Angiogenesis

Question 1

What are the two general ways in which heparin facilitates angiogenesis?

Answer 1

1. It enhances capillary endothelial cell movement.

2. It enhances the effect of certain endothelial growth factors

Question 2

Why is heparin present near sites of angiogenesis?

Answer 2

Because there is frequently inflammation, and thus mast cells. The mast cells contain the heparin.

Question 3

What is the previously unknown function of heparin that allows it to act as a regulator of angiogenesis?

Answer 3

It binds the endothelial growth factors needed.

Question 4

What is the major growth factor that regulates angiogenesis/

Answer 4

VEGF

Question 5

What are the major stimuli of angeiogenesis?

Answer 5

VEGF
Hypoxia
PDGF
Angiopoietins

Question 6

When does angiogenesis occur?

Answer 6

Growth and differentiation
Wound repair
Endometrial and placental growth
Tumor Growth
Retinopathies

Question 7

What are the steps of capillary formation?

Answer 7

Angiogenic signals are present. Endothelial cells degrade the vascular basement membrane by MMPs. Endothelial cells migrate, forming tip cells, that migrate toward the stimulus. Cell proilferation forms a lumen. The lumen extends toward angiogenic signals. The sprout fuse togther.

Question 8

What does paracrine mean?

Answer 8

Secretion of factors (such as VEGF) that affect local tissues

Question 9

What are the growth factors used in neovascularization

Answer 9

VEGF, PDGF, EGF

Question 10

What immune system is cell is commonly found in sites of neovascul.?

Answer 10

Mast Cells

Question 11

What chemical do mast cells release that plays a key role in neovascul.?

Answer 11

Heparin

Question 12

How does heparin assist in neovascul.?

Answer 12

Heparin has high affinity binding receptors for VEGF. Heparin also binds to endothelial cells, allow the VEGF to have a prolonged effect in the area.

Question 13

What is the difference between angiogenesis and arteriogenesis?

Answer 13

Angiogenesis is capillary sprouting, resulting in higher capillary density.

Arteriogenesis is rapid proliferation of collateral arteries.

Question 14

What are two strategies for inhibiting pathologic angiogenesis?

Answer 14

Inhibition of tumor endothelial proliferation

Vascular normalization

Question 15

What is angiogenic switch?

Answer 15

Angiogenesis consists of a balance of positive and negative signals. Tumors, once they begin to experience hypoxia, switch the producing more positive signals (such as VEGF) to allow continued existence.

Question 16

What is refractoriness?

Answer 16

The tumor gene becomes resistant to anti-VEGF therapy

Question 17

What is the role of transcription factors in pro-angiogenesis?

Answer 17

During hypoxia, HIF stabilization and transactivation of the promoters of target genes such as VEGF. HIF inhibitino could be a new way of anti-angiogenic therapy.

Question 18

How does hypoxia inducible factor work?

Answer 18

Hypoxia activates HIFs, which upregulate expression of VEGF gene.

Question 19

Why is the treatment with anti-VEGF therapies sometimes refractory?

Answer 19

I dont know…

Question 20

What is the role of guidance signals in angiogenesis?

Answer 20

They signal to the tip cell of the growing capillaries where to go.

Question 21

What is the evidence that cancer grwoth is angiogenesis-dependent?

Answer 21

When cancers are grown extracellularly, they did not stay alive. In contrast, when put into mice, they lived because they grew oxygen-drawing vessels.

Question 22

What is bevacizumab?

Answer 22

A monoclonal antibody directed against VEGF .

Question 23

What is the paradox of vascular normalization that makes combination therapy of VEGF blockade and chemotherapy more effective?

Answer 23

VEGF blockade results in temporary normalization of tumor vasculature because it selectively prunes poorly formed vessels, allowing a return to normal bp in well-formed tumor vessels. This, then allows the chemotherapy to be more effectively delivered to the tumor.

Question 24

What is the drawback of using anti-VEGF therapy on its own?

Answer 24

When drug therapy is stopped, revascularization occurs rapidly using skeletal remains of previously vessels.

Question 25

Why is HIF inhibition a difficult process to address?

Answer 25

The HIF stabilization is very intact. Also, there is currently no known therapeutic agent that inhibits their stabilization.

Question 26

What are TKIs?

Answer 26

Tyrosine Kinase Inhibitors that selectively inhigibt TK domains of EGFR.

Question 27

Why are TKIs second-line therapies?

Answer 27

I don’t know