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Growth Factor (VEGF) Aids Angiogenesis
February 2, 1999. Because of its role in cancer and other diseases, many groups of researchers are trying to understand what influences and controls the process of angiogenesis (blood vessel growth). A University of Michigan team has found that a natural substance called vascular endothelial growth factor (VEGF) contributes to angiogenesis by helping blood vessels not only to grow but also to live longer.
This finding adds to what's known about how angiogenesis helps tumors spread. It may help researchers develop new strategies for treating angiogenesis-dependent diseases.
Led by Peter Polverini, a professor in the Medical School, the U-M group has been studying the relationship between angiogenesis and programmed cell death (apoptosis), a natural process essential for normal growth and development.
Apoptosis is the process by which the body rids itself of cells it no longer needs -- for example, worn out or damaged cells or cells that have done their jobs and are not longer needed. The researchers showed that VEGF protects blood vessel cells from cell death.
Blood vessel cells in culture normally die when nutrient levels are low. But in the presence of VEGF they were able to survive, apparently because VEGF increases expression of a "survival gene" called Bcl-2. VEGF also induced the cells to organize themselves into vessel-like structures. After seeing this effect in cell culture, the U-M team developed a model system to study how human blood vessels behave inside the body. They mimicked the effect of VEGF by using cells engineered to constantly express the Bcl-2 gene. The engineered cells were first grown on sponges and then transplanted into mice. Again, the cells survived longer and formed more blood vessels than cells that had not been engineered to overexpress the Bcl-2.
The findings may help explain how blood vessels are able to proliferate around tumors, in a toxic, oxygen-deficient environment that isn't normally conducive to cell growth. Through the action of VEGF and Bcl-2, blood vessels are able to grow and survive in this environment, providing an uninterrupted supply of nutrients to the tumor. By understanding this mechanism, researchers may find new ways to starve tumors by inhibiting blood vessel growth.
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(source below P. B25-6 Dr. Strum's book- A Primer on Prostate Cancer):
Here are some know findings on VEGF levels of plasma found with 7.0 pg/ml seems to correspond with localized PCa and 28.5 pg/ml for metastatic PCa. Used statistical analysis says VEGF level of 18 pg/ml was the optimal cut off for differentiating between malignant and localized PCa. Patients with VEGF of >18 pg/ml were 10 times more likely to have mets. So this might be a useful marker of non-organ-confined PCa.
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BCL-2 can be tested for by Dr. Bonkhoff's specialized pathology offerings (fyi)
Drugs that target VEGF include the new in trials XL-184, Tasquinimod (Sweden), (these are in use now)=sunitinib, aflibercept, bevacizumab
This area of PCa is going to get more attention as it seems to another useful way to slow progressions.  Yeah that could be a good thing.
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