Neoplasia V Flashcards
what cancer is associated with APC? how?
familial polyposis coli (adenocarcinoma of colon)
what cancer is associated with BRCA 1/2?
breast and ovarian
what cancer is associated with RB?
retinoblastoma and osteogenic sarcoma
what is the function of APC?
prevents nuclear transcription
what is the function of BRCA 1/2?
regulates DNA repair
what is the function of RB?
inhibits G1 - S phase
what is the role of the WNT pathway?
- controls cell fate, adhesion, and cell polarity during embryonic development 2. self-renewal of hematopoietic stem cells
what happens following a double mutation in APC?
B-catenin accumulates in cell - FAP, non-familial colorectal CA and sporadic adenomas
what are the cancer associated with RB mutations?
retinoblastoma, osteosarcoma, soft tissue sarcoma
what is the function of p53?
inhibits G1 - S phase, repairs DNA, activates BAX
what cancers are associated with p53 mutation?
lung, colon, breast CA, Li Fraumeni syndrome
which HPV protein inhibits p53?
E6
what is the VHL gene?
tumor suppressor gene on chromosome 3 - part of ubiquitin ligase complex
what is the role of the VHL gene?
regulates nuclear transcription via HIF-1a
what diseases are associated with VHL mutations?
hereditary renal cell CAs, pheochromocytomas, hemangioblastomas of CNS, retinal angiomas, renal cysts
What is the Warburg Effect?
cancer cell preference for aerobic glycolysis, glucose uptake; tumors are detectable by PET
how do carcinogens act?
highly reactive electrophiles - remove electrons from DNA / RNA / proteins - cause cell damage directly (without modification) or indirectly (require metabolic activation)
is permanent DNA damage accomplished during the initiation or promotion phase of carcinogenesis?
initiation
is the initiation phase of carcinogenesis reversible or irreversible?
irreversible (and rapid)
does the promotion phase of carciniogenesis affect DNA? is it reversible or irreversible?
- no 2. reversible
what are the chemical involve in the initiation phase of carciniogenesis?
attack electron rich areas of cell (eg DNA) - chlorambucil, busulfan, melphalan
most carcinogens are metabolized by what enzymes?
p450 dependent monooxygenases
B-naphthylamine is associated with what type of cancer?
bladder
what is the effect of aflatoxin B1?
- potent hepatic carcinogen, causes p53 mutations and hepatocellular CA 2. mycotoxin produced by fungus aspergillus flavus (improperly stored rice, corn, peanuts)
what type of cancer is associated with nitrosamines and amines?
gastric CA (converted to nitrites by bacteria)
estrogen is a promoter of what type of tumor?
liver tumor
diethyl stilbesterol is a promoter of what type of cancer?
post-menopausal endometrial CA, vaginal cancer
high dietary bile acids are promoters of what type of cancer?
colon CA
