Term
Is carcinogenesis usually somatic or germline? |
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Definition
Somatic--due to multi-step changes in oncogenes, tumor-suppressor genes, or apoptosis defects
single genetic change is rarely enough to induce CA--exception Rb/Retinoblastoma
loss of suppression is more common and usually worse than gain of activation |
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Term
Germline mutations
-age
-uni/bilateral
-# tumor types
-risk factors
-other sx |
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Definition
young age
bilateral
multiple tumor types
often family history
syndromic (constellation of seemingly unrelated sx) |
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Term
aberrant behavior of almost-normal cells, disrespect for boundaries, ectopic growth, angiogenesis |
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Definition
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Term
Knudson's Two Hit Hypothesis |
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Definition
cancer is usually result of accumulated mutations (genetic, spontaneous etc)
explains why genetic cancers often earlier onset (1st hit already present at birth) |
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Term
Non-genetic risks for cancer |
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Definition
radiation, infections (HPV, HIV, HCV, HHV-8, H Pylori), chemo, defect in detoxifying enz, atomic bombs, diet, environment, prolonged exposure to hormones (ex: estrogen) |
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Term
cancer and the immune system |
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Definition
important link--immune system plays important role in surveillance for and elimination of cancerous/precancerous cells
immune dysfunction associated with higher cancer risk, esp leukemias and lymphomas |
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Term
cancer and chromosomal instability |
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Definition
those with diseases that cause chromosomal instability (mutations in DNA repair enzymes, etc) are at a much higher risk for developing cancer |
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Term
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Definition
transcription factors
tyrosine kinase activity
chromatin remodelers
growth factors |
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Term
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Definition
chronic myelogenous leukemia
due to translocation between chrom 9 and 22 (Philadelphia chromosome)-->bcr-abl protein
results in removal of inhibition of tyrosine kinase-->uncontrolled proliferation
treated with Imatinib, ABL inhibitor |
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Term
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Definition
asymmetric methylation leading to unilateral expression of a single allele
ex: paternal expression of IGF2 and maternal expression of H19 is common
loss of heterozygosity/imprinting-->down-reg of H19 (inhibits IGF2) "uniparental disomy"-->growth factor over-production-->wilm's tumor |
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Term
suppressor-oncogene relationship |
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Definition
suppressors>oncogenes
loss of suppressor=BAD NEWS
oncogene overexpression-->cancer |
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Term
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Definition
tumor grows own blood supply-->very pathologic
CANCER
anti-angiogenic therapy (ex: thalidamide) |
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Term
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Definition
embryology--regulated growth
cancer--dysregulated growth
embryologic defects and large chrom changes freq assoc w cancer |
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