MJFDL,
When come to description of the angiogenesis cascade Folkman is master:
First one (few years ago):
1. Fast growing tumor secret ES as natural control of the meth (tumor’s sons) growth???
And now:
2. Direct and indirect angiogenesis inhibitor (Cancer Cell)???
1. Show me clear and ambiguous evidence that ES is secreted by tumor cells?
2. When and where angiogenesis start and when/where end?
If VEGF stimulate and direct EC proliferation and other mechanisms in early neovascularization, than inhibitions of its action is DIRECT inhibition. AS EARLY AS POSIBLE IN PATH!
Or maybe VEGF stimulate HEAR growth, which make man more attractive, which rise women libido, which stimulate man libido, which rise man blood pressure, which ask for more vessels to accommodate blood flow,..which…than maybe VEGF is INDIRECT stimulus for angiogenesis.
<< Q: "I read some abstracts on PubMed that associate *higher* Endostatin levels with a *worse* cancer prognosis. If Endostatin fights cancer, how can this be?"
A: Endostatin is a natural by-product and inhbitor of capillary creation. Therefore, larger, faster-growing tumors put more of it into circulation, despite it being an inhibitor. Dr. Judah Folkman sometimes likes to compare cancer to an infection. If you had a really bad infection, your white blood cell count would be very high. However, everyone agrees that white blood cells fight infection. Amgen even has a blockbuster drug called Neupogen for raising the white blood cell counts of cancer patients who have become susceptible to infection, due to the effects of chemotherapy on bone marrow. In a similar fashion, EntreMed would like to give cancer patients enough Endostatin to stop tumor capillary creation. >>
Yes, ES is BY-PRODUCT? WHEN and WHY?
Where is proof that ES does inhibit capillary creation? Where are studies to explain in details this theory?
What if ES is structural component needed to stabilize new capillaries? And this slow down further remodeling? Why is ES level elevated later, after capillaries are generated, IF IT IS DIRECT INHIBITOR?
Folkman can compare cancer cells with whatever he wants. Does bacteria/virus PRODUCE white blood cells, so they may control own aggressiveness?
Also from Folkman:
ncbi.nlm.nih.gov
<< In tumors grown in SCID mice, endostatin immunostaining was stronger accompanying blood vessel maturation and was significantly prominent in vessels of tumor marginal zone where angiogenesis is highly active. These data indicate a new antiangiogenic action of endostatin stabilizing and maturating endothelial tubes of newly formed blood vessels. Thus, strategies accelerating vascular stabilization and maturation could be promising in tumor therapy.>>
By this it is possible to speculate that at tumor periphery higher level of the ES are needed to stabilize new microvessels. Does this make ES angio-inhibitors?
Also, what plasma ES level is ENOUGH? +1200ng/ml???
I think that we have enough ES discussion? At least I have.
Let first see full PII results?
Miljenko
[EOM] |
