Tumour growth kinetics

Question 1

How can growth kinetics paramters be meausured in a tumour?

Answer 1

Cell cycle-TC
Growth fraction and potential doubling time-Tpot
cell loss factors-0/
Doubling time-td

Question 2

Why doesn’t 30 doubling of tumour cells lead to 1 gram of tumour if it’s exponential growth?

Answer 2

Because not alll cells are dividing at all times and different cell types have different TC values

Question 3

What does Tpot measure? How is it measured?

Answer 3

The shortest number of time a cell population taking into account proliferative and non proliferative can double it’s amount .
TC/growth fraction

Question 4

T/F

Cells have differing cell loss factors, epithelial with a factor of 1

Answer 4

True

Question 5

What is TD? How is it calculated?

Answer 5

It is the shortest time of doubling taking into account growth fraction and cell loss factor. Tpot/(1-/0)

Question 6

What techniques are used to measure cell kinetics and how is it done?

Answer 6

It is stained and labelleling through
mitotic counting-stain nucleus and through immunocytochemistry count number of dividing cells based off morphology
tritration thymidine-add radioactive precursor DNA- thymidine which is incorporated in Sphase cells only analyzed using autoradiography
DNA labelling-

Question 7

How do you measure growth fraction?

Answer 7

Ki-67-binds to nucleus of cells in G1,S,G2, directly measures proliferative cells.
BrDU thymidine analogue, incorporated into newly synthesized DNA analyzed by immunocystochemistry or flow cytometry after adding antibody against BRDU

Question 8

How is nuclei received and analyzed?

Answer 8

Stained with formalin fixed paraffin embedded block
Cut
dewax with xylene and rehydrate with alcohol
Digest with pepsinHCL
Stain it with propidium iodine
Then measured with flow cytometry

Question 9

How can we measure Tpot directly with BRDU?

Answer 9

By taking the time it takes to syntheisze DNA and dividing by the number of cell dividing at time 0(labelling index)

Question 10

What is the volume doubling time taking everything into account?

Answer 10

66 days

Question 11

What are ways to directly measure doubling time?

Answer 11

x-ray/CT or MRI

Luminescence assay

Question 12

What is the gomperztian growth?

Answer 12

Takes into account cell loss factor, tumour growth is exponential initially and then plateaus over time

Question 13

T/F

There is a direct way to measure cell loss factor

Answer 13

false

Question 14

What are the applications of growth factor kinetics?

Answer 14

prognostics

chemotherapy and radiotherapy effects

Question 15

Example of how kinetic growth can be used in prognostic markers in cancer

Answer 15

KI67 can be used as prognostic for NSLC or breast cancer

Question 16

What is the problem with using growth kinetics as a prognostic marker for cancer?

Answer 16

No all cancer growth is directly proportional to proliferation rates, other factors involved
Inconsistencies in measuring techniques
choice of treatment and dosing schedule will effect proliferation rates

Question 17

What is used as a endpoint in chemotherapy trials? How about in human clinical trial?

Answer 17

Tumour doubling time

overall survival or disease free survival

Question 18

What type of proliferative cells are more sensitive to conventional radiotherapy? Which ones are more sensitive to CHART? Why might that be?

Answer 18

Slower dividing cells.
Faster dividing cells
Because it CHART might not allow cells to repopulate