CE L5 Angiogenisis - angio continued

Question 1

Angiogenic process:

Answer 1

1. Surrounding cells release angiogentic factors which bind to nearby epithelial cells
2. Endothelial cells activated and produce enzymes which digest the basement membrane
3. Endothelial cells proliferate and migrate out of vessel
4. Adhesion molecules and MMPs aid formation of new blood vessel
5. Vessel is stabilised by smooth muscle and pericytes

Question 2

What cells take part in angio

Answer 2

epithilial cells

Question 3

what 2 things aid formation of new blood vessel

Answer 3

Adhesion molecules and MMPs

Question 4

What stabilises the new blood vessel

Answer 4

smooth muscle

Question 5

direction of new blood vessel is

Answer 5

towards the source of the stimulus (VEGF producing tumour)

Question 6

Why are new blood vessels required in cancer

Answer 6

to bring oxygen and nutrients to the centre

enables growth, invasion and metastasis

Question 7

What does VEGF stand for

how many forms are there

Answer 7

vascular endothelial factor

5 - VEGF-A is best characterised

Question 8

What triggers VEGF

Answer 8

oncogenes and hypoxia mediated stabilisation if TF - drives VEGF transcription

Question 9

4 current approaches to VEGF targeting

Answer 9

Antisense RNA

Question 10

2 other signals that antisense RNA could target to stop angiogenisis

Answer 10

bFGF

PDGF

Question 11

4 current approaches to VEGF targeting

Answer 11

Antisense RNA

Soluble receptors/mab - Avastin

Enzyme inhibitors

Activation of tumour supressors (p53)

Question 12

2 other signals that antisense RNA could target to stop angiogenisis

Answer 12

bFGF

PDGF

Question 13

Why does activation of tumour supressors help target angiogenisis

Answer 13

p53 unpregulates antiangiogeic factors (e.g. thrombospondin, downregulations of bFGF)

Question 14

e.g. of enzyme inhibitors targeting angio

Answer 14

VEGFR inhibitors:
sunitinib
sorafenib

Question 15

What is Avasin

Answer 15

humanised mab. anti VEGFA

used to treat breast/colon/renal cancer in combo

Question 16

Avastin is also called

Answer 16

Bevacizumab

Question 17

How does avastin work

Answer 17

mops up he VEGF-A (the ligand that stimulates angiogenisis).

Question 18

Why must avastin be used early

Answer 18

doesnt affect already formed blood vessels

Question 19

Disadvantage of avastin

Answer 19

if you get damage to another part of the body you cant have angiogenisis

Question 20

Disadvantage of avastin and other antiangiogenisis therapies

Answer 20

if you get damage to another part of the body you cant have angiogenisis

Question 21

Advantages of antiangiogenic drugs?:

Answer 21

May be useful in preventing metastasis

Use in combo for lower doses with cytotoxics or other anti angio drugs that target a different stage

Question 22

What is the aim of new anti angio therapies

Answer 22

to target newly formed blood vessels - these are leaky and poorly made setting the neovasculare and established vessels appart

Question 23

2e.g of novel anti angi therapies

Answer 23

Vitaxin - antiangiogenic mab against abv3

ANET - antineovascular therapy

Question 24

how does ANET work?

Answer 24

it directs cytotoxic drugs

Question 25

how does ANET work?

Answer 25

it directs cytotoxic drugs
eg adriamycinor dominant molecules
eg mutant Raf to endothelelial cells

Question 26

what is required by antineogenisis therapies

Answer 26

drug delivery systems e.g. liposomes targetted to integrins

Question 27

only endothelial cells have the right TF to express

Answer 27

e-selectin - adhesion molecule

Question 28

concept of gene therapy:

reqiures ……………….. and …………………..

Answer 28

to correct or alleviate disease by delivery of genes

identification of appropriate gene, specific delivery of gene to required area

Question 29

avastin oonly works in what tumours?

Answer 29

those driven by veg f

Question 30

avastin oonly works in what tumours?

Answer 30

those driven by veg f

Question 31

How can we target using E-selectin?

Answer 31

Retroviruses specifically target rapidly proliferating cells

- link this to an endothillial cell specific promoter such as E-selectin or VEG F