FINAL EXAM
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15-25% OF CANCER is caused my a virus. what exp proved this
russian scientist - big chunks of tumors being transferred to puppy and them ending up with cancer too
How did Peyton Rous virus cause sarcoma in chicken?
he induced sarcomas in chickens 1. removed sarcoma from a chickens breast 2. grind sarcoma with sandpaper 3. collect filtrate 4. inject filtrate into young chickens and observe agrees with Russian scientist (dog exp) that tumors can cause more tumours
Nude mice
kept in sanitary conditions, have no hair & no immune system; used as animal models to grow literally anything
howard temin experiment 1
Experiment: Control w/o RSV didn’t grow, while RSV-infected cells grew in soft agar! Temin took RSV transformed cells & injected them into nude mice; in 2-3 weeks, tumors formed. Temin is convinced that RSV causes sarcomas/cancer no one wanted to claim a causation between viruses & cancer except Temin (fear from Fibige fiasco)
Temin’s 2nd experiment
RSV that was temperature sensitive (proteins denature & destroy enzyme so the virus becomes non functional) normal cell+ mutant rsv (at permissible temp) = rna turns to dna normal cell+mutant rsv (non-permissable temp)= cells stayed non transformed Temin finds reverse transcriptase (RT) Baltimore corroborates conc- viruses cause sarcoma
Normal & transformed cells properties
Healthy cells: no contact, uniform, flat, organized (normal cellular equilibrium) Transformed / sick cells: no contact inhibition (overlapping cell borders), no cell function, chaos!
Anchorage-independent growth on soft agar
need solid surface bc of anchorage dependency - protein of cell needs to bind to solid surface to survive Normal cells do not grow on soft gel-like surfaces (like gel matrix) So it can be inferred that if cells grow in soft agar they are transformed cells!
Properties of transformed cells looks alot like hallmarks of cancer
• Altered morphology • ability to grow w/o attachment • ability to proliferate indefinitely, 4. high saturation density, • grow over each other • increased transport of glucose.
Michael Bishop & Harold Varmus why rsv causes cancer
RSV = transformative, eventual cancer ALV = no transformation, no cancer
how does a proto-oncogene become an oncogene
Normal src is ok (a proto-oncogene) but the promoter in front of src generates a billion copies & causes it to become an oncogene RSV w/o src = harmless RSV w src = cancer
why do viruses cause cancer
• Extremely strong promoter (make lots of copies) • Cause mutation
Myc proto-oncogene in front of genes,
can become oncogenic & cause abnormal cell proliferation
Retrovirus discovery led to three further ideas:
• If retroviruses could activate a proto oncogene into a potent oncogene, perhaps other types of mutational mechanisms. • Clear that all transforming powers of RSV derived from presence of single gene • Perhaps other transforming retroviruses had acquired other cellular genes unrelated to src
Kinase Activity of Src
1.Src is an enzyme- Controls cell pathways, proliferation, apoptosis, etc 2. Bishop & Varmus found src phosphorylated antibodies - bind to src, phosphorylate (add phosphate on kinase)
viral inactivation of p53
SV 40= stabilises p53 inactive state HPV= triggers degradation of p53 Adeno e1b= blocks transcriptional activation function
FISH-
test done to check how many copies of myc genes. (take a probe on an antibody over the tumor and then over the normal cells, The intensity is the determinant.
Translocation of myc oncogene-
through BFB you have a potential of a strong promoter being joint to a proto-oncogene which can cause lymphoma.
Hepatocellular carcinoma
• protein in HBV makes p53 inactive • inflamation causes necrosis and then replaced by very mutated cell 3.oxidative stress= too many free radicals=genetic alteration 4.drinker, smokers more prone
HPV
HPV type 16,18 are called ‘high risk’ as they can lead to cervical cancer. HPV can cause head and neck cancer (oral sex) and vaginal, cervical, anal and penile (sex) Prevention: abstinence, condoms, vaccines and microbiotics
How does HPV cause cancer
• hairline crack in the cervix. Through this crack the virus gets inside the cells and becomes an episome • The viruses urge the cell to proliferate • E6 will specifically bind to p53 and E7 will bind to pRB (tumor suppressor and helps regulate cell cycle.) • cell begins proliferating abnormally as it is now unchecked. This is a vicious cycle as it keeps infecting and proliferating. It then becomes hyperplastic and mildly dysplastic.
CIN 1,2,3? Cervical Intraepithelial neoplasia)
CIN 1- Cervical Intraepithelial neoplasia, reversable (grade 1) CIN 2- reversible till a certain point by an epithelial lavage (grade 2) CIN 3- full blown carcinoma of the cervix, irreversible, is metastatic if it passed the basement membrane (grade 3)
Gardasil story (HPV Vaccine)
Dr. Doug Lowy said he didn’t want the offered 400 million in royalties but instead wanted the vaccine to be very cheap and accessible and to therefore save as many lives as possible. reduction in genital warts and prevent throat cancer
reason high fructose corn syrup is used
Inexpensive, addictive and abundant, partially due to corn subsidies in the United States.
leptin and leptin resistance
Leptin lets your brain know whether it is full or not. However, too many fat cells= too much leptin=leptin resistance=always hungry (no fullness cues). If there is too much leptin in system the body becomes desensitised. So it craves more due to leptin resistance.