title: Effects of EGFR Inhibitor on Helicobacter pylori Induced Gastric Epithelial Pathology in Vivo.
abstract: Helicobacter pylori transactivates the Epidermal Growth Factor Receptor (EGFR) and predisposes to gastric cancer development in humans and animal models. To examine the importance of EGFR signalling to gastric pathology, this study investigated whether treatment of Mongolian gerbils with a selective EGFR tyrosine kinase inhibitor, EKB-569, altered gastric pathology in chronic H. pylori infection. Gerbils were infected with H. pylori and six weeks later received either EKB-569-supplemented, or control diet, for 32 weeks prior to sacrifice. EKB-569-treated H. pylori-infected gerbils had no difference in H. pylori colonisation or inflammation scores compared to infected animals on control diet, but showed significantly less corpus atrophy, mucous metaplasia and submucosal glandular herniations along with markedly reduced antral and corpus epithelial proliferation to apoptosis ratios. EKB-569-treated infected gerbils had significantly decreased abundance of Cox-2, Adam17 and Egfr gastric transcripts relative to infected animals on control diet. EGFR inhibition by EKB-569 therefore reduced the severity of pre-neoplastic gastric pathology in chronically H. pylori-infected gerbils. EKB-569 increased gastric epithelial apoptosis in H. pylori-infected gerbils which counteracted some of the consequences of increased gastric epithelial cell proliferation. Similar chemopreventative strategies may be useful in humans who are at high risk of developing H.pylori-induced gastric adenocarcinoma.
authors.affiliation: Leeds Institute of Molecular Medicine, St. James's University Hospital, Leeds LS9 7TF, UK. j.crabtree@leeds.ac.uk.
authors.forename: Jean E
authors.initials: JE
authors.lastname: Crabtree
authors.affiliation: Leeds Institute of Molecular Medicine, St. James's University Hospital, Leeds LS9 7TF, UK. Anthony.jeremy@evocutis.com.
authors.forename: Anthony H T
authors.initials: AH
authors.lastname: Jeremy
authors.affiliation: Leeds Institute of Molecular Medicine, St. James's University Hospital, Leeds LS9 7TF, UK. C.Duval@leeds.ac.uk.
authors.forename: Cedric
authors.initials: C
authors.lastname: Duval
authors.affiliation: Department of Pathology, University of Leeds, Leeds LS2 9JT, UK. mikedixon@blueyonder.co.uk.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Dixon
authors.affiliation: Leeds Institute of Molecular Medicine, St. James's University Hospital, Leeds LS9 7TF, UK. kaz.danjo@nifty.com.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Danjo
authors.affiliation: Leeds Institute of Molecular Medicine, St. James's University Hospital, Leeds LS9 7TF, UK. I.M.Carr@leeds.ac.uk.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Carr
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GA, UK. Mark.Pritchard@liverpool.ac.uk.
authors.forename: D Mark
authors.initials: DM
authors.lastname: Pritchard
authors.affiliation: Leeds Institute of Molecular Medicine, St. James's University Hospital, Leeds LS9 7TF, UK.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Robinson