BIO 501
The Biology of Cancer
Introduction to 501
Online: Intro501(NoTP)
Updated: January 10, 2015
NewsWeek
Oct. 26,
2009
Phenomenology of Cancer:
What are the features that cancers
present 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?
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 Cancer Medicine
(“Pre-Clinical Trials”)
Inbred Animal Models
Veterinary Animals
Animal-Human Engineered Hybrid Models
Clinical Cancer in Patients
Clinical Trials (Phase I, Phase II, and Phase III)
What are Cancer Cells Like?
As Isolated Cells?
In Tumor-bearing Animals?
In Patients?
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 Cancers like in Patients?
What do clinicians see?
What are they dealing with?
The Story of Kuyler Van Nocker and Neuroblastoma
(See Slide 49 for Video Link)
William Bunn: Boy Police-Officer and Neuroblastoma
(See Slide 24 for Video Link)
Kelley Mitchell and Ewing’s Sarcoma
(See Slide 50)
Taylor Black and Neuroblastoma
See UntreedReads.com
Daydreams and Diaries
By Tim Black (Taylor Black’s Father)
What Features are Seen in Cancer
Genetics?
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
Host Response Modifiers
Genetics and Cancer Management
Immunotherapy & Immunodiagnosis of Cancers
Cancer Chemotherapy
New Approaches to Cancer Management
Specific Targeted Therapy
(See Slides 42, Molecular Signaling in Cancer
& Slide 43, The RAS Pathway
for an examples of a cell signaling pathways in cancer.
“Phenotherapy” of Cancer?
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_______________________________________________________________
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To Respond to Turning Point Questions in Class:
Using the NXT Transmitter
(Revised January 10, 2015
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
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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
The Next Two 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 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.
You can send a “Response to Leader” while a TP Slide is
open. Give it a try. You can communicate with me.
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:
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Course Evaluation, Grading,
and Maintenance of Standards
Three In-Class Exams, 100 Pts Each
Tuesday February 17th, After Classes 1 to 10
Tuesday, March 31st, After Classes 11 to 19
Tuesday April 28th, after Classes 20 to 27
(Last Day of Class)
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
To Send in a “Response to Leader” Question at any
time during class:
Use Cntrl F8.
(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
501Text
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
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?
Improved Diagnosis, Management, and Cures?
What Do Terms in Oncology Mean?
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
•
•
•
•
•
•
•
•
•
•
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1,638,910 New Cases 2012- US; 1,660,290 (2013); 1,665,540 (2014)
~12,000,000 New Cases per Year - World-Wide
580,350 Deaths 2013- US ; 585,720 (2014)
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) will present 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 2014 (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)
Cancer in Children
William Bunn: 8-Year-old Police Officer
July, 2010
Filename: BoyPoliceman11July10.doc
Video 1
http://abclocal.go.com/wtvd/story?section=news/local&id=7531763
- 2 minutes and 32 seconds
Video 2
http://www.msnbc.msn.com/id/26184891/vp/38084943#38084943
1 1/2 minutes - actual funeral
Refers to Stem Cell Transplants and Chemotherapy for
Neuroblastoma in final 5 seconds of clip
Video 3: Kuyler Van Nocker and Neuroblastoma (Slide 49)
http://www.msnbc.msn.com/id/3036677/#39049661
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 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
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 1972-2014, 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
BioKnow
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
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
BioTools
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)
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)
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
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
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
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
Molecular Signaling in Cancer (From Quigen.com)
Thoughts on
Conversations in a
Crowded Room
The Next Two 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 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.
You can send a “Response to Leader” while a TP Slide is
open. Give it a try. You can communicate with me.
Cancer Biology and Clinical Treatment
The Impact of the Health-care System
About Kuyler Van Nocker
and
Neuroblastoma
http://www.msnbc.msn.com/id/3036677/#39049661
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
Last Presentation: The Story of Taylor Black and Neuroblastoma
(“Daydreams and Diaries” - UntreedReads.com
OnLine Story of Taylor Black by Tim Black)
Intro501 Stops Here for 2014
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
4
3
2
1
Duration: 5 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)