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

1
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2
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3
Q

Aflatoxin

A
  • From grain and peanuts contaminated with Aspergillus
  • Cancer:
    • Hepatocellular carcinoma
  • Mechanism:
    • Reactive metabolite causing DNA damage
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4
Q

asbestos (silicate minerals) cause what kind of cancer

A
  • Mesothelioma
  • mechanism: unknown
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5
Q

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

A
  • lung cancer
  • mechanism:
    • Reactive metabolite causing DNA damage
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6
Q

radiation (ionizing) causes what kind of cancer and how

A
  • cancer:
    • leukemia, thyroid cancer
  • Mechanism:
    • mutations, genome-level breakage
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7
Q

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

A
  • Cancer:
    • Carcinoma
    • Melanoma
  • Mechanism:
    • Pyrimidine dimers
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8
Q

Aflatoxin leads to DNA adducts and mutation of ____

A
  • p53
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9
Q

Human papillomavirus (HPV) causes _____ cancer

A
  • 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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10
Q

What is dysplasia

A

abnormal, disorderly growth

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11
Q

HPV proteins bind to what

A
  • HPV protein E6 binds to p53
  • HPV protein E7 binds to RB
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12
Q

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

A
  • body cavity lymphoma
  • Kaposi Sarcoma
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13
Q

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

A

Burkitt lymphoma

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14
Q

Human papilloma virus (HPV) causes what kind of cancer

A

Cervical carcinoma

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15
Q

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

A

Hepatocellular carcinoma

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16
Q

Colorectal carcinomas can arise in a stepwise fashion, explain

A
17
Q

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

A
  • 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
18
Q

What is the common treatment for FAP

A

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

19
Q

are microsatellites scattered throughout the genome

A

yes

20
Q

FAP is caused by a mutation in

A

APC (5q21)

21
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A
22
Q

Explain how the microsatellite instability pathway can result in colonic adenocarcinoma

A
  • 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
23
Q

What is KRAS

A
  • 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
24
Q

About half of melanomas have ____ mutations

A

BRAF

25
Q

What is BRAF

A
  • signal transduction protein downstream of KRAS
  • About half of melanomas have BRAF mutation
26
Q

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

A
  • BRAFV600E (valine to glutamate at amino acid position 600, i.e. a missence mutation normally mutation is T to A)
  • Vemurafenib
27
Q

can mRNA be extracted from cancer and quantified

A
  • Yes
  • it can show the gene expression and the need for more or less aggressive therapy
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30
Q

There are how many molecular building blocks of life

A

68

31
Q

What is systems biolgy

A

quantify systems components and group into networks

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