Diet Some common components of human diets also act as mild angiogenesis inhibitors and have therefore been proposed for
angioprevention, the prevention of
metastasis through the inhibition of
angiogenesis. In particular, the following foods contain significant inhibitors and have been suggested as part of a healthy diet for this and other benefits: •
Soy products such as
tofu and
tempeh, (which contain the inhibitor "
genistein") •
Agaricus subrufescens mushrooms (contain the inhibitors
sodium pyroglutamate and
ergosterol) •
Black raspberry (
Rubus occidentalis) extract •
Lingzhi mushrooms (via inhibition of
VEGF and
TGF-beta) •
Trametes versicolor mushrooms (
Polysaccharide-K) •
Maitake mushrooms (via inhibition of
VEGF) •
Phellinus linteus mushrooms (via active substance Interfungins A inhibition of
glycation) •
Green tea (
catechins) •
Liquorice (
glycyrrhizic acid) •
Red wine (
resveratrol) •
Royal jelly (
queen bee acid)
Drugs Research and development in this field has been driven largely by the desire to find better cancer treatments. Tumors cannot grow larger than 2mm without angiogenesis. By stopping the growth of blood vessels, scientists hope to cut the means by which tumors can nourish themselves and thus
metastasize. In addition to their use as anti-cancer drugs, angiogenesis inhibitors are being investigated for their use as
anti-obesity agents, as blood vessels in
adipose tissue never fully mature, and are thus destroyed by angiogenesis inhibitors. Angiogenesis inhibitors are also used as treatment for the wet form of macular degeneration. By blocking VEGF, inhibitors can cause regression of the abnormal blood vessels in the retina and improve vision when injected directly into the
vitreous humor of the eye.
Overview Bevacizumab Through binding to
VEGFR and other VEGF receptors in endothelial cells, VEGF can trigger multiple cellular responses like promoting cell survival, preventing apoptosis, and remodeling
cytoskeleton, all of which promote angiogenesis. Bevacizumab (brand name Avastin) traps VEGF in the blood, lowering the binding of VEGF to its receptors. This results in reduced activation of the angiogenesis pathway, thus inhibiting new blood vessel formation in tumors.
Thalidomide Despite the therapeutic potential of anti-angiogenesis drugs, they can also be harmful when used inappropriately.
Thalidomide is one such antiangiogenic agent. Thalidomide was given to pregnant women to treat nausea. However, when pregnant women take an antiangiogenic agent, the developing fetus will not form blood vessels properly, thereby preventing the proper development of fetal limbs and circulatory systems. In the late 1950s and early 1960s, thousands of children were born with
deformities, most notably
phocomelia, as a consequence of thalidomide use.
Cannabinoids According to a study published in the August 15, 2004 issue of the journal
Cancer Research,
cannabinoids, the active ingredients in
marijuana, restrict the sprouting of blood vessels to gliomas (brain tumors) implanted under the skin of mice, by inhibiting the expression of genes needed for the production of vascular endothelial growth factor (VEGF).
General side effects of drugs Bleeding Bleeding is one of the most difficult side effects to manage; this complication is somewhat inherent to the effectiveness of the drug. Bevacizumab has been shown to be the drug most likely to cause bleeding complications. While the mechanisms of bleeding induced by anti-VEGF agents are complicated and not yet totally understood, the most accepted hypothesis is that VEGF could promote endothelial cell survival and integrity in the adult vasculature and its inhibition may decrease capacity for renewal of damaged endothelial cells.
Increased blood pressure In a study done by ML Maitland, a mean blood pressure increase of 8.2 mm Hg systolic and 6.5 mm Hg diastolic was reported in the first 24 hours after the first treatment with sorafenib, a VEGF pathway inhibitor.
Less common side effects Because these drugs act on parts of the blood and blood vessels, they tend to have side effects that affect these processes. Aside from problems with hemorrhage and hypertension, less common side effects of these drugs include dry, itchy skin, hand-foot syndrome (tender, thickened areas on the skin, sometimes with blisters on palms and soles), diarrhea, fatigue, and low blood counts. Angiogenesis inhibitors can also interfere with wound healing and cause cuts to re-open or bleed. Rarely, perforations (holes) in the intestines can occur. ==See also==