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- W408776617 abstract "AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA3054 Nonsteroidal antiinflammatory drugs have proven to be very efficacious to prevent colon cancer in humans and in animal models. They are also very effective chemopreventive agents in experimental animal models of bladder and skin cancer. However the major side effect of such agents is gastrointestinal ulceration and bleeding. Recently it was found that adding a nitrous oxide (NO) group to NSAIDs alleviated this GI toxicity side effect through the protective activity of NO, yet still inhibited cyclooxygenase activity. Our studies were designed to compare the chemopreventive effects of NO-naproxen with the parent compound Naproxen administered in equimolar concentrations in the diet. In the AOM-induced rat colon cancer model Naproxen was administered at 200 and 400 ppm in the diet reduced mean aberrant crypt foci (ACF) in the colon by about 45 and 60% respectively. NO-Naproxen was likewise administered at 300 and 600 ppm by diet and reduced total ACF by 20 and 40% respectively. Importantly, Naproxen and NO-Naproxen at the higher doses reduced multi-crypt foci (4 or more) in colon by 72% and 50%, respectively. In the OH-BBN rat bladder cancer model NO-Naproxen and Naproxen were given at 550 ppm and 400 ppm in the diet respectively. After 6 months the NO-Naproxen group had a 60% decrease in palpable bladder tumors, while the Naproxen group showed a 53% decrease in incidence. These data show that both Naproxen and NO-Naproxen are effective agents against colon and bladder cancers and show similar efficacies. The decrease in gastrointestinal mucosal toxicity seen with the NO-Naproxen would give this agent a distinct advantage in clinical trials for colon or bladder cancer prevention, while the efficacy should be similar to the parent compound. Supported by NCI -CN53300 and CN43301." @default.
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- W408776617 date "2008-05-01" @default.
- W408776617 modified "2023-09-26" @default.
- W408776617 title "Comparative chemopreventive efficacy of Naproxen and NO-Naproxen in rodent models of colon and bladder cancer." @default.
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