and Maintenance of Standards
Three In-Class Exams, 100 Pts Each
Tuesday February 23rd, After Classes 1 to 10
Tuesday, March 29th , After Classes 11 to 19
During Assigned Finals Time after Classes 20 to 28
Class Participation Components at Every Class:
Based on Responses Using Turning Point NXT-Transmitters
200 Points Maximum Possible (40% of Course Grade)
Course Web-Site
Integrated Web-site at http://tpfondy.syr.edu/bio501
is a crucial element of this course.
See Class Schedule and Graphics on Course Main Web-Page
Presentations without the Turning Point Questions are made
available to make note-taking easier.
The course itself is presented by me orally with graphics on the
screen in front of the room.
The Online presentations are not the course.
To Send in a “Response to Leader” at any time during class:
See Slides 16 & 17 and Handout from Class of January 19th
(Your ID but not your name will show)
Type in your message. I will get an icon on my screen to
see what was asked.
Textbook:
Biology of Cancer
Robert A. Weinberg
Garland Science, 2014
Second Edition
CD with Movies, Mini-lectures,
Pathways in Cancer Poster,
Powerpoint and JPEG Versions of Textbook Graphics
To Here, Presentation 1, Jan. 19, 2016
Scope of Disciplines in Basic Sciences
Involved in Biology of Cancer
Cell Biology
Genetics
Molecular Biology
Biochemistry
Immunology
Microbiology*/Virology
Developmental Biology
Physiology
Environmental Biology
Histology
Pathobiology
Pharmacology
Epidemiology
Neurobiology
Organic Chemistry
Physics
Statistics
Computer Information Sciences
* A Note on Cancer Biology, the Iceman, and Science, January 6, 2016
Some Conceptual Goals in Biology of Cancer Course
Overview of Cancer Biology: What Does One Study?
How Do Cancer Biologists Think?
How Are Questioned Formulated?
How are Experiments and Trials Designed?
What (Who) Do Cancer Biologists Work On?
What are the Real Questions and the Limitations?
What are the Currently Best Prospects for:
Improved Understanding of the Biology of Cancer?
Prevention?
Improved Diagnosis, Management, and Cures?
What Do Terms in Oncology Mean?
e.g. What is the difference between a myeloid neoplasm and a
myogenic neoplasm?
What is Cancer Like:
As a Biological Manifestation?
As a Clinical Problem?
As a Problem for People?
Why Study the Biology of Cancer?
Cancer Incidence, Morbidity, and Mortality
• 1,638,910 New Cases 2012- US; 1,660,290 (2013); 1,665,540 (2014)
Why the increase? Population Increase; Earlier and better diagnosis;
Ageing of population; Actual increased incidence
• ~12,000,000 New Cases per Year - World-Wide
• 580,350 Deaths 2013- US ; 585,720 (2014) This is a 35% death rate!
(Higher death rate based on using 2009 incidence rate and 5 yr survival
• 1,590 Deaths per Day – 2013 U.S. ; 1,605 (2014)
• ~6,000,000 Deaths per Year - World-Wide
• 1 in 200 out of 310 Million (US) presented with Cancer in 2014
• Lifetime Risk of presenting with Cancer ~ 40%
(assuming 80-year lifespan and no change in incidence
• 1 in 600 will die of Cancer in 2016 (0.18% of US Population)
• Lifetime Risk of Death ~13%
• Protracted, Degenerative, Dehumanizing Diseases
• 1.8% of Cancer Deaths are Children ages 1 to 14
(10,800 deaths per year)
What are Cancers like in Patients?
What do clinicians see?
What are they dealing with?
Why Cancer Matters: Take 2
Taylor Black’s Presentation at American Cancer Society Meeting
(7 minutes)
Presented in Class, Thursday, January 21st, 2016
60 Minutes Story of Taylor Black with Ben Bradley
(Part from 15 to 27 minutes)
To Be Presented in Class, Tuesday, January 26, 2016
Cancer in Children
William Bunn: 8-Year-old Police Officer
July, 2010
Filename: BoyPoliceman11July10.doc
http://abclocal.go.com/wtvd/story?section=news/local&id=7531763
- 2 minutes and 32 seconds
(Link goes to text story. Video link may have been discontinued)
Refers to Stem Cell Transplants and Chemotherapy for
neuroblastoma
Kelley Mitchell: By Jim Lehrer, The News Hour
Cancer and Other Causes of Death in Children
Number of Children
0 to 5 Years Old:
6 to 11 Years Old
12 to 17 Yrs Old
25.7 Million
25.0 Million
25.4 Million
Cancer Deaths in Children
140 children per million children/year
75 Million Children = 10,500 Cancer Deaths per Year
1.8 % of total Cancer Deaths per Year
Gun Deaths in Children Ages 0 to 14 per Year:
3,400 Gun Deaths per Year
(Accidental and Deliberate Homicide)
School Shootings per Year Tripled since 1995
Sharpton News; January 16, 2013
116,000 Guns Deaths in Children since 1979
Comparison of Gun Deaths per 100,000 population; nine countries
http://www.gunpolicy.org/firearms/compare/66/rate_of_gun_homicide/10,39,
57,69,82,88,91,194
The Next Four Slides are Turning Point Quiz Questions
You may not use any notes or electronic devices other than
your NXT transmitter. No computers. No phones. No talking or
consulting.
Make sure that your desk is clear.
These are graded quizzes that make up 40% of the overall
course grade.
They are designed for both you and me to determine whether
you are paying attention and following what is going on.
Response
Counter
Response
Counter
Response
Counter
Response
Counter
How This Course in Cancer Biology is Set Up
Part 1: What is Cancer like as a collection of diseases?
(Topics: Intro501; Clinical Patterns, Epidemiology, Classifications,
Model Systems)
Part 2: How do Cancers get that way?
(Topics: Cancer Cell Properties, Cancer Cell Interactions, Progression,
Growth, Invasion and Metastasis, Cancer Genetics, Cancer Virology)
Part 3: What can we do about it?
(Topics: War on cancer 1972-2015, Cancer Therapy, Cancer Immunology,
Immunotherapy of Cancer; Clinical Management
Why Study the Biology of Cancer?
Biology as the Basis For:
Improved Diagnosis
Improved Management
Increased Survival Time
Long-Term Cures
Prevention
Chance for cure or extended survival
depends strongly on where patient goes for
diagnosis and where patient is treated!
(See Newsweek, Oct. 26, 2009)
“What You Don’t Know Might Kill You,
Why Biology of Cancer Now? The Knowledge Base
Advances in Molecular Genetics
• Genomics and Proteonomics
Cellular and Humoral Immunity
Inter-cellular Communication and Regulation
• Cytokines, Growth Factors, Receptors
Membrane Structure and Function
• Membrane Adhesion Receptors and Ligands
• Membrane Transport
Intra-cellular Pathways and Regulatory Cascades
• Cell Cycle Control
• Regulation of Nuclear Gene Expression
• Normal and Aberrant Differentiation
• Pathways to Cell Death or to Cellular Immortalization
Virology and Bacteriology
Infectious disease patterns, immune response and escape
Biotechnology & the Cancer Problem
the Technological Tools Now Available
Genetics, Cell, and Molecular Biology
• Gene Identification, Isolation, Cloning, & Sequencing
• Structure, Relationships, & Functions of Gene Products
• Directed Protein Synthesis, Site-Directed Mutagensis
Cell Separation and Cell Culture
• In Situ Cell Labelling and Dynamic Functions
• Cellular and Humoral Immunity
• Monoclonal Antibodies
• Radio-immunoassays
• In Situ Labelling and Diagnosis
• Flow Cytometry and Cell Sorting
Biophysical Tools
• Magnetic Resonance, CAT Scan, X-Ray
• Radio-isotope Labelling
• Electron Microscopy
Live Animal Models and Tumor Model Systems
• Inbred Animals
• Genetically Engineered Animals
Molecular and Cellular Anomalies
in Cancer
Abberant Genes and Gene
Expression
Banding
pattern of
normal
metaphase
human
chromosomes
Figure 1.11a The Biology of Cancer (© Garland Science 2007)
Aneuploidy in Human Hepatocellular Carcinoma Cell Line
Figure 1.12a The Biology of Cancer (© Garland Science 2007)
Hsr = homogeneously staining region due to
endoreduplication of chromosomal segments
resulting in gene amplification
Fluorescent in
situ
hybridization
(FISH) of
normal
metaphase
human
chromosomes
using
chromosome
specific DNA
probes with
different
fluorescent
dyes
Figure 1.11b The Biology of Cancer (© Garland Science 2007)
Aneuploid
karyotype of
human breast
cancer cell.
Note
“scrambling” of
colors
demonstrating
chromosomal
reciprocal
translocations
Figure 1.11c The Biology of Cancer (© Garland Science 2007)
Intrachromosonal
inversion by
M-band
fluorescent
in situ
hybridization
(mFISH)
Figure 1.11d The Biology of Cancer (© Garland Science 2007)
Gene Expression DNA
Array Analysis
mRNA’s From
142 different
human tumors
Red =
elevated
expression
1800
Human
Genes
Green =
diminished
expression
Figure 1.18 The Biology of Cancer (© Garland Science 2007)
Molecular and Cellular Anomalies
in Cancer
Abberant Genes and Gene Expression
Aberrant Cell Structures
and Cell Behavior
Role of the Cytoskeleton
in Cell Adhesion, Cell Division,
Cell Migration
Cytoskeleton:
Actin
microfilaments
Microtubules
Intermediate
filaments
Figure 1.14a The Biology of Cancer (© Garland Science 2007)
Intermediate
Filaments of
epithelial cell
(keratin) in
green
Plasma
membrane
in blue
Figure 1.14b The Biology of Cancer (© Garland Science 2007)
3T3 Mouse
Fibroblast
attached to
fibronectin
extracellular
matrix by
integrin
receptors
Figure 1.14d The Biology of Cancer (© Garland Science 2007)
Motility of a Fish Keratocyte
Actin microfilament leading edge
To Here, Thursday, January 21, 2016, Class 2
Figure 1.15c The Biology of Cancer (© Garland Science 2007)
Why is Cancer This Way?
What can we do about it?
The Complexity of
Signaling Factors,
Receptors, and Pathways
Growth Factors and Receptors:
Signal Transduction Across Membranes
Ras Pathway
Growth Factors
PMA
GAP
GTP
GRB2
SOS
P
CD-GEGII
Ras
GEF
GDP
P
P
Ras
PLC-ε
p120GAP
PI3K
RalGDS
P
Raf
Rac
Rap1A
p190-B
Ral
GTP
P
MEKs
PAKs
PLD
RalBP1
Rho
PLD
Pathway
MEKK1
ERKs
CDC42
P
Stress Fibers and
Focal Adhesions
JNKK
ERKs
JNK
JNK
Elk1
c-Jun
ATF2
Gene
Expression
c-Fos
2009
ProteinLounge.com
C
Pathways in Human Cancer
Garland Publishing
Companion Piece to The
Biology of Cancer
www.cellsignal.com/CSTcancer
See Tumor Immunology
Apoptosis
Approaches to Cancer Management and
the Problem of Cost and Availability
New Cancer Chemotherapy Developments
Revlimid (Lenalidomide)
Revlimid Costs and Cancer Treatment
•Revlimid is used in treatment of Multiple Myeloma, Mantle Cell Lymphoma (MCL),
transfusion-dependent myelodysplastic syndrome (MDS).
http://www.goodrx.com/revlimid?gclid=COXHoJHvj8MCFeVj7AodmXgAiQ
The Next Two Slides are Turning Point Quiz Questions
You may not use any notes or electronic devices other than
your NXT transmitter. No computers. No phones. No talking
or consulting.
Make sure that your desk is clear.
These are graded quizzes that make up 40% of the overall
course grade.
They are designed for both you and me to determine whether
you are paying attention and following what is going on.
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Intro501 Stops Here for 2016
Go to: Cancer2013_ACS.pptx
American Cancer Society Facts and Figures for 2014
On a scale of 1 to 5 rate:
#1 = -2 = I’m pretty much lost, Please slow down and repeat.
#2 = -1 = I’m struggling. I follow some of it, but I’m having hard time.
#3 = 0 = I’m OK. I understand most of it. I’ll figure the rest out later.
#4 =+1 = I doing OK. No Problem.
#5 = +2 = This is no sweat. Please get moving before I get totally bored.
5
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1
Duration: 0 Seconds
Gene Cloning in a
Bacterial Vector
Figure 1.21 The Biology of Cancer (© Garland Science 2007)
Regulation of Gene Expression by Transcription Factors:
General and Specialized Transcription Factors
Figure 1.19 The Biology of Cancer (© Garland Science 2007)
Molecular Signaling in Cancer (From Quigen.com)
Cancer Biology and Clinical Treatment
The Impact of the Health-care System
About Kuyler Van Nocker
and
Neuroblastoma
Week Two: The Story of Kelley Mitchell and Ewings Sarcoma
Cancer Treatment | PBS NewsHour |
Jan. 1, 2001 | PBS
Jan 1, 2001 ... ELIZABETH
BRACKETT: Last year, Kelley
Mitchell lost her battle against cancer.
But before the 16-year-old died, she
agreed to try a highly ...
www.pbs.org/newshour/bb/health/jan-j
une01/cancer_01-01.html
Link to video no longer active.
Will attempt to display some of these stories in class from DVD’s