Tumour pathology 4

Question 1

What is cell cycle

Answer 1

Time interval between mitotic division

Question 2

What is the timing for the cell cycle

Answer 2

G1- 8 hours
S- 10hr
G2-5hrs
M-hr

Question 3

What is external factors in the cell cycle

Answer 3

Hormones, growth factors, cytokines, stroma

Question 4

What is intrinsic factors in cell cycle

Answer 4

critical checkpoints - Restriction point (R)

Question 5

prior to restriction point progress what does G1 depends

Answer 5

external stimuli

Question 6

After restriction point what does the progression of the cell cycle become

Answer 6

autonomous - indépendant

Question 7

What are the reasons G1 or G2 arrest the cell cycle

Answer 7

If cell size inadequate - G1 or G2 arrest
If nutrient supply inadequate - G1 arrest
Essential external stimulus lacking - G1 arrest
If DNA damage is detected - G1 or G2 arrest

Question 8

when Mphase arrest the cell cycle

Answer 8

Chromosome mis-alignment - M-phase arrest

Question 9

Where are the checkpoints in the cell cycle

Answer 9

G1 G2 M

Question 10

What are checkpoints?

Answer 10

catalytic subunits are called cyclin-dependent kinases (CDKs) activated by regulatory sub-units called cyclins

Question 11

What is the checkpoint active enzyme complex called

Answer 11

CDK/cyclin complex

Question 12

How do CDK/cyclin complex work as check point mediators

Answer 12

phosphorylation of target proteins resulting in activation/inactivation of that substrate

Question 13

What does the substrate do in the next phase of the cell cycle

Answer 13

Regulates events

Question 14

What happens to cyclins in the cell cycle

Answer 14

accumulate and are destroyed by cell progress

Question 15

How are CDKS expressed

Answer 15

inactive form

Question 16

What two families of CDK inhibitors (CDKis) are important to checkpoints?

Answer 16

INK4A family and CIP/KIP family

Question 17

How do CDK inhibitors work

Answer 17

Bind to CDK complex

Question 18

What do active cyclin D/CDK complexes phosphorylate

Answer 18

pRb

Question 19

What is hypophosphorylated pRbs function

Answer 19

bind to E2F

Question 20

What happens when pRb is phosphorylated?

Answer 20

Becomes inactivated and looses its affinity for E2F, therefore free E2F can activate vital target genes stimulating cell cycle entry

Question 21

What does active pRb act as

Answer 21

a brake in the cell cycle

Question 22

What normal balance does carcinogeneis upset

Answer 22

Proliferation and apoptosis

Question 23

Where can mutations occur to cause a cell to loose control of its proliferation

Answer 23

genes regulating cell division,
apoptosis,
DNA repair

Question 24

What is the environmental agents causing cacinognesuis

Answer 24

Chemicals
Radiation
Oncogenic viruses

Question 25

What is damaged in DNA by various oxidizing and alkylating agents

Answer 25

purine and pyrimidine bases

Question 26

What is DNA adducts

Answer 26

Chemical carcinogens or their active metabolites react with DNA forming covalently bound products

Question 27

What does adduct formation at particular chromosome site cause

Answer 27

cancer

Question 28

High-energy radiation is carcinogenic if received in sufficient doses of what types of radiation

Answer 28

ultraviolet radiation (UV-B present in sunlight) X-rays Gamma radiation

Question 29

What is the primary defect in cancer

Answer 29

Uncontrolled cell proliferation via | cell cycle dysregulation

Question 30

What are the two regulatory pathways frequently disrupted in the cell cycle

Answer 30

The cyclin D-pRb-E2F pathway - G2 check point | p53 pathway - G1 checkpoint

Question 31

What happens if the The cyclin D-pRb-E2F pathway

Answer 31

Absent or inactive pRb releases the cell cycle brake

Question 32

Where are all cancers disregulated due to mutations

Answer 32

G1-S

Question 33

Disregulation at the G1 - S is because of the Mutation in what four potential genes

Answer 33

Rb, CDK4, cyclin D and p16 (multiple tumor suppressor)

Question 34

What is the function of P53

Answer 34

Maintain the integrity of cells by facilitating DNA repair and arresting at G1

Question 35

Where are p53 levels increased

Answer 35

in damaged cells

Question 36

What happens to cells with mutated p53 gene

Answer 36

do not G1 arrest or repair damaged DNA | therefore damaged cells proliferate and form malignant neoplasms

Question 37

What mutations in other genes mimic the effect of pRb loss and drive proliferation

Answer 37

Mutational activation of cyclin D or CDK4 | Mutational inactivation of CDKIs

Question 38

What cancer is cause by the amplification of cyclin dependant kinase

Answer 38

Melanoma, sacroma

Question 39

What is the malignant mutation is caused by the p16(INK4a) that inhibits CDk’s

Answer 39

melanoma

Question 40

What malignant cancer arrises from rB mutation

Answer 40

retinoblastoma

Question 41

How do retrovirus cause cancer

Answer 41

insert onocongene into host causing rapid cell division