�In a landmark work, Medical College of Wisconsin researchers in Milwaukee written report that drugs used to inhibit a specific fat person acid in rat brains with glioblastoma-like tumors non only reduced new blood vessel growth and tumor size dramatically, but as well prolonged survival. The study is the featured cover story of the August, 2008 Journal of Cerebral Blood Flow & Metabolism.
"These rat example tumors were developed from human glioblastoma tumor cells and closely mimic human tumors in growth patterns and response to therapy," says leash researcher David Harder, Ph.D., Kohler Co. Professor in Cardiovascular Research. "The construct of targeting blood vessels that feed tumors as an approach to limit tumor growth is non a novel idea," he says. "However, blocking the specific butterball acid described in this study is novel, and holds great promise for use in humans."
Malignant gliomas are very aggressive tumors of the central nervous system, resistant to chemotherapy and radiation, and account for around half of the 350,000 head tumors currently diagnosed in the U.S.
Dr. Harder is also prof of physiology, associate dean for research and director of the Medical College's Cardiovascular Research Center. He believes that further studies, demonstrating that such drugs work in humans may reveal that higher concentrations or infusions over thirster periods of time may be more effective than the results reported in this study.
"If survival time could be extended, with a combination of surgical therapy and infusion with similar drugs, this could be a significant treatment option," he says.
Earlier studies from the Harder science lab have shown that specific fatty acids generated in the brain induce new blood vessel growth known as angiogenesis. Harder and colleagues designed these studies on the premise that all cells, including genus Cancer cells, ask oxygen for growth and that block formation of specific roly-poly acids would decrease blood vessel growth and atomic number 8 supply to tumors, retarding their growth.
In their current study, Dr. Harder and colleagues compared three sets of rats with induced tumors, 2 groups victimization either one of two inhibitor drugs, 17-ODYA or miconazole, to block the fatty acid CYP epoxygenase and a control radical, receiving a placebo. Drugs were infused directly into the tumors over an extended period of time, using specially-designed miniature osmotic pumps and a very small burr hole in the skull. The pumps, similar to those put-upon in mankind, were interred just to a lower place the skin through a tiny incision.
Compared to the control group, tumor size in the drug-infused groups was rock-bottom by an average 50 to 70 percent, and survival time increased by five to seven years, equivalent to three to four months in footing of human survival.
"These pumps have been used in humans for other diseases and canful be designed for bringing of these drugs as well," says Dr. Harder. "We believe they tin be used to render drugs to block angiogenesis in complex human tumors such as glioblastomas."
Dr. Harder's co-investigators in this sketch were Debebe Genremedhin, Ph.D., associate prof of physiology, and Medical College postdoc fellows Drazen Zagorac, Ph.D. and Danica Jakovcevic, Ph.D.
The study was funded by the National Heart Lung and Blood Institute of the National Institutes of Health, and the Department of Veterans Affairs Administration.
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