Rapid CommunicationsGene therapy for gastric ulcers with single local injection of naked DNA encoding VEGF and angiopoietin-1☆,☆☆
Section snippets
Experimental ulcer model
This study was approved by the subcommittee for animal studies of the Long Beach (California) Department of Veterans Affairs Medical Center. Male Sprague-Dawley rats (200-225 g in weight) were used. Rats fasted for 12 hours underwent laparotomy under nembutal anesthesia (50 mg/kg body weight). One hundred percent acetic acid (50 μL) was applied to the serosa of glandular stomach at the anterior wall through a polyethylene tube (4.0 mm inner diameter) for 90 seconds. The acetic acid was removed
Results
At 7 days, no significant difference was discernable in ulcer size or macroscopic appearance between rats injected with either plasmid-encoding rhVEGF165 or plasmid-encoding rhAng1 and rats injected with a nonexpressing control plasmid. This is not unexpected because the ulcer healing process follows the normal ulcer healing curve phases consisting of an early lag phase, a rapid healing phase, a late lag phase, and a remodeling phase.12 Therefore, at 7 days, differences cannot be detected. In
Discussion
Gene therapy has shown only limited efficacy for treatment of congenital diseases mainly caused by temporary gene expression and adverse host-immune responses. However, temporary gene expression locally in cells involved in the ulcer healing process is ideal for treatment of chronic ulcers where temporary gene activation is beneficial. The critical requirement for angiogenesis during the healing of chronic gastric injury appears to make VEGF, the most potent angiogenic factor, an ideal
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Address requests for reprints to: Andrzej S. Tarnawski, M.D., D.Sc., Professor of Medicine, Chief, Division of Gastroenterology, University of California, Irvine and VA Medical Center, Long Beach (CA), 5901 East Seventh Street, Long Beach, California 90822. e-mail: [email protected]; fax: (562) 494-5675.
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Supported by a VA Merit Review (AST) and Research Enhancement Award Programs.