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Antiangiogenic therapy produces liver injury in treated animals.
2003 AUG 7 - (NewsRx.com & NewsRx.net) -- by Sonia Nichols, senior medical writer - Recent studies of a therapy designed to suppress tumor angiogenesis show it causes liver injury in research animals.
According to medical investigators at the University of Alabama in Birmingham, the adenovirus-mediated therapy delivers soluble FLT-1 (sFLT-1) gene to the liver when administered systemically to mice implanted with human ovarian cancer tumors. Soluble FLT-1 is a vascular endothelial growth factor antagonist.
VEGF encourages angiogenesis, or the growth of new blood vessels, in tumors. These vessels foster tumor growth and metastasis. In an earlier study, UAB investigators examined local delivery of sFLT-1 gene therapy to ovarian tumors. In a current study, they looked at whether or not intravenous (i.v.) systemic delivery would better facilitate its delivery to metastatic lesions.
For the study, sets of mice engrafted with human ovarian tumors in their abdominal cavities received s-FLT1 gene therapy incorporating the reporter molecule green fluorescent protein (GFP) (AdRGDGFPsFLT-1), adenovirus encoded for GFP only (AdRGDGFP), or injections of phosphate buffered saline. Researchers then based therapeutic efficacy on mouse longevity. Subsequent i.v. or intraperitoneal (i.p.) injections of the same three agents to non-tumor bearing mice were used for assessing drug safety.
According to Parameshwar J. Mahasreshti and colleagues, study data showed that animals treated with i.v. AdRGDGFPsFLT-1 actually did not live as long as their control-treated counterparts.
"Furthermore, in the safety evaluation ...
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Source: HighBeam Research, Antiangiogenic therapy produces liver injury in treated animals.