title: Chemoprevention of OH-BBN-induced bladder cancer in mice by piroxicam.
abstract: Piroxicam inhibited induction of transitional cell carcinoma in mouse urinary bladder by N-butyl-N-(4-hydroxybutyl)-nitrosamine. At 15 mg piroxicam/kg diet, tumor incidence was reduced 82% (P < 0.0001) compared with carcinogen controls. At 30 mg piroxicam/kg diet, tumor incidence was reduced 70% (P < 0.001). Results at the higher dose level suggested that piroxicam also may have inhibited invasion slightly. Combination treatment with 2-difluoromethyl-ornithine (DFMO) or all-trans-N-(4-hydroxyphenyl)retinamide (4-HPR) or both agents did not improve the chemopreventive potential of piroxicam. However, the three-agent combination of 30 mg piroxicam/kg, 1200 mg DFMO/kg and 313 mg 4-HPR/kg diet was highly effective. Tumor incidence was reduced 91% (P < 0.0001) compared with carcinogen controls. Unfortunately, the high efficacy was somewhat compromised by a significant decrease in survival and body weight gain in mice receiving the combination of agents compared with the carcinogen control.
authors.affiliation: IIT Research Institute, Chicago, IL 60616.
authors.forename: R C
authors.initials: RC
authors.lastname: Moon
authors.forename: G J
authors.initials: GJ
authors.lastname: Kelloff
authors.forename: C J
authors.initials: CJ
authors.lastname: Detrisac
authors.forename: V E
authors.initials: VE
authors.lastname: Steele
authors.forename: C F
authors.initials: CF
authors.lastname: Thomas
authors.forename: C C
authors.initials: CC
authors.lastname: Sigman
mesh_terms: D000818:Animals; D002085:Butylhydroxybutylnitrosamine; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000517:prevention & control*; D004357:Drug Synergism; D000518:Eflornithine / Q000494:pharmacology; D017313:Fenretinide / Q000627:therapeutic use; D008297:Male; D051379:Mice; D010894:Piroxicam / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D010894:Piroxicam; D017313:Fenretinide; D002085:Butylhydroxybutylnitrosamine; D000518:Eflornithine