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Pathology > Neoplasia V > Flashcards

Neoplasia V Flashcards

1
Q

What is the function of the APC gene, and what are the cancers associated with it?

A

Function = prevents nuclear transcription by binding to Beta-catenin

CA= familial polyposis coli

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2
Q

What is the function of the BRCA-1/2 genes, and what are the cancers associated with it?

A

Function = Regulates DNA repair

CA= breast/ovarian CA

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3
Q

What is the function of the Rb gene, and what are the two cancers associated with it?

A

Inhibits G1 to S phase

Retinoblastoma
Osteogenic sarcoma

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4
Q

What is the function of the TGF-beta gene, and what are the cancers associated with it?

A

Inhibits G1 to S phase

Pancreatic and colorectal gene

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5
Q

What is the function of the WT-1/WT-2 gene, and what are the cancers associated with it?

A

Regulates nuclear transcription

Wilms tumor
Beck-wiedemann syndrome

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6
Q

What is the WNT signalling pathway?

A

Controls cell fate, adhesion, and polariry during embryonic development

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7
Q

the APC gene and beta-catenin gene are involved in what pathway?

A

WNT

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8
Q

What is the function of APC protein in the WNT pathway?

A

Down regulates Beta-catenin to prevent its accumulation

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9
Q

What happens in the WNT pathway when WNT binds?

A

Inactivation of the APC, leading to increase beta-catenin levels

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10
Q

What does beta-catenin bind to?

A

TCF factor in the DNA

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11
Q

What type of CA does beta-catenin upregulation lead to?

A

FAP

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12
Q

What are the three CAs that are associated with the Rb gene?

A

Retinoblastoma
Osteosarcoma
Soft tissue sarcoma

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13
Q

What percent of Rb dysfunctions are familial? Sporadic?

A

60% sporadic

40% familial

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14
Q

What is Knudson’s two hit hypothesis?

A

Both alleles of Rb must be inactivated/mutated for CA to develop

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15
Q

Where does the “second hit” occur in familial Retinoblastoma?

A

Retinal cells (first in somatic cells)

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16
Q

True or false: Heterozygous Rb genes form CA

A

False–need homozygous

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17
Q

What is the function of the p53 gene? Associated CAs?

A

function = inhibits G1 to S phase, repairs DNA, activates BAX

Lung, colon, breast CA

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18
Q

What is Li-Fraumeni syndrome?

A

CA caused by inactivation of p53

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19
Q

What is the specific pro-apoptotic protein that p53 activates?

A

BAX

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20
Q

p53 arrests the cell cycle at which phase? How?

A

G1/S phase

Acts via p21 (cyclin CDK4 inhibition)

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21
Q

What is the function of p21?

A

G1 arrest (cyclin CDK4 inhibition)

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22
Q

What is the function of GADD45 that p53 upregulates?

A

DNA repair mechanism

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23
Q

What happens to p53 in tumors?

A

Inactivated (mutated)

24
Q

What is the function of HPV E6 protein?

A

inhibits p53

25
Q

What is the function of HPV E7 protein?

A

inhibit p21 and Rb-E2F

26
Q

What is the function of VHL? What chromosome is it one?

A

Anti tumor gene on chr 3.

Part of the ubiquitin ligase complex that regulates the HIF-1alpha transcription

27
Q

What are the CAs associated with VHL mutations?

A

Hereditary renal cells carcinomas

Pheochromocytomas
Hemangioblastomas of CNS

28
Q

What is Warburg effect?

A

Even in presence of ample O2, CA cells demonstrate a distinct form of metabolism characterized by high levels of glucose uptake and increased concentration of glucose to lactose via the glycolytic pathway

29
Q

What is the basis for PET scans?

A

Tumors like Glucose (Warburg effect) Thus can label glucose

30
Q

True or false: Carcinogenesis occurs in a single step

A

False–multistep process and accumulation of mutations

31
Q

How long does telomerase last in normal cells? Then what happens (normally)?

A

60-70 doublings, then p53 activated

32
Q

What is the function of telomerase in CA development?

A

Maintains telomere length

33
Q

DNA methylation upregulates or downregulate gene expression? How?

A

Downregulates– condenses chromosome

34
Q

What are miRNAs?

A

family of 19-24 nucleotides that regulate mRNA function at the posttranscriptional level

35
Q

What percent of cancer are the result of chemical carcinogens?

A

80-90%

36
Q

What are chemical carcinogens?

A

highly reactive electrophiles that remove electron from DNA

37
Q

What does it mean when a carcinogen has a “direct action” effect?

A

Act without modification

38
Q

What does it mean when a carcinogen has an “indirect action” effect?

A

Require metabolic activation

39
Q

What is the relationship between promoters and initiators?

A

Promoter given after initiator, and in a short time frame, is associated with CA development

40
Q

What are initiators

A

Chemical that initiate carcinogenesis, and produce cell alteration

Not sufficient for tumor formation

41
Q

What are promoters?

A

Induces tumors in initiated cells

Non-tumorigenic by themselves

42
Q

What are polycyclic aromatic hydrocarbons?

A

Products of combustion

Associated with lung and bladder CAs

43
Q

What type of CAs are associated with aromatic amines and Azo dyes? MOA?

A

liver CA

action of p450 cytochrome oxygenase system

44
Q

What is beta-naphthylamine? What CA is it associated with?

A

Material used in rubber industry

Bladder CA

45
Q

What is Aflatoxin B1?

A

Carcinogenic mycotoxin produced by aspergillus flavus in corn/peanuts

46
Q

What is the effect of Aflatoxin B1?

A

Hepatocellular carcinoma d/t p53 mutation

47
Q

What is the MOA of Nitrosamines and amines

A

Formed in Gut of humans, associated with gastric carcinoma

48
Q

Asbestos is associated with what CAs?

A

Mesothelioma (but lung CA more often)

49
Q

Chromium, nickel associated with what CAs?

A

lung CA

50
Q

Arsenic is associated with what type of CA?

A

Skin CA

51
Q

What is the effect of estrogen in carcinogenesis? What CA is this associated with?

A

Promoter of chemical carcinogenesis

Liver CA

52
Q

What is the effect of diethyl-stilbesterol?

A

Promoter of Postmenopausal endometrial CA

53
Q

What is the MOA of high fat diet?

A

Increased bile acid production

Colon CAs

54
Q

What are the molecules associated in the WNT pathway, and how do they lead to CA?

A

WNT receptor inhibits APC from inhibiting Beta catenin.

If there is no APC d/t mutation, then FAP

55
Q

p53 acts through what other p# molecule to inhibit CDK4/cyclin

A

P21

56
Q

What is the MOA of direct carcinogens? Indirect?

A 
Direct = React with DNA
Indirect = usually metabolized by p450

Pathology (32 decks)

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