Transcript Model Systems in Cancer Biology and Cancer Medicine

Model Systems in Cancer
Biology and Cancer Medicine
Folder Title: Models
Updated: February 7, 2013
Studying the Basic Biology of
"Cancer"
Generalizations About "Cancer"
Model Systems and Research Objectives
• Cell Biology and Cancer
Genetic Structure
Progression
Biochemistry
Cell Cycle Regulation
• Growth Control, Immortalization, Apoptosis
• Immunology and Cancer
• Virology and Cancer
• Cancer Chemotherapy
Cancer Model Systems In Vitro
(in Cell, Tissue, or Organ Culture)
Normal Cells in Culture
• Transformed Cells
Chemically
Virally
By Irradiation
Gene Transfection
• Neoplastic Cells from Animal Tumors
• Neoplastic Cells Cultured from Human
Cancers
Animal Tumor Models in Vivo
Source of the Tumor Challenge Cells
• Implanted Cultured Neoplastic Cells
• Transplanted from Donor Animals
Early vs Later Transplant Generations
• Induced in the Tumor-bearing Host
Animals
Spontaneous (by Genetic Selection)
Chemical, Viral, Radiation Induction
• Excised from Veterinary Animals
Tumor Models (Animal and Plant) in Vivo
Host Species
Mice (Inbred Strains)
Rats, Hamsters, Guinea Pigs
Rabbits
Fish
Cancers in Veterinary Animals
Cancers in the Wild
Animals
Plants
Animal Tumor Models in Vivo
Routes of Challenge
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IP (Intraperitoneal)
SC (Sub-cutaneous)
IM (Intra-Muscular)
ID (Intra-dermal)
IV (Intravenous)
IT (Intra-thecal)
PO (Orally)
Animal Models in Cancer Chemotherapy
Non-Mammalian Models
Mammalian Models:
• Mice and Rats
• Hamsters
• Guinea Pigs
Strengths
• Genetic and Physiological Relationship to Humans
• Immune Response Similarities to Human Responses
• Rapid Gestation
• Small Body Size
• Inbred Genetically Identical and Congenic Strains
(congenic means engineered to be immunologically
compatible)
• Transgenic and Knockout Strains
Problems: Ethical and Others
(See Limitations in Mammalian Models, Slide 14
Later)
Problems with Cultured and Transplanted
Animal and Human Tumor Models
Genetic drift between cell lines and original
host animal;
Viral or mycoplasm infection of lines;
Line mix-ups;
Genetic changes in later generation
cell lines;
Cell selection in conversion to continuous
culture line
Clinical Human Cancers as "Model" Systems
Advantages:
• The Closest "Model" to the Ultimate Goals
...The Best Model for Human Cancer
• Patient Feed-back and Cooperation
Limitations
• Unmatched, genetically unique subjects
• Powerful ethical limitations
• Patient Independence and Failure to Comply
• Prior or Concomitant Treatment
Video on Clinical Trials in Patients
Human Cancers in Animal Hosts
Xenogeneic Tumor Models
Immunologically Compromised Recipient Animals
• Athymic (Nude) Mice (weak T-cell immune response)
• NK Deficient (Beige Mice)
• SCID Mice – Severe combined immuno-deficient mice
• Immunosuppression by Irradiation or Drug Treatment
Immunologically Privileged Sites
• Hamster Cheek Pouch
• Cornea of the Eye
The previous slide shows human tumors growing in SCID Mice.
How is it possible that these human tumors will grow in mice when humans
and mice are clearly different species?
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Comparisons of Two Primary
Human Cancers vs these Cancers
Propagated as Model Systems
Primary excised surgical tumor
pieces
Cancer Comparisons
Surgical specimens after 3 to 6
months growth sub-cutaneously in
SCID Mice
Prostate and colon cancer
cell lines propagated in vitro
and implanted into SCID
mice
Figure 13.8 The Biology of Cancer (© Garland Science 2007)
p. 539
On the previous slide showing stained sections from primary excised tumors,
tumors carried in SCID Mice, and tumors grown in mice from cell culture
transplants
What is the message from these comparisons?
What is this slide telling us?
Use one word or a very concise two or three words.
What is the point in one to three words?)
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Limitations for Mammalian Models
in Cancer Chemotherapy
Economic
• Acquisition Costs
• Cage Charges (Maintenance and Disposal)
Technical
• Handling (Drug Administration)
• Addition and Removal of Therapeutic Agents
• Numbers that can be Used
• Significant Body Size (20 g for mice)
Ethical/Political
• Relationship to Humans
• Animal Welfare and Animal Rights Concerns
Fish Models in Cancer Chemotherapy and
In Ultra-sonic Therapy in Cancers In Live Animal
Models: Potential Advantages
Economic
• Very rapid, high volume breeding
• Maintenance and Disposal Costs very Low
Technical
• Drug Administration via Water - Fish Exchange
• Ultra-sonic Transmission via Water in an Immersed Target
• Sequential Addition of Multiple Agents
• Ability to Remove Drug Source
• Body Size (0.5 to 2 g)
• Digital Photographic Monitoring of External Tumor
• Genetics and Inbred Strains well-established
• Zebra Danio Genetic Sequence Done
Ethical/Political
• More readily acceptable
Normal Speckled White
Xiphophorus Hybrid
SpeckledXiHi
Dark Pigmentation, No External Tumor
Xiphophorus Hybrid
DarkXiHi
External Malignant
Melanoma on
Xiphophorus Hybrid
XiHiTumor
Melanoma in Hybrid Tropical Fish
(from Cancer Research, January 1, 1995)
NodMel
Human Patients as Cancer Models:
Glioblastoma Multiforme Duke University
Dr. Henry Friedman, 2010
YouTubeFriedman2010.doc
http://www.youtube.com/watch?v=n1Z8yMxSf5E
Henry Friedman and Glioblastoma Multiforme
Video News Item MSNBC, February 9 and 10, 2010:
Keith Olbermann on Kyler Van Nocker, Neuroblastoma, and Coverage for
Experimental Therapy in Cancer.
Played from Flash Drive (45 Megs)
Children, Cancer Therapy, and Beads, Syracuse NY, 2011
http://centralny.ynn.com/content/top_stories/537100/a-creative-way-to-cope-with-cancer/
Beads4Cx18Mar11.doc
Obesity in the United States and the Future of Disease Incidence, Including Cancer
Obesity and Medical Costs, ABSNEWS, Feb. 16, 2011
ObesityABC16Feb11.doc
http://abcnews.go.com/WNT/video/obesity-crisis-threatens-health-care-systemamericans-exercise-food-advice-tips-health-12935370