title: Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus.
abstract: OBJECTIVE
  Carcinogenesis in Barrett's esophagus (BE) is associated with an increased expression of cyclooxygenase (COX) 2. However, there has been no direct evidence that inhibition of COX-2 prevents cancer in BE. We studied the effect of MF-Tricyclic, a selective COX-2 inhibitor, on the development of BE and adenocarcinoma in a rat model.
  
  
  METHODS
  Four weeks after esophagojejunostomy, 105 Sprague-Dawley rats were randomized to a chow containing MF-Tricyclic or Sulindac, or a placebo. Ninety-six (92%) rats completed the study and were sacrificed at 28 +/- 2 weeks. The animals were assessed for the presence of cancer, tumor volume, BE, degree of inflammation, and COX-2 expression and activity.
  
  
  RESULTS
  MF-Tricyclic and Sulindac reduced the relative risk of development of esophageal cancer by 55% (95% confidence interval [CI] = 43%-66%, P < 0.008) and by 79% (95% CI = 68%-87%, P < 0.001), respectively, compared with controls. No significant differences were noted in the risk of esophageal cancer between the MF-Tricyclic and the Sulindac group (P = 0.34). The median tumor volume was not significantly different among the 3 groups (P = 0.081). Moderate to severe degree of inflammation was significantly more common (P = 0.005) in the control compared with the MF-Tricyclic and the Sulindac group; however, the prevalence of BE was not significantly different between groups (P = 0.98). Rats in the control group had higher tissue PGE2 level compared with the MF-Tricyclic and Sulindac groups (P = 0.038).
  
  
  CONCLUSIONS
  Selective and nonselective COX-2 inhibitors can inhibit inflammation, COX-2 activity, and development of adenocarcinoma induced by reflux. This provides direct evidence that COX-2 inhibitors may have chemopreventive potential in BE.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Hepatology, Mayo Graduate School of Medicine, Rochester, Minnesota, USA.
authors.forename: Navtej S
authors.initials: NS
authors.lastname: Buttar
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Wang
authors.forename: Olga
authors.initials: O
authors.lastname: Leontovich
authors.forename: Jay Y
authors.initials: JY
authors.lastname: Westcott
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Pacifico
authors.forename: Marlys A
authors.initials: MA
authors.lastname: Anderson
authors.forename: Krishnawatie K
authors.initials: KK
authors.lastname: Krishnadath
authors.forename: Lori S
authors.initials: LS
authors.lastname: Lutzke
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Burgart
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D001471:Barrett Esophagus / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000097:blood / Q000494:pharmacology; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004941:Esophagitis / Q000150:complications / Q000473:pathology; D005663:Furans / Q000097:blood / Q000494:pharmacology; D005764:Gastroesophageal Reflux / Q000150:complications / Q000473:pathology; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D007783:Lactones / Q000097:blood / Q000494:pharmacology; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005663:Furans; D007527:Isoenzymes; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; C102563:3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2(5H)-furanone; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases