model systems in cancer biology and cancer medicine updated: february 7, 2013 folder title: models
TRANSCRIPT
![Page 1: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/1.jpg)
Model Systems in Cancer Biology and Cancer Medicine
Updated: February 7, 2013
Folder Title: Models
![Page 2: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/2.jpg)
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
![Page 3: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/3.jpg)
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
![Page 4: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/4.jpg)
Animal Tumor Models in VivoSource 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
![Page 5: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/5.jpg)
Tumor Models (Animal and Plant) in VivoHost Species
Mice (Inbred Strains)
Rats, Hamsters, Guinea Pigs
Rabbits
Fish
Cancers in Veterinary Animals
Cancers in the Wild
Animals
Plants
![Page 6: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/6.jpg)
Animal Tumor Models in VivoRoutes of Challenge
• IP (Intraperitoneal)
• SC (Sub-cutaneous)
• IM (Intra-Muscular)
• ID (Intra-dermal)
• IV (Intravenous)
• IT (Intra-thecal)
• PO (Orally)
![Page 7: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/7.jpg)
Animal Models in Cancer ChemotherapyNon-Mammalian ModelsMammalian Models:• Mice and Rats• Hamsters• Guinea PigsStrengths• 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 StrainsProblems: Ethical and Others
(See Limitations in Mammalian Models, Slide 14 Later)
![Page 8: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/8.jpg)
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
![Page 9: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/9.jpg)
Clinical Human Cancers as "Model" Systems
Advantages:• The Closest "Model" to the Ultimate Goals ...The Best Model for Human Cancer• Patient Feed-back and CooperationLimitations• Unmatched, genetically unique subjects• Powerful ethical limitations• Patient Independence and Failure to Comply• Prior or Concomitant TreatmentVideo on Clinical Trials in Patients
![Page 10: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/10.jpg)
Human Cancers in Animal HostsXenogeneic 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
![Page 11: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/11.jpg)
![Page 12: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/12.jpg)
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?
0 of 102
![Page 13: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/13.jpg)
Figure 13.8 The Biology of Cancer (© Garland Science 2007) p. 539
Primary excised surgical tumor pieces
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
Comparisons of Two Primary Human Cancers vs these Cancers Propagated as Model Systems
Cancer Comparisons
![Page 14: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/14.jpg)
On the previous slide showing stained sections from primary excised tumors, tumors carried in SCID Mice, and tumors grown in mice from cell culture
transplantsWhat 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?)
0 of 102
![Page 15: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/15.jpg)
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
![Page 16: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/16.jpg)
Fish Models in Cancer Chemotherapy and In Ultra-sonic Therapy in Cancers In Live Animal
Models: Potential AdvantagesEconomic• 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
![Page 17: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/17.jpg)
Normal Speckled White Xiphophorus Hybrid
SpeckledXiHi
![Page 18: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/18.jpg)
Dark Pigmentation, No External TumorXiphophorus Hybrid
DarkXiHi
![Page 19: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/19.jpg)
External MalignantMelanoma on
Xiphophorus Hybrid
XiHiTumor
![Page 20: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/20.jpg)
Melanoma in Hybrid Tropical Fish(from Cancer Research, January 1, 1995)
NodMel
![Page 21: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/21.jpg)
Human Patients as Cancer Models:
Glioblastoma Multiforme Duke UniversityDr. Henry Friedman, 2010
YouTubeFriedman2010.dochttp://www.youtube.com/watch?v=n1Z8yMxSf5E Henry Friedman and Glioblastoma Multiforme
![Page 22: Model Systems in Cancer Biology and Cancer Medicine Updated: February 7, 2013 Folder Title: Models](https://reader035.vdocuments.us/reader035/viewer/2022062423/56649eaa5503460f94baeb2c/html5/thumbnails/22.jpg)
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, 2011http://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 CancerObesity and Medical Costs, ABSNEWS, Feb. 16, 2011ObesityABC16Feb11.doc
http://abcnews.go.com/WNT/video/obesity-crisis-threatens-health-care-system-americans-exercise-food-advice-tips-health-12935370