Download Model Systems in Cancer Biology and Cancer Medicine

Model Systems in Cancer
Biology and Cancer Medicine
Folder Title: Models(NoTP)
Updated: February 14, 2017
Studying the Basic Biology of "Cancer"
Generalizations About "Cancer"
Model Systems and Research Objectives:
What Do We Want to Know?
• 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
•
•
•
•
•
•
IP (Intraperitoneal)
SC (Sub-cutaneous)
IM (Intra-Muscular)
ID (Intra-dermal)
IV (Intravenous)
IT (Intra-thecal) (Spinal column or brain)
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 13
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
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
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
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
External Malignant
Melanoma on
Xiphophorus Hybrid
XiHiTumor
Melanoma in Hybrid Tropical Fish
(from Cancer Research, January 1, 1995)
NodMel
The Ugly Truth of Pediatric Cancer
Stories of Childhood Cancer
www.youtube.com/watch?v=7T3zQmBojAU
Uploaded by KidsCancerChannel
This video shows the ugly side of pediatric cancer, and just a glimpse into the
... Ava's Cancer Storyby ...
More videos for The Ugly Story of Pediatric Cancer »
Note: You may want to dispute the use of the word “Ugly” by those who
compiled this montage of children with cancer. There is crushing sadness and
heartache, but much of beauty shared by the children, their parents, and their
brothers and sisters.
Check out Ava’s Story
See story on “Childhood Cancer is Not Rare
The Next Three 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.
Response
Counter
We will save the current Turning Point
Quiz Results
Then we will switch to anonymous so
you can tell how the course is going
without our knowing what individual
students said about how the course is
for them.
For the first third of BIO 501
(This poll is anonymous. I won’t know
who you are.
I am resetting the Turning Point System to Anonymous)
First-rate
Really good, I’m pleased
About Average
Pretty Poor. I’m disappointed
Terrible.
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Models presentation ended here:
Tuesday, February 14, 2017
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Human Patients as Cancer Models:
Glioblastoma Multiforme Duke University
Dr. Henry Friedman, 2010
Henry Friedman and Glioblastoma Multiforme
Death of Senator Edward “Ted” Kennedy
YouTubeFriedman2010.doc
http://www.youtube.com/watch?v=n1Z8yMxSf5E
Too Much of Henry Friedman again, but go to the site.
Many links to Brain cancer appear to the right.
Choose ones of interest.
Audio does not come up in class. Try on you own computer
Dark Pigmentation, No External Tumor
Xiphophorus Hybrid
DarkXiHi