Model Systems in Cancer Biology and Cancer Medicine

Updated: February 7, 2013

Folder Title: Models

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 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

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

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)

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)

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 CooperationLimitations• Unmatched, genetically unique subjects• Powerful ethical limitations• Patient Independence and Failure to Comply• Prior or Concomitant TreatmentVideo on Clinical Trials in Patients

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

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

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

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?)

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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 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

Normal Speckled White Xiphophorus Hybrid

SpeckledXiHi

Dark Pigmentation, No External TumorXiphophorus Hybrid

DarkXiHi

External MalignantMelanoma on

Xiphophorus Hybrid

XiHiTumor

Melanoma in Hybrid Tropical Fish(from Cancer Research, January 1, 1995)

NodMel

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

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