Prevention of chemically induced urinary bladder cancers by naproxen: protocols to reduce gastric toxicity in humans do not alter preventive efficacy

Cancer Prevention Research
Ronald A LubetC J Grubbs

Abstract

The COX inhibitors (NSAID/Coxibs) are a major focus for the chemoprevention of cancer. The COX-2-specific inhibitors have progressed to clinical trials and have shown preventive efficacy in colon and skin cancers. However, they have significant adverse cardiovascular effects. Certain NSAIDs (e.g., naproxen) have a good cardiac profile, but can cause gastric toxicity. The present study examined protocols to reduce this toxicity of naproxen. Female Fischer-344 rats were treated weekly with the urinary bladder-specific carcinogen hydroxybutyl(butyl)nitrosamine (OH-BBN) for 8 weeks. Rats were dosed daily with NPX (40 mg/kg body weight/day, gavage) or with the proton pump inhibitor omeprazole (4.0 mg/kg body weight/day) either singly or in combination beginning 2 weeks after the final OH-BBN. OH-BBN-treated rats, 96% developed urinary bladder cancers. While omeprazole alone was ineffective (97% cancers), naproxen alone or combined with omeprazole-prevented cancers, yielding 27 and 35% cancers, respectively. In a separate study, OH-BBN -: treated rats were administered naproxen: (A) daily, (B) 1 week daily naproxen/1week vehicle, (C) 3 weeks daily naproxen/3 week vehicle, or (D) daily vehicle beginning 2 weeks after last OH-BBN treat...Continue Reading

References

Apr 1, 1997·Clinical Pharmacokinetics·N M Davies, K E Anderson
May 23, 1998·Annual Review of Pharmacology and Toxicology·J R VaneR M Botting
Apr 1, 2003·Advances in Experimental Medicine and Biology·Deborah W KnappAmalia E DeGortari
Sep 1, 2006·The New England Journal of Medicine·Monica M BertagnolliUNKNOWN APC Study Investigators
May 15, 2007·Lancet·James M Scheiman, A Mark Fendrick
Sep 19, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Konstantin ChristovRonald A Lubet
Aug 2, 2008·Neoplasia : an International Journal for Oncology Research·Paul D WilliamsDan Theodorescu
Aug 21, 2008·International Journal of Cancer. Journal International Du Cancer·Ronald A LubetClinton J Grubbs
Jun 10, 2010·Circulation. Cardiovascular Quality and Outcomes·Emil Loldrup FosbølGunnar H Gislason
Dec 1, 2010·Journal of the National Cancer Institute·Craig A ElmetsGary B Gordon
Mar 4, 2011·American Journal of Epidemiology·Sarah E DaughertyDebra T Silverman
Mar 17, 2011·The American Journal of Gastroenterology·Elizabeth H RuderAmanda J Cross
May 4, 2011·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Paul W ElsinghorstFritz Sörgel
Jul 23, 2011·Cancer Prevention Research·Susan M FischerRonald A Lubet
Sep 2, 2011·Cancer Prevention Research·Anita L SabichiSeth P Lerner
Oct 1, 2011·Journal of the National Cancer Institute·Mitch DowsettUNKNOWN International Ki-67 in Breast Cancer Working Group

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Citations

Sep 11, 2016·Materials Science & Engineering. C, Materials for Biological Applications·Raj KumarFarideh Javid
Mar 23, 2017·Photochemistry and Photobiology·Sandeep C ChaudharyMohammad Athar
Apr 26, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Altaf MohammedMark Steven Miller

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