neoplasia 2

Question 1

carcinogenesis - define

Answer 1

initiation of cancer formation

Question 2

pinciples of carcinogensis

Answer 2

non-lethal damage
tumor formed by clonal expansion of single precursor that incurred damage
4 classes of regulatory genes must be mutated
carcinogenesis is mutli-step

Question 3

non-lethal damage is key

Answer 3

tumor cell acquires mutations. if lethal = wont replicate. cell survival in altered form.

Question 4

what causes mutations?

Answer 4

enviornmental agents - teratogen, virus, bacteria.
back luck - spontaneous mutation
inherited in germ line.

Question 5

tumor formed by clonal expansion of single precursor cell that has incurred damage

Answer 5

monoclonal.

one cell, multiple mutations.all cells within neoplasm will have same mutations that caused neoplasm to form

Question 6

4 classes of normal genes

Answer 6

oncogenes
tumor suppressor genes
apoptotic gene
DNA repair genes
* first cell to mutate all 4 = neoplasia

Question 7

carcinogenesis is mutli-step

Answer 7

cancers result from accumulation of mutliple mutations.

tumor pregression. - cells can acquire own mutations different from onw another.

Question 8

6 characteristic btw normal cell vs malignant

1. response to growth signal
2. respons to growth inhibitory signal
3. response to apoptotic singal
4. ablility to repair DNA
5. angiogenesis
6. invade and spread

Answer 8

N   M 
controlled .. self-sufficient
y  N
Y  N
y  n
limited .. induced
n  y

Question 9

failure of DNA repair

Answer 9

inherited mutations in genes affecting DNA repair, cell growth or apoptosis.

Question 10

1. oncogene function

what signalling pathway??

Answer 10

gene promotes autonomous growth of cancer cells.
cant be inherited - incompatible with life.
RAS - RAF pathway. too many growth factors = replication without control or no growth factor needed to activate.

Question 11

1. proto-oncogene & oncoprotein

Answer 11

proto-onco = un-mutated cellular counterpart. drives normal cell thru cell cylce
oncoprotein: product of oncogene = lack regulatory elements of proto-oncogene.

Question 12

1. cell cycle
   - two proteins complex
   important protein at G1/G2

Answer 12

cyclin d1 and cdk 4 complex to drive cell protein to activations.
RB protein - when hyperphosphorylated = active.

Question 13

2. growth inhibitory signals

Answer 13

tumor suppressor genes = stop cel proliferation

two-hit hypothesis: need two mutations, loss of heterozygosity ( or haploinsuffiency) to lack inhibitory process.

Question 14

2. RB tumor suppressor gene

Answer 14

doing its job = hypophosphorylated - quiescent cell. inhibit DNA transcription.
hyperphosphorylated = activates transcription.
* normally inhibits transcription of genes for G1/S checkpoint.
* mutates = cell cycle not under this control

Question 15

2. retinoblastoma

why does RB protein mutation only produce retinoblastoma?

Answer 15

-familial= heterozygous for mutated allele, only need one mutation for LOH.
two hits = lethal. cant support life.
- Rb protein only regulatory protein in eye. other body parts have more. easily susceptible to retinoblastoma

Question 16

3. apoptosis

tumors and apoptosis. inactivation of?

Answer 16

programmed cell death.

tumors resistant. bc inactivate p53

Question 17

3. action of p53 in normal cells

Answer 17

temporary, permanent cell cycle arrest activates and signals for apoptosis, when cell in stressed. can revert back to normal state if stress is repaired.
Li-Fraumeni syndrome= mutation of p53. incompatble with life.

Question 18

4. DNA repair

Answer 18

usually enzymes repair damaged DNA. sometimes DNA repair genes damaged/mutated - allow mutations in other genes, not oncogenic on its own.
- germline mutations in DNA repair genes = high risk of malignancy. when born with one mutated gene easier to lose heterozygosity.
HNPCC, BRCA

Question 19

• important characteristic for malignant cell * replicative potential

Answer 19

limitless replicative potential via telomerase.
normal cells, telomerase shorten. mutant p53 doesnt stop cell. 4 short chromosomes add together = dicentric chromosomes. telomerase can act on them and they replicate.

Question 20

senescence

mitotic catastrophe

Answer 20

cell cyle arrest due to shortened telomeres
mitotic catastrophe: 4 short chromosomes come together. usually massive cell death. mutant p53 allows telomerase to continue functioning

Question 21

5. angiogenesis

Answer 21

tumors cant grow without blood supply.

angiogenesis = growth of new vessels from existing capillaries

Question 22

6. invasion and metastasis

Answer 22

malignant cells invade extracellular matric. vascular dissemination. extravasation and metastatic growth. metastatic growth thru basement membrane.

Question 23

carcinogenic agents

Answer 23

chemical, microbial, radiation

Question 24

chemical carcinogen - steps

Answer 24

initiation: exposure of cells to sufficient dose to cause permanent and irreversible alteration
promoter: induce tumor in initiated cell. - push to malignant
direct-acting: no metabolic conversion to be carcinogenic
indirect-acting: require metabolic conversion to be carcinogenic (smoking)

Question 25

microbial carcinogenesis

Answer 25

virus can cause cancer.

bacteria can mutate cells and cause cancer

Question 26

radiation - 3 types

Answer 26

sunshine
iatrogenic (medical exposure)
ionizing (electromagnetic)

Question 27

host defense against tumors

• immune surveillance
• -ttumor antigens
• • antitumor effector mechanisms
• • immunodeficient patients

Answer 27

immune surveillance = body on look out for development of malignancy.

• tumor products elicit immune response
• antitumor effector mechanisms (cell mediated immunity, Ab produced but not protective.
• immunodeficient patients: some malignancies more common in these patients

Question 28

late recurrence

Answer 28

unclear which tumors have late recurrence and why
tumor dormancy = proposed theory - prolonged survival of micrometasteses without progression. remain dormant until metastases are habitable.