title: Cyclooxygenase-2 and inflammation mediators have a crucial role in reflux-related esophageal histological changes and Barrett's esophagus.
abstract: BACKGROUND
  Gastroesophageal reflux (GER) causes injury of the esophageal squamous epithelium, a condition called reflux esophagitis. The sequence reflux-esophagitis-intestinal metaplasia-dysplasia-invasive cancer is widely accepted as the main adenocarcinogenetic pathway in the esophagus; however, the mechanisms of this progression need to be better defined.
  
  
  OBJECTIVE
  We evaluated COX-2 expression and activity in biopsies from patients affected with GER, and these parameters have been correlated with the stage of the disease, ceramide expression, apoptotic process, and angiogenesis. The effects of celecoxib on bile acid- and EGF-induced mucosal proliferation, apoptosis and angiogenesis have been also investigated.
  
  
  METHODS
  Four groups of patients were distinguished: non esophagitis, non erosive esophagitis, erosive esophagitis, and Barrett's esophagus. COX-2 expression, basal PGE2 levels, proliferative activity, VEGF expression and apoptosis were evaluated in esophageal biopsies.
  
  
  RESULTS
  COX-2 expression, basal PGE2 levels, proliferative activity, VEGF expression and apoptosis progressively increase from non esophagitis patients to patients with non erosive and erosive esophagitis, to those with BE. Incubation of the cells with DCA/EGF increases PGE2 production, proliferative activity and VEGF production, effects prevented by celecoxib pretreatment. Ceramide expression increased from non esophagitis patients to patients with non erosive and erosive esophagitis, and decreased in BE; caspase-3 activity progressively decreased from non esophagitis to BE patients, suggesting an impairment of the apoptotic process with disease progression.
  
  
  CONCLUSIONS
  These results stand for a close relationship between progression of initial steps of gastroesophageal reflux disease (GERD) and COX-2, proliferative activity and EGF/VEGF expression and could have implications in GERD treatment in order to prevent its neoplastic evolution.
authors.affiliation: Department of Surgery and Translational Medicine, Section of General Surgery, University of Florence-Careggi General Hospital, AOU Careggi, Largo Brambilla n. 3, 50134, Florence, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Taddei
authors.forename: Valentina
authors.initials: V
authors.lastname: Fabbroni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pini
authors.forename: Laura
authors.initials: L
authors.lastname: Lucarini
authors.forename: Maria Novella
authors.initials: MN
authors.lastname: Ringressi
authors.forename: Ornella
authors.initials: O
authors.lastname: Fantappiè
authors.forename: Daniele
authors.initials: D
authors.lastname: Bani
authors.forename: Luca
authors.initials: L
authors.lastname: Messerini
authors.forename: Emanuela
authors.initials: E
authors.lastname: Masini
authors.forename: Paolo
authors.initials: P
authors.lastname: Bechi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology*; D001706:Biopsy; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002518:Ceramides / Q000235:genetics / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D004947:Esophagus / Q000473:pathology*; D005260:Female; D005764:Gastroesophageal Reflux / Q000378:metabolism / Q000473:pathology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D002518:Ceramides; D019394:Ki-67 Antigen; D042461:Vascular Endothelial Growth Factor A; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D053148:Caspase 3; D015232:Dinoprostone