PPT 3

Question 1

Aanpassingen in genome accumuleren bij tumor progessie. Aanpassingen:

Answer 1

• verhoging neoplasme
• proto-oncogene activatie + tumor suppressor inactivatie (meer inactivatie TSG)
• loss of heterozygosity (1 / 2 allels)

Question 2

Cancer cells compete for

Answer 2

limited resources

Question 3

Selection favors …

Answer 3

cancer cells with advantegeous traits
- proliferation
- survival

Question 4

Cancer stem cells

Answer 4

CSCs
- A minority of self-renewing tumor cells that are able to ’recreate’ the tumor (even a single CSC!)
- fenotype wordt altijd niet behouden in afstammelingen
- self-renewing, unlimited potential for division

Question 5

Tumors are highly heterogenous

Answer 5

• Mutation rates increase with tumor progression (genome instability)
• Darwinian selection can’t keep up with genetic diversity (proliferation & survival)
• Distinct subclones can coexist within a single tumor
• Epigentic plasticity within a tumor adds another layer of complexity

Question 6

Transformation usually requires

Answer 6

2+ mutant genes
- Truly normal primary cells are resistant to a single-hit transformation

Question 7

Fibroblast are difficult to transform

Answer 7

• muis kan het wel > 2 oncogenen activeren
• mens: cell worden non-proliferative
  > meestel 5-6 verschillende circuits need to be disrupted simultaneously for transformation

Question 8

Peto’s paradox

Answer 8

Within one species, cancer risk and body size are positively correlated. But between species, the incidence of cancer does not appear to correlate with the number of cells in an organism
- groter organisme: more developed tumor suppression mechanisms & bigger en slower dividing cells w/ lower turnover energy

Question 9

Promote tumorigenesis (niet DNA)

Answer 9

Non-mutagenic & toxic agents
- roken
- alcohol
(dying epithial cells stimulates stem cell proliferation)

Question 10

Mitogenic agents promotes tumorigenesis

Answer 10

Steroid hormones promote cell growth
> estrogen & progesterone stimulate proliferation of reproductive tissue
- more menstrual cycles? > higher risk at cancer

Question 11

Anti-inflammation drugs … cancer risk

Answer 11

Reduce
- Aspirin (Non-steriod anti-inflammatory drug, NSAID)
- target: cyclooxygenase-2 (COX-2), responsible for biosynthesis progstaglinden E2 (PGE2), proinflammatory molecule with tumor promoting capabilities

Question 12

Carcinogen

Answer 12

any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer)
Complete carcinomas = initiate and promote tumorigenesis

Question 13

Carcinogenesis

Answer 13

oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells.

Question 14

Mutagen

Answer 14

physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level

Question 15

Carcinogen ≠ mutagen

Answer 15

Mitogenic agents do not always work by damaging DNA