HC3 - Multi-step tumorigenesis

Question 1

senescence

Answer 1

• non-growing but viable state
• provoked by a variety of physiological stresses

Question 2

crisis

Answer 2

• apoptotic death of cells
• provoked by erosion of telomeres

Question 3

pre-malignant cells escape crisis

Answer 3

activate expression of hTERT

Question 4

hTERT

Answer 4

telomerase enzyme that exends telomeres in hexanucleotide increments

Question 5

immortal cells

Answer 5

• stabilize telomeres with telomerase or ALT mechanism
• prerequisite to the development of all human cancers

Question 6

end-to-end chromosomal fusion

Answer 6

• repeated cycle of breakage-fusion-bridge (BFB) cycle
• aneuploidy

Question 7

development cancers

Answer 7

over years/decades

Question 8

curing all cancer

Answer 8

raises life expectancy with 3-5 years > due to late onset

Question 9

risk of death

Answer 9

increases as 4-7th power of elapsed life

Question 10

different tumor progressions cooexist

Answer 10

use of progression schemes for determination

Question 11

surgical removal of early-stage lesions

Answer 11

reduces risk of disease

Question 12

increasing neoplastic phenotypes

Answer 12

correlates with corresponding increase in the number of altered loci

Question 13

genomic alterations

Answer 13

• proto-oncogenic activation an tumor suppressor gene inactivation
• accumulate with tumor progression

Question 14

loss of heterozygosity (LOH)

Answer 14

can expose a faulty allele if it was masked/dominated

Question 15

colon carcinomas

Answer 15

~80% inactive APC gene

Question 16

multiple genetic routes

Answer 16

can lead to a similar outcome

Question 17

tumor progression

Answer 17

a series of clonal expensions

Question 18

survival of the fittest in tumors

Answer 18

cancer cells compete for limited resources

Question 19

selection in tumors

Answer 19

favors cells endowed with ability to proliferate and survive in tisse

Question 20

highly heterogenous tumors

Answer 20

• genomic instability > mutation rate increases
• Darwinian selection cannot keep up with genetic diversification
• specific subclones > may support each other
• more complexity > epigenetic plasticity

Question 21

Peto’s paradox (Richard Peto)

Answer 21

• within one species > cancer risk and body size = positively correlated
• between species > no correlation between incidence and number of cells

Question 22

larger organisms (Peto’s paradox)

Answer 22

• may have more developed tumor suppression mechanisms
• bigger and slower dividing cells
• lower energy turnover

Question 23

truely normal primary cells

Answer 23

resistant to single hit transformation

Question 24

difficulty with transformation of human fibroblasts

Answer 24

5-6 different circuits need to be disrupted simultaneously

Question 25

non-mutagenic/toxic agents

Answer 25

promote tumorigenesis

Question 26

tabacco smoke

Answer 26

source of genotoxic chemicals

Question 27

alchohol

Answer 27

very toxic to epithelial cells of mouth and throat

Question 28

mitogenic agents

Answer 28

promote cell proliferation

Question 29

steroid hormones

Answer 29

estrogen and progesteron > stimulate proliferation of cells in reproductive tissues

Question 30

more menstruation cycles

Answer 30

leads to higher risk in breast cancer, 1 year absence = 20% decrease in risk

Question 31

chronic inflammation

Answer 31

promotes tumorigenesis

Question 32

anti-inflammatory drugs

Answer 32

reduce cancer risk

Question 33

non-steroid anti-inflammatory drug (NSAID)

Answer 33

asparin

Question 34

common targets NSAIDs

Answer 34

• cyclooxygenase-2 > biosynthesis of prostagladin E2 (PGE2)

Question 35

prostagladin E2 (PGE2)

Answer 35

pro-inflammatory molecule with tumor-promoting capabilities

Question 36

carcinogenic

Answer 36

not equal to mutagenic

Question 37

complete carcinogens

Answer 37

genotoxic and mitogenic, can initiate and promote tumorigenesis