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43 Cards in this Set

  • Front
  • Back
neoplastic transformation
chemical carcinogens
radiant energy
oncogenic viruses and microbes
chemical carcinogenesis
initiation, promotion, progression
initiation
rapid, irreversible, memory
permanent damage to DNA of target
promoters
can induce tumors in initiated cells, but are nontumorigenic by themselves. effect is reversible, does not affect DNA
complete carcinogen
chemicals that are both initiators and promoters
incomplete carcinogen
chemicals that are capable of initiation
direct acting carcinogens
do not require chemical transformation
indirect acting or procarcinogen
require metabolic conversion to the ultimate carcinogen
what gene mutation is common in chemically induced tumors?
Ras gene
most widely used tumor promotor of carcinogenesis?
TPA--activator of protein kinase C,which results in proliferation and modulates differentiation
alkylating agents
direct acting carcinogens
anti-cancer drugs
acylating agents
direct acting carcinogens
do not need metabolic conversion and are weak carcinogens; many are therapeutic agents, act by interacting with and damaging DNA
procarcinogens
polycyclic and heterocyclic aromatic hydrocarbons
aromatic arimes, amides, and azo dyes
naturally occuring carcinogens
nitrosamines and amides
formed in GI tract and implicated in gastric carcinoma, caused by conversion of bacteria of nitrates and nitrostable amines to nitrites
asbestos
lung cancer, mesotheliomas, GI cancers
vinyl chloride
hemangiosarcoma of liver
plastic factory, then mass in liver;
chromium, nickel, and metals
volatized and inhaled causes lung cancer
saccharin
cancer in rats
hormones (estrogen)
endometiral cancer in post menopausal women
effects of UV light on cells
inhibition of cell division, inactivation of enzymes, induction of mutation, cell death
XP
AR disorder with defect in the NER of DNA, photosensitivity, and 2000x increase risk of skin cancer
xrays
skin cancer
miners of radioactive elements
lung cancer x 10
atom bomb
leukemia, breast, thyroid, lung, colon
therapeutic radiation
carcinogenic. thyroid cancer in 9% of those exposed to head and neck radiation
DNA oncogenic viruses
HPV, EBV, HBV, KSHV
HPV
70 subtypes; types 1,2,4 and 7 for benign squamous papillomas (warts); SCC of cervix and anogenital region--types 16 and 18; less frequently 31, 33.**
genital warts-- 6 and 11
E7 binds pRb; E6 binds p53.
EBV
herbes; Burkitt's lymphoma; B cell lymphoma in immunocompromised; hodgkin lymphoma, nasopharyngeal carcinoma
EBV induced Burkitt's
infects nasopharynx epithelial cells and B lymphocytes via CD21 receptors; infxn of B cell is latent; actively dividing cells are at increased risk for mutation; t(8;14); 80% carry this translocation; 100% of nasopharyngeal carcinomas have EBV DNA
HBV
strong assoc with hepatocellular ca; endemic in far east and africa; HBV genome does not encode any oncoproteins and the pattern of integration is not constant; effect of HBV is indirect and multifactorial; liver injury and regenerative hyperplasia increase risk for genetic mutation
HTLV-1
assoc with T cell leukemia/lymphomas; endemic in japan and caribbean; sporadic in US; trophism for CD4+ T cells, which are target for neoplastic transformation; infected T cells transmitted by sex, blood products, and breast feeding. leukemia in 1% of infected; causes demyelinating neuro disorder
helicobacter pylori
causes gastric lymphomas (B cell)/MALTomas/marginal zone lymphomas more frequently than gastric carcinomas
3 factors determining growth of tumor
1. doubling time of tumor cells
2. fraction of tumor cells in replicative pool
3. rate at which the cells are shed or lost
GF
proportion of cells in proliferative pool; in fast growing tumors, 20% or less; high cell turnover, increased production, and apoptosis; effect on susceptibility to chemo; also correlates with level of differentiation
prognostic indicator correlating with malignancy?
extent of angiogenesis; vessel density is prognostic indicator
most important angiogenic factors?
VEGF and bFGF
elevated in serum and urine of many cancer patients
tumor cells may also produce anti-angiogenic factors like thrombospondin 1.
angiostatin, endostatin, and vasculostatin
angiogenesis inhibitors derived by proteolytic cleavage of plasminogen, collagen, and transthyretin
invasion of ECM
detachment of tumor cells from each other
attachment to matrix components
degradation of ECM
migration of tumor cells
E cadherin
transmembrane glycoprotein that is important adhesion molecule; linked by catenins, which lie under the plama membrane; downregulated in many tumors; fxn dependent on linkage to catenin. in some tumors, there is mutation in gene for catenin which reduces expression of Ecadheri
attachment to ECM
tumors with increased laminin receptors and integrins show increased ability to invade and metastasize
receptor mediated attachment to laminin and fibronectin
degradation of ECM
serine, cysteine, and matrix metalloproteinases
migration mediated by:
1. tumor cell-derived motility factor
2. cleavage products of matrix compounds (collagen and laminin)
tumor antigens
TSA on tumor cells; TAA on tumor cells and some normal cells; TSA evoke cytotoxic T cell response; present within tumor cells on MHC I molecules