Tumour pathology 4 Flashcards

1
Q

What is cell cycle

A

Time interval between mitotic division

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2
Q

What is the timing for the cell cycle

A

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

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3
Q

What is external factors in the cell cycle

A

Hormones, growth factors, cytokines, stroma

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4
Q

What is intrinsic factors in cell cycle

A

critical checkpoints - Restriction point (R)

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5
Q

prior to restriction point progress what does G1 depends

A

external stimuli

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6
Q

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

A

autonomous - indépendant

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7
Q

What are the reasons G1 or G2 arrest the cell cycle

A

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

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8
Q

when Mphase arrest the cell cycle

A

Chromosome mis-alignment - M-phase arrest

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9
Q

Where are the checkpoints in the cell cycle

A

G1 G2 M

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10
Q

What are checkpoints?

A

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

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11
Q

What is the checkpoint active enzyme complex called

A

CDK/cyclin complex

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12
Q

How do CDK/cyclin complex work as check point mediators

A

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

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13
Q

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

A

Regulates events

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14
Q

What happens to cyclins in the cell cycle

A

accumulate and are destroyed by cell progress

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15
Q

How are CDKS expressed

A

inactive form

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16
Q

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

A

INK4A family and CIP/KIP family

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17
Q

How do CDK inhibitors work

A

Bind to CDK complex

18
Q

What do active cyclin D/CDK complexes phosphorylate

A

pRb

19
Q

What is hypophosphorylated pRbs function

A

bind to E2F

20
Q

What happens when pRb is phosphorylated?

A

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

21
Q

What does active pRb act as

A

a brake in the cell cycle

22
Q

What normal balance does carcinogeneis upset

A

Proliferation and apoptosis

23
Q

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

A

genes regulating cell division,
apoptosis,
DNA repair

24
Q

What is the environmental agents causing cacinognesuis

A

Chemicals
Radiation
Oncogenic viruses

25
Q

What is damaged in DNA by various oxidizing and alkylating agents

A

purine and pyrimidine bases

26
Q

What is DNA adducts

A

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

27
Q

What does adduct formation at particular chromosome site cause

A

cancer

28
Q

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

A

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

29
Q

What is the primary defect in cancer

A

Uncontrolled cell proliferation via

cell cycle dysregulation

30
Q

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

A

The cyclin D-pRb-E2F pathway - G2 check point

p53 pathway - G1 checkpoint

31
Q

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

A

Absent or inactive pRb releases the cell cycle brake

32
Q

Where are all cancers disregulated due to mutations

A

G1-S

33
Q

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

A

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

34
Q

What is the function of P53

A

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

35
Q

Where are p53 levels increased

A

in damaged cells

36
Q

What happens to cells with mutated p53 gene

A

do not G1 arrest or repair damaged DNA

therefore damaged cells proliferate and form malignant neoplasms

37
Q

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

A

Mutational activation of cyclin D or CDK4

Mutational inactivation of CDKIs

38
Q

What cancer is cause by the amplification of cyclin dependant kinase

A

Melanoma, sacroma

39
Q

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

A

melanoma

40
Q

What malignant cancer arrises from rB mutation

A

retinoblastoma

41
Q

How do retrovirus cause cancer

A

insert onocongene into host causing rapid cell division