Cell Cycle & Growth Flashcards

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1
Q

What is the cyclin/cdk complext for early G1/S transition?

A

cyclin D

cdk 4/6

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2
Q

What is the cyclin/cdk complext for late G1/S transition?

A

cyclin E

cdk 2

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3
Q

What is the cyclin/cdk complext for S progression?

A

cyclin A

cdk 2

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4
Q

What is the cyclin/cdk complext for G2/M transition?

A

cyclin B

cdk 1

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5
Q

Which cell cycle checkpoint is frequently inactivated in tumors?

A

early G1/S (cyclin D, cdk 4/6)

p21 and p15/p16 inhibit the interaction

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6
Q

What is the function of Cyclin D/cdk4/6?

A

it phosphorylates and activates the Rb gene, which releases E2F
E2F then facilitates transcription of cyclins E and A and genes involved in DNA synthesis

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7
Q

What is the function of E/2 and A/2?

A

they further phosphorylate Rb, driving the progression into S

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8
Q

What blocks the progression of G1/S?

A

p53 induces p21 in response to DNA damage –> prevents interaction of Cyclin D and cdk4/6

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9
Q

If p53 is inactivated in a tumor, what happens? What about Rb?

A

No p53 = no G1/S stop
No Rb = constitutive E2F activation = pushes S phase.

Note E6 and E7 facilitate this in HPV

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10
Q

What is the function of Cyclin B/cdk1?

A

It drives progression through G2/M by phosphorylating Histone H1 –> chromosome condensation

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11
Q

What is the mitotic index?

A

MI = % of cells in mitosis (as measured by light micrsocopy, which can ‘see’ condensed chromatin)

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12
Q

What is the labeling index?

A

tritiated thymidine labels cells in S phase

LI =% of cells in S phase

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13
Q

How much of the cell cycle does S phase take up?

A

Approx 1/3

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14
Q

What is BrdU labeling for?

A

Can identify cells in the S-phase by flow cytometry

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15
Q

Approximately how long is S phase?

A

6-8 h

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16
Q

How long is M phase?

A

1 h

17
Q

How long is G2?

A

3-4 h

18
Q

How long is G1?

A

variable!

19
Q

What is the “growth fraction”, what is it for various tumors?

A

The percentage of cells in a tumor that are actively cycling

1) Lymphoma = 90%
2) Squam = 40%
3) Adeno = 5%

20
Q

What is the “cell loss factor”, what is it in most tumors?

A

the percentage of newly produced cells that die. Approx 75% in most tumors

Note: low CLF indicates cells may be resistant to death/therapy

21
Q

What is Tpot? Tvol?

A

Tpot is the potential volume doubling time, not taking into account cell loss
Tvol is the observed volume doubling time

Tpot = Tvol *(1-CLF)
Tpot = Tc/GF
22
Q

What is diameter doubling time?

A

Tvol * 3

23
Q

What is the average for tumors:

1) Tc
2) Tpot
3) Tvol
4) Tdiam

A

1) 2 days
2) 5 days
3) Assuming 75% cell loss, = 20 days
4) 60 days

24
Q

What is the theory behind accelerated repopulation?

A

prolonged cytotoxic treatment stimulates tumor cells to rapidly divide. This has been seen in HNSCC and cervical cancers

25
Q

What is “kickoff time” and “Dprolif”?

A

kickoff time is the delay between treatment start and accelerated repopulation. Once kickoff time is reached, additional dose must be given to counteract this (Dprolif)

26
Q

What is hydroxyurea used for?

A

HU selectively kills cells in the S-phase (inactivates ribonucleotide reductase), thus accumulates cells at G1/S checkpoint

27
Q

At what phase of the cell cycle are cells most sensitive to RT?

A

In G2/M transition, as there is not enough time to repair the DNA before dividing –> mitotic catastrophe

28
Q

When are cells least sensitive to RT?

A

In S phase – extensive templates for HRR

29
Q

What does Dq look like in the various cell cycle phases?

A

In G2/M, there is very little repair going on, so Dq (shoulder) is small
In S there is very good repair going on, so Dq (shoulder) is large

30
Q

At what phase of the cell cycle is OER maximally influential?

A

S phase since so much DNA repair going on

31
Q

What is the influence of LET on cell cycle sensitivity?

A

Minimal

32
Q

How does cell cycle impact dose rate sensitivity?

A

In ultra-low dose rate brachy, cells are able to reassort in the cell cycle and accumulate in the G2 phase, where they are maximally sensitive. = inverse dose rate effect