Day 8, Lecture 1 (Aug 31): Cancer III: Environment, Models, and Targeted Therapeutics Flashcards Preview

MCS > Day 8, Lecture 1 (Aug 31): Cancer III: Environment, Models, and Targeted Therapeutics > Flashcards

Flashcards in Day 8, Lecture 1 (Aug 31): Cancer III: Environment, Models, and Targeted Therapeutics Deck (35):
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Aflatoxin

  • From grain and peanuts contaminated with Aspergillus 
  • Cancer:
    • Hepatocellular carcinoma
  • Mechanism:
    • Reactive metabolite causing DNA damage

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asbestos (silicate minerals) cause what kind of cancer

  • Mesothelioma
  • mechanism:  unknown

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Cigarette smoke (contains 3,4-benzpyrene) causes what cancer and how

  • lung cancer
  • mechanism:
    • Reactive metabolite causing DNA damage

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radiation (ionizing) causes what kind of cancer and how

  • cancer:
    • leukemia, thyroid cancer
  • Mechanism:
    • mutations, genome-level breakage

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Sunlight (UV light) causes what cancer and by what mechanism

  • Cancer:
    • Carcinoma
    • Melanoma
  • Mechanism:
    • Pyrimidine dimers

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Aflatoxin leads to DNA adducts and mutation of ____

  • p53

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Human papillomavirus (HPV) causes _____ cancer

  • HPV causes cervical cancer
  • Can cause some oropharyngeal squamous cell carcinomas
  • Human Papillomavirus 
    • sexually transmitted
    • dsDNA virus
    • 40 types (of about 100) infect female GU tract
      • high-risk types such HPV 16 and 18: vervical dysplasia and cancer
      • low-risk types: condyloma (genital warts)
    • only a minority of infected women develop cervical cancer
  • Prevention: Gardasil (doesn't cover all types)

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What is dysplasia

abnormal, disorderly growth

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HPV proteins bind to what

  • HPV protein E6 binds to p53
  • HPV protein E7 binds to RB

 

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Human Herpes virus 8 (HHV-8) causes what kind of cancer

  • body cavity lymphoma
  • Kaposi Sarcoma

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Epstein-Barr virus (EBV) causes what kind of cancer

Burkitt lymphoma

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Human papilloma virus (HPV) causes what kind of cancer

Cervical carcinoma

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Hepatitis B virus (HBV) and hepatitis C virus (HCV) cause what kind of cancer

Hepatocellular carcinoma

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Colorectal carcinomas can arise in a stepwise fashion, explain 

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What is the difference between FAP (familial adenomatous) and Hereditary non-polyposis colon cancer (HNPCC/Lynch syndrome)

  • in FAP the colon is carpeted with polyps while in HNPCC the colon has a few polyps 
  • both are autosomal dominant
  • HNPCC is caused by mutations in mismatch repair genes MLHI, MSH2, MH6, and PMS2 
  • FAP is caused by mutation in APC (adenomatous polyposis coli; 5q21): tumor suppressor 
    • missense mutations and deletions 
  • FAP has 100% colorectal cancer risk at 50 years while lynch syndrome has 80% colorectal cancer risk at age 44

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What is the common treatment for FAP 

prophylactic colectomy because colorectal cancer risk is 100% at 50 years old 

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are microsatellites scattered throughout the genome 

yes 

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FAP is caused by a mutation in 

APC (5q21)

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Explain how the microsatellite instability pathway can result in colonic adenocarcinoma

  • Microsatellites have STR (short tandem repeats) these can get mismatched if the polymerase slips thus leading to a loop, which if not fixed leads to a longer allele 

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What is KRAS 

  • KRAS is a GTPase, signaling protein
  • mutated in colorectal carcinoma, pancreatic adenocarcinomas, and others
  • Colon cancer: about 50% have point mutations in KRAS
  • KRAS mutations predict decreased responsiveness to monoclonal Ab therapy against epidermal growth factor receptor (EGFR) (e.g. cetuximab, panitumumab) 
  • mutations nomrally occur when A is substituted for T in codon 61

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About half of melanomas have ____ mutations 

BRAF

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What is BRAF

  • signal transduction protein downstream of KRAS
  • About half of melanomas have BRAF mutation

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Melanomas with _______ mutation respond to BRAF kinase inhibitors such as _____

  • BRAFV600E (valine to glutamate at amino acid position 600, i.e. a missence mutation normally mutation is T to A)
  • Vemurafenib

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can mRNA be extracted from cancer and quantified

  • Yes
  • it can show the gene expression and the need for more or less aggressive therapy 

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There are how many molecular building blocks of life 

68

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What is systems biolgy

quantify systems components and group into networks 

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