gdpawel
Senior User
Joined: 15 Jan 2005
Posts: 125
Location: Pennsylvania
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 Posted: Wed Nov 02, 2005 10:23 am Post subject: Avastin as a single agent |
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Cell culture detection of microvascular cell death in clinical specimens of human neoplasms and peripheral blood can identify the activity of both single drugs and combinations of drugs at the level of individual patients with individual cancers. It works by measuring drug effects (real-time) upon endothelial cells which make up blood vessels.
Drugs like Avastin have striking anti-microvascular effects but minimal anti-tumor effects.
Conclusions of a study published in the Journal of Internal Medicine had shown that Avastin + Tykerb may be the first clinically-exploitable antivascular drug combination. High dose, intermittent 'bolus' schedules of Tykerb to coincide with Avastin administration may be clinically advantageous.
The system utilized for the study was a functional profiling assay, which may be used to individualize antivascular therapy. It can be adapted for simple, inexpensive and sensitive/specific detection of tissue and circulating microvascular cells in a variety of neoplastic and non-neoplastic conditions and individualized cancer treatment.
The cell-based assay can accurately sort drugs into categories of above average probability of providing clinical benefit on one hand and below average probability of providing clinical benefit on the other hand, based both on tumor response and patient survival.
A private lab in the U.S. has worked with the use of DMSO and alcohol as an anti-angiogenic enhancer and potentiator and has actually measured it with "live" tumor specimens in cell culture assays.
Either oral DMSO or high dose oral alcohol (as in one and a half bottles or red wine per day for 4 days) can have a beneficial affect on cancer cells when mixed with anti-angiogenesis drugs like Avastin.
Avastin directly binds to VEGF to directly inhibit angiogenesis. Within 24 hours of VEGF inhibition, endothelial cells have been shown to shrivel, retract, fragment and die by apoptosis. Tumors which secrete relatively low levels of VEGF might be more susceptible to an agent like Avastin which works by blocking VEGF and inhibits the formation of new blood vessels.
Avastin, with alcohol (as an anti-angiogenic enhancer and potentiator), the abrogating effect of the alcohol upon VEGF reduces the secretion of VEGF by the tumor cells. It both reduces VEGF and makes Avastin work better, possibly overcoming tumor resistance to Avastin.
It is thought that the alcohol has has a membrane effect, basically putting the cells to sleep so that it doesn't think it requires a blood supply. In the presence of Avastin, it has a lethal 1-2 combination which knocks out the new vessels which are dependent on VEGF for survival.
Literature Citation: Weisenthal, LM, Patel, N, and Rueff-Weisenthal, C. Cell culture detection of microvascular cell death in clinical specimens of human neoplasms and peripheral blood. J Intern Med 264:275-287, September 2008 |
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