10. Neoplasms Flashcards

1
Q

What is carcinogenesis?

A

Causes of cancer.

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2
Q

What are some intrinsic causes of neoplasia?

A

Age, sex, heredity.

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3
Q

What are some extrinsic causes of neoplasia?

A

Environment, lifestyle.

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4
Q

What are the five leading behavioural and dietary risks of cancer?

A

High body mass index, low fruit and vegetable intake, lack of physical activity, tobacco use, and alcohol use.

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5
Q

What proportion of cancer deaths are due to the five leading behavioural and dietary risks?

A

30%.

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6
Q

What are the three main categories of extrinsic carcinogens?

A

Chemicals, radiation, and infections.

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7
Q

What did malignant neoplasms caused by 2-napthylamine (industrial carcinogen in dye) show?

A

There is a long delay between carcinogen exposure and malignant neoplasm onset. The risk of cancer depends on the total carcinogen dosage. There is sometimes organ specificity for particular carcinogens

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8
Q

What does the Ames test show?

A

That initiators are mutagens while promoters cause prolonged proliferation in target tissues.

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9
Q

What is done in the Ames test?

A

A strain of bacteria that requires histidine to grow is split into two batches: one has a possible mutagen added then both are placed in media with minimal histidine. After incubation, only the batch with possible mutagen added has a high number of revertants - this suggests the mutagen causes mutations.

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10
Q

What is progression?

A

The process through which a mutant monoclonal collection of cells eventually becomes fully malignant.

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11
Q

In what way do neoplasmic cells have a ‘head start’ in germline mutations?

A

The normal steps of initiation and some promotion can be skipped.

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12
Q

What are the classifications of mutagenic chemical carcinogens?

A

Polycyclic aromatic hydrocarbons, aromatic amines, N-nitroso compounds, alkylating agents, and diverse natural products.

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13
Q

How are some pro-carcinogens converted to carcinogens?

A

By the cytochrome P450 enzymes in the liver.

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14
Q

What are complete carcinogens?

A

Carcinogens that act as both initiators and promoters.

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15
Q

What is radiation?

A

Any type of energy travelling through space.

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16
Q

What is the effect of ionising radiation on atoms?

A

Strips electrons from atoms.

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17
Q

What are ionising energy types?

A

Alpha particles, beta particles, gamma rays, and X rays.

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18
Q

What are electromagnetic energy types?

A

Gamme rays, X rays, and UV rays.

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19
Q

What are nuclear energy types?

A

Alpha particles, beta particles, and gamma rays.

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20
Q

What are the two types of damage to DNA from radiation?

A

Direct damage and indirect damage by generating free radicals.

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21
Q

How does radiation damage DNA directly?

A

Altering bases, single/double strand DNA breaks.

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22
Q

How does radiation damage DNA indirectly?

A

Free radicals.

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23
Q

What are some sources of exposure to radiation?

A

UV - sunlight, ionising - radon, medical tests, or frequent flying.

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24
Q

How can infections damage DNA?

A

Directly or indirectly.

25
Q

How can infection directly damage DNA?

A

Affect genes that control cell growth.

26
Q

How can infection indirectly damage DNA?

A

Causing chronic tissue injury, the resulting regeneration acts as a promoter for any pre-existing mutations or causes new mutations from DNA replications errors.

27
Q

Wat type of carcinogen is HPV (human papilloma virus)?

A

Direct carcinogen.

28
Q

How is HPV a direct carcinogen?

A

It expresses the E6 and E7 proteins that inhibit p53 and pRB protein function respectively, both of which are important in cell proliferation.

29
Q

What are the roles of p53 and pRB?

A

To initiate cell apoptosis, when suppressed this means cells unusually survive.

30
Q

What type of carcinogens are Hepatitis B and C viruses?

A

Indirect carcinogens.

31
Q

How do Hepatitis B and C viruses act as carcinogens?

A

They cause chronic liver cell injury and regeneration. This leads to increased of mutations.

32
Q

How can helicobactor pylori increase the risk for gastric, cholangio- and bladder carcinomas?

A

It causes chronic gastric inflammation and parastitic flues cause inflammation in bile ducts and bladder mucosa, so there is increased risk.

33
Q

How does human immunodeficiency virus (HIV) indirectly act as a carcinogen?

A

It lowers immunity and allows other potentially carcinogenic infections to occur.

34
Q

What pattern of inheritance does retinoblastoma have?

A

Dominant pattern of inheritance.

35
Q

How was the dominant pattern of inheritance for retinoblastoma discovered?

A

Retinoblastoma is a childhood disease. A child had theirs removed and went on to have children, all these children then developed retinoblastomas.

36
Q

What is the two hit hypothesis in retinoblastoma? Explain for familial and sporadic retinoblastoma.

A

For familial cancers, the first hit was delivered through the germline and affected all cells in the body. The second hit is a somatic mutation in one of the 10 million + retinal cells.
For sporadic retinoblastoma, both hits have to be mutations in the somatic cells.

37
Q

What genes inhibit neoplastic growth?

A

Tumour suppressor genes.

38
Q

How can tumour suppressor genes stop working?

A

If both alleles are mutated, hence the two hit theory.

39
Q

What genes enhance neoplastic growth?

A

Oncogenes, which are abnormally activated versions of the normal proto-oncogenes.

40
Q

How is neoplastic growth favoured?

A

If both tumour suppressor gene alleles have been deactivated or one proto-oncogene has been abnormally activated into oncogenes.

41
Q

What is the RAS proto-oncogene?

A

It encodes a small G protein that relays signals into the cell that eventually push the cell past the cell cycle restriction point by phosphorylating Rb.

42
Q

How does the RB gene restrain cell proliferation?

A

By inhibiting passage through the restriction point.

43
Q

What does inactivation of both RB alleles allow?

A

Unrestrained passage through the restriction point.

44
Q

How can the restriction point of growth control by deregulated?

A

By the combination of an activated oncogene and an inactivated tumour suppressor gene.

45
Q

What do the types of proto-oncogenes encode?

A

Growth factors, growth factor receptor, plasma membrane signal transducers, intracellular kinases, transcription factors, cell cycle regulators, or apoptosis regulators.

46
Q

What is xeroderma pigmentosum due to?

A

Mutations in one of the seven DNA repair genes that affects DNA nucleotide excision repair.

47
Q

What is hereditary non-polyposis colon cancer syndrome associated with?

A

Colon carcinoma and germline mutations that affect one of several DNA mismatch repair genes.

48
Q

What is familial breast carcinoma associated with?

A

Mutations in BRCA1 or BRCA2 genes that normally repair double strand DNA breaks.

49
Q

What is genetic instability?

A

Alterations in genes that account for the accelerated mutation rate found in malignant neoplasms.

50
Q

What are caretaker genes?

A

Genes that maintain genetic stability, class of tumour suppressor genes.

51
Q

What is an inherited syndrome that affects nucleotide excision repair and by what effect on the genome?

A

Xeroderma pigmentosa, by nucleotide instability.

52
Q

What is an inherited syndrome that affects mismatch repair and by what effect on the genome?

A

HNPCC, by microsatellite instability.

53
Q

What is an inherited syndrome that affects double strand break repair and by what effect on the genome?

A

Breast/ovarian cancer, by chromosomal instability.

54
Q

What is progression?

A

The steady accumulation of multiple mutations.

55
Q

How does colon carcinoma develop? (Include the genes involved).

A

Starts as normal epithelium and then APC gene is mutated. This leads to early adenoma/dysplastic crypt. KRAS gene mutation leads to intermediate adenoma. Smad2/4 mutation causes late adenoma, which develops to carcinoma after p53 mutation. Finally, other genetic mutations lead to metastases.

56
Q

What are the three stages of cancer evolution?

A

Initiation, promotion, and progression.

57
Q

What are the six hallmarks of cancer that fully evolved malignant neoplasms exhibit?

A

Self-sufficiency in growth signals, resistance to growth stop signals, no limit on the number of times a cell can divide (cell immortalisation), sustained ability to induce new blood vessels (angiogenesis), resistance to apoptosis and the ability to invade and produce metastases.

58
Q

Which hallmark of cancer is exclusive to malignant neoplasms, rather than relevant to benign and malignant neoplasms?

A

Hallmark 6: ability to invade and produce metastases.

59
Q

What is a simplified cancer pathogenesis?

A

Somatic cells are exposed to environmental carcinogens that are either initiators or promoters culminating in a monoclonal population of mutant cells. In 5% of cancer inherited mutations in the germ line can be present. Some of these clones harbour mutations affecting a proto-oncogene or tumour suppressor gene, whose protein transcripts play crucial roles in cell signalling pathways affecting hallmark changes. In progression, cells acquire further activated oncogenes or inactivated tumour suppressor genes, some include genetic instability. This eventually results in a population of cells that have acquired a set of mutations that produce all of the hallmarks of cancer.