Neoplasia 4 Sept28 M2

Question 1

main characteristics of normal stem cells

Answer 1

capable of self-renewal

asymmetrical replication

Question 2

two main types of normal stem cells

Answer 2

adult and embryonic

Question 3

charact of embryonic stem cells

Answer 3

present in inner cell mass of blastocyst: unlimited potential

Question 4

charact of adult stem cells

Answer 4

• less undifferentiated. differentiate into cells of particular tissue or ogan
• difficult to find and isolate. quiescent.

Question 5

function of normal embryonic stem cells

Answer 5

give rise to all cells in organism

Question 6

function of normal adult stem cells

Answer 6

homeostasis of cell populations, especially in organs with high turnover

Question 7

2 ways cancer stem cells arise

Answer 7

• from normal stem cells

- from differentiated tissue cells

Question 8

considerations in treating cancer of stem cells (2)

Answer 8

resistant to therapy because

• low rate of replication (can’t target rapidly dividing cells with chemotherapy)
• express factors like multiple drug resistance 1

Question 9

3 types of genes in affected in cancer

Answer 9

oncogene, tumor suppressor gene, DNA repair gene

Question 10

3 main hallmarks of cancer

Answer 10

• evasion of cell death
• unlimited replicative potential
• sustained angiogenesis

Question 11

regulation of normal cell proliferation: steps

Answer 11

growth factor-receptor-transfuction to cytoplasm protein or mt bcl2 proteins.
cyto proteins affect nuclear TFs which lead to advance in cell cycle, proliferation.
bcl2 regulate apoptosis so get either survival or apoptosis

Question 12

how oncogenes disrupt normal cell proliferation cascade

Answer 12

give sustained proliferative signals

Question 13

how tumor suppressor genes disrupt normal cell proliferation cascade

Answer 13

loss of sensitivity to growth inhibitory stimuli. No more restriction to proliferation

Question 14

how defects in DNA repair genes disrupt normal cell proliferation cascade

Answer 14

lead to genomic instability, facilitate mutations in proto-oncogenes and tumor suppressor genes

Question 15

example of proto-oncogene or oncogene

Answer 15

RAS

Question 16

Normal function of RAS

Answer 16

growth factor-EGFR-RAS activated-RAF activated-MEK activated-MAPK activated-cell cycle proliferation

Question 17

Treatment to colonic cancer if RAS working and its limit

Answer 17

Anti-EGFR antibody. If wild RAS, never activated so no cell proliferation
If RAS mutated, constant prolif signals

Question 18

5 things oncogenes can be and examples for each

Answer 18

• Growth factors: PDGF
• Growth factors receptors: HER2-NEU
• Signal transducing proteins (RAS)
• Nuclear TFs (MYC)
• Cyclins and CDKs

Question 19

example of tumour suppressor gene

Answer 19

TP53

Question 20

normal function of TP53

Answer 20

• arrest cell cycle in late G1
• assist in DNA repair
• apoptosis if DNA can’t repair
• angiogenesis inhibition

Question 21

angiogenesis definition

Answer 21

blood vessel neoformation from preexisting vasculature

Question 22

vasculogenesis def

Answer 22

blood vessel formation from endothelial progenitor cells (mesenchyme)

Question 23

arteriogenesis def

Answer 23

growth and remodelling of collateral preexisting arterioles to form large well-muscularized conductance arteries and arterioles to compensate on closed arteries

Question 24

how tumor angiogenesis occurs

Answer 24

disruption of the balance between angiogenic factors (VEGF**) and angiogenic inhibitors

Question 25

stimuli for angiogenesis

Answer 25

ischemia, hypoxia, injury, inflammation, shear stress

Question 26

5 steps of neovascularizition

Answer 26

• BM degraded
• chemotaxis of endothelial cells to angiogenic stimulus
• elongation and alignement of endothelial cells
• endothelial cell proliferation
• BM produced

Question 27

how endothelial cells of tumor vessels are different from normal vessels

Answer 27

more fenestrations, more permeable, A-V shunts, loops, abnormal architecture, 50x rate division, express surface integrins (VEGF-R), secrete growth factors and cytokines (autocrine and paracrine loops)

Question 28

mistake when thinking about tumour vessels

Answer 28

Mistake is to think they have mutations

Question 29

Examples of DNA repair genes that can be defective in neoplasm

Answer 29

MSH2, MLH1, PMS1 and PMS2