title: Activity of the leukotriene pathway in Barrett's metaplasia and oesophageal adenocarcinoma.
abstract: OBJECTIVE
  Leukotriene (LT) B(4) is a lipid inflammatory mediator implicated in tumorigenesis in animal models of Barrett's oesophagitis, but little is known about the cysteinyl-leukotrienes (LTC(4), LTD(4), LTE(4)), which have distinct inflammatory and tumorigenic actions in other tissues. We recently showed that the terminal enzymes for the synthesis of both LT families are highly expressed in human oesophageal adenocarcinoma (OA) tissues. This study therefore examined the capacity of Barrett's metaplasia (BM) and OA tissues to synthesise LTs in vitro.
  
  
  METHODS
  Oesophageal biopsies from patients with BM (n = 14), high-grade dysplasia (n = 2), OA (n = 11), and squamous control tissues (n = 11) were cultured with calcium ionophore A32187 (2 μM) for 60 min. LTB(4) and cysteinyl-leukotrienes were extracted and measured by specific enzyme immunoassays.
  
  
  RESULTS
  Levels of LTB(4) and cysteinyl-leukotrienes were 8.6-fold (P < 0.01) and 2.4-fold (P < 0.02) higher, respectively, in OA tissues than in squamous control tissues, but levels in BM tissues (n = 14) were not altered. Production of the two LT families correlated across all tissue types (r = 0.62, p < 0.00005).
  
  
  CONCLUSIONS
  Increased synthesis of LTB(4) and cysteinyl-leukotrienes has not previously been shown in human OA tissue and our results may indicate a role of these lipids in Barrett's disease progression.
authors.affiliation: Department of Luminal Gastroenterology, University Hospitals Southampton NHS Foundation Trust, Southampton General Hospital, Southampton, UK.
authors.forename: James David
authors.initials: JD
authors.lastname: Shutt
authors.forename: Philip
authors.initials: P
authors.lastname: Boger
authors.forename: James Richard
authors.initials: JR
authors.lastname: Neale
authors.forename: Praful
authors.initials: P
authors.lastname: Patel
authors.forename: Anthony Peter
authors.initials: AP
authors.lastname: Sampson
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism*; D008297:Male; D008679:Metaplasia / Q000378:metabolism; D008875:Middle Aged
chemical_list: D015289:Leukotrienes