bio 501 the biology of cancer introduction to 501 online: intro501(notp) updated: january 10, 2015
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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 CultureTransformed Normal CellsFreshly-derived Cancer CellsGenetically Engineered CellsEngineered Tissues (3-Dimensional Cell Cultures)Animal Models in Cancer Research and Cancer Medicine
(“Pre-Clinical Trials”)Inbred Animal ModelsVeterinary AnimalsAnimal-Human Engineered Hybrid Models
Clinical Cancer in PatientsClinical 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 CultureHow 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 CancersHow 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 NeuroblastomaSee UntreedReads.comDaydreams 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 ImmunogenicityCellular Senescence, Immortalization, and Cancer
Cell Death (Genetically-programmed cell death; Apoptosis)Telomeres and Cell Ageing
Autophagy (Inter-cellular “cannibalism”) and CancerIntra-cellular signaling
Growth Factors and ReceptorsInter-cellular Communication
Cell MovementGene Expression and Differentiation Control
Normal Immune Responses and Immune EscapeProtein 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 ManagementSpecific 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?
To Enter your name on your NXT Transmitter(Revised January 10, 2015)
For NXT Transmitter (Off-white)Press grey button with white oval in the middle
Get screen with a wrench on itPress 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: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.
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 card that you filled out on the date when you borrowed our transmitter. Do not change the “BIO” designation.
3. We are using Channel 41 in this room. NXT should find Channel 41 when you hit “Find Channel”. You get a smiley face.
4. Respond to the question 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. 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.
8. 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.
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
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:
I am here!
1. 2.
0%0%
1. Yes
2. No
Response
Counter
Course Evaluation, Grading,and Maintenance of Standards
Three In-Class Exams, 100 Pts EachTuesday 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-SiteIntegrated 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. WeinbergGarland 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 BiologyGeneticsMolecular BiologyBiochemistryImmunologyMicrobiology/VirologyDevelopmental BiologyPhysiologyEnvironmental Biology
HistologyPathobiologyPharmacologyEpidemiologyNeurobiologyOrganic ChemistryPhysicsStatisticsComputer 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• 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 OfficerJuly, 2010Filename: BoyPoliceman11July10.doc Video 1http://abclocal.go.com/wtvd/story?section=news/local&id=7531763 - 2 minutes and 32 seconds Video 2http://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: 25.7 Million6 to 11 Years Old 25.0 Million12 to 17 Yrs Old 25.4 Million
Cancer Deaths in Children 140 per million children/year75 Million Children = 10,500 Cancer Deaths per Year1.8 % 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, 2013116,000 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 ManagementIncreased Survival Time
Long-Term CuresPrevention
Chance for cure or extended survivaldepends 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 ProteonomicsCellular and Humoral ImmunityInter-cellular Communication and Regulation• Cytokines, Growth Factors, ReceptorsMembrane Structure and Function• Membrane Adhesion Receptors and Ligands• Membrane TransportIntra-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 Problemthe 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 MutagensisCell Separation and Cell Culture• In Situ Cell Labelling and Dynamic Functions• Cellular and Humoral Immunity• Monoclonal Antibodies• Radio-immunoassays• In Situ Labelling and DiagnosisBiophysical Tools• Magnetic Resonance, CAT Scan, X-Ray• Radio-isotope Labelling• Electron MicroscopyLive Animal Models and Tumor Model Systems• Inbred Animals• Genetically Engineered Animals BioTools
Figure 1.11a The Biology of Cancer (© Garland Science 2007)
Banding pattern of normal metaphase human chromosomes
Figure 1.11b 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 1.12a The Biology of Cancer (© Garland Science 2007)
Aneuploidy in Human Hepatocellular Carcinoma Cell Line
Hsr = homogeneously staining region due to endoreduplication of chromosomal segments resulting in gene amplification
Figure 1.11c The Biology of Cancer (© Garland Science 2007)
Aneuploid karyotype of human breast cancer cell.
Note “scrambling” of colors demonstrating chromosomal reciprocal translocations
Figure 1.11d The Biology of Cancer (© Garland Science 2007)
Intra-chromosonal inversion by M-band fluorescent in situ hybridization(mFISH)
Figure 1.18 The Biology of Cancer (© Garland Science 2007)
1800 HumanGenes
mRNA’s From 142 different human tumors
Red = elevated expression
Green = diminished expression
Gene Expression DNA Array Analysis
Molecular and Cellular Anomalies in Cancer
Aberrant Cell Structures and Cell Behavior
Role of the CytoskeletonIn Cell Adhesion, Cell Division, Cell
Migration
Figure 1.14a The Biology of Cancer (© Garland Science 2007)
Cytoskeleton:
Actin microfilaments
Microtubules
Intermediate filaments
Figure 1.14b The Biology of Cancer (© Garland Science 2007)
Intermediate Filaments of epithelial cell (keratin) in green
Plasma membrane in blue
Figure 1.14d The Biology of Cancer (© Garland Science 2007)
3T3 Mouse Fibroblast attached to fibronectin extra-cellular matrix by integrin receptors
Figure 1.15c The Biology of Cancer (© Garland Science 2007)
Motility of a Fish Keratocyte
Actin microfilament leading edge
Why is Cancer This Way?
What can we do about it?
The Complexity of Signaling Factors, Receptors, and
Pathways
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T
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Ras Pathway
SHC
GDP
GTP CD-GEGIIGAP
GTP
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PP P
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Stress Fibers and Focal AdhesionsStress Fibers and Focal Adhesions
GeneExpression
GeneExpression
PLDPathway
PLDPathway
PMAPMA
Growth FactorsGrowth FactorsIncreased T Cell
AdhesionIncreased T Cell
Adhesion
IntegrinsIntegrins
β1β1β2β2 β2β2
β1β1β1β1SOS
p120-GAP
p190-B
Rho
PI3KPLC-ε
Rap1A
PLD RalBP1
PAKs
ERKs
ERKs
JNKK
JNKJNK
MEKK1
CDC42
Rac
MEKs
RafRalGDS
Ral
GRB2
TC
R
TC
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AntigenAntigen
LckGEF
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2009ProteinLounge.com 2009ProteinLounge.com
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Growth Factors and Receptors:Signal Transduction Across Membranes
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.
About Kuyler Van Nocker
and
Neuroblastoma
http://www.msnbc.msn.com/id/3036677/#39049661
Cancer Biology and Clinical TreatmentThe Impact of the Health-care System
Cancer Treatment | PBS NewsHour | Jan. 1, 2001 | PBSJan 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-june01/cancer_01-01.html
Week Two: The Story of Kelley Mitchell and Ewings Sarcoma
Last Presentation: The Story of Taylor Black and Neuroblastoma(“Daydreams and Diaries” - UntreedReads.comOnLine 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.
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Duration: 5 Seconds
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