Lecture 9

Question 1

Do blood vessels grow into the tumor?

Answer 1

No, they do not like hypoxia, so the stay on the outside and grow around it

Question 2

Can blood vessels be in tumors though?

Answer 2

Yes, they can be engulfed into tumors when they grow

Question 3

Which different types of blood vessel formation are there?

Answer 3

Vasculogenesis, arteriogenesis and angiogenesis

Question 4

How does vasculogenesis in development work?

Answer 4

Angioblasts form vessels from progenitor cells by fusing them together

Question 5

How does vasculogenesis work in adults?

Answer 5

Cells from the blood marrow go into the blood stream using ECFC and CFU-EC (both are endothelial progenitor cells), where ECFC builds and CFU-EC supports

Question 6

What is the function of Angiogenesis?

Answer 6

To form new vessels from existing ones by ECFC adherence and proliferation

Question 7

What is the consequence of higher shear stress?

Answer 7

The adhesion molecule ICAM-1 is expressed on endothelial cells, this binds to Mac-1 on monocytes. And then monocytes are transformed to macrophages

Question 8

What does ischemia induce?

Answer 8

Inflammtion

Question 9

What can inflammation induce?

Answer 9

Angiogenic growth factors

Question 10

How does developmental angiogenesis happen?

Answer 10

Areas get hypoxic when you grown, thus new vessels are needed

Question 11

What is physiological angiogenesis?

Answer 11

eg the female reproductive system and normal wound healing

Question 12

What is repair associated/ pathiological angiogenesis?

Answer 12

Chronic wound healing, tumor growth, arthritis, diabetic retinopathy

Question 13

Which two molecules can a tumor induce?

Answer 13

Inflammatory mediator and angiogenic GF

Question 14

What is the function of inflammatory mediator and angiogenic growth factor?

Answer 14

it activates endothelial fibrin and forms fibrinous exudate, which can make new blood vessels.

Question 15

How can the vessels be stabilized?

Answer 15

By pericytes and smooth muscle or fibrin removal

Question 16

What is the function of uPAR?

Answer 16

It binds to uPA

Question 17

What does uPA do?

Answer 17

It activates plasmin, which in its turn breaks down ECM proteins.

Question 18

What is the break down of ECM proteins needed for?

Answer 18

For invasion to be possible

Question 19

What is quiesence?

Answer 19

When the positive and negative regulators of angiogenesis are in balance

Question 20

What is the function of VEGF (Vascular Endothelial GF)?

Answer 20

It is pro-angiogenic

Question 21

Which different VEGFs are there?

Answer 21

normal VEGF (or VEGF A), VEGF B, VEGF C, VEGF D, VEGF E (musquitos), PLGF (placenta)

Question 22

What is the role of VEGFR 1 and 2?

Answer 22

They have a role in angiogenesis and vasculogenesis

Question 23

What is the role of VEGFR 3?

Answer 23

It has a role in lymphangiogenesis and angiogenesis

Question 24

Where can VEGFR 1 be found and what function does it have?

Answer 24

It can be found on endothelium and monocytes and has a migration function

Question 25

Where can VEGFR 2 be found and what function does it have?

Answer 25

It can be found on endothelium and has a role in proliferation, migration and permeability

Question 26

Where can VEGFR 3 be found and what function does it have?

Answer 26

It can be found on lymphatic endothelium and has a role in migration and proliferation

Question 27

How many VEGFRs are needed to activate endothelial cells?

Answer 27

two

Question 28

How can VEGFR be activated?

Answer 28

By binding of VEGF to the tyrosine kinase of receptors, which then cross-link and phosphorylate, then eventually there is angiogenesis

Question 29

What are tip cells and what is their function?

Answer 29

These are endothelial cells that form a tip to penetrate into tissue (have a high expression of VEGFR2), they send a signal to neighbouring cells that they cannot become a tip cell

Question 30

What are stalk cells?

Answer 30

Neighbouring cells of the tip cell that will migrate with them

Question 31

What are phalanx cells?

Answer 31

Cells in the stable vessels that do not proliferate anymore

Question 32

What happens to the blood vessels in the eyes of diabetic patients?

Answer 32

They are increased in number

Question 33

What does the VEGF signal lead to?

Answer 33

Permeability, migration, proliferation and survival of endothelial cells

Question 34

What are inhibitors of VEGF?

Answer 34

Remove it using antibodies (eg bevacizumab) Block receptors (eg ramucirumab) Chemical tyrosine kinase inhibitor (its not specific though)

Question 35

What is IFL?

Answer 35

Irinotecan, which is a type of chemo

Question 36

Why does anti-VEGF (antibodies) show disappointing results?

Answer 36

Other pro-angiogenic molecules are produced by the tumor that are not inhibited

Question 37

What can normalizing or stimulating the vasculature lead to?

Answer 37

An increased effect of chemo. More oxygen in the tumor, which will lead to a better response to radiation More immune cells

Question 38

What is age-related macular degeneration?

Answer 38

There is blood in the eye at the macula. You can either get the wet or the dry form

Question 39

How can the wet form of macular degeneration be helped?

Answer 39

By injecting an anti-VEGF into the eye, which reduces the blood vessels and their permeability. Improves 30-35%

Question 40

What are side effects of an anti-VEGF antibody?

Answer 40

Gastrointestinal perforation, bleeding, delayed wound healing, hypertension and thrombonic effect

Question 41

What do gastrointestinal perforation, bleeding and delayed wound healing affect?

Answer 41

Survival and have less endothelial cells

Question 42

What causes hypertension?

Answer 42

Less NO

Question 43

What is the thrombonic effect?

Answer 43

There is more trauma as vessels die, thus more thrombin is produced

Question 44

How can anti-VEGF also result in lower thrombin?

Answer 44

If there is more tissue factor, which will only be true when there is no trauma