Crabtree, JE, Jeremy, AHT, Duval, C et al. (5 more authors) (2013) Effects of EGFR inhibitor on helicobacter pylori induced gastric epithelial pathology in vivo. Pathogens, 2 (4). 4. 571 - 590. ISSN 2076-0817
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2013, The Authors. This is an Open Access article distributed in accordance with the Creative Commons Attribution (CC BY 3.0) licence, which permits others to distribute, remix, adapt, build upon this work, and license their derivative works on different terms, provided the original work is properly cited. |
Keywords: | Helicobacter pylori; EGFR inhibitor; EKB-569; epithelial cell proliferation; apoptosis |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Genetics, Health and Therapeutics (LIGHT) > Academic Unit of Cardiovascular Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 27 Mar 2015 10:48 |
Last Modified: | 05 Nov 2017 11:56 |
Published Version: | http://dx.doi.org/10.3390/pathogens2040571 |
Status: | Published |
Publisher: | MDPI |
Identification Number: | 10.3390/pathogens2040571 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:83625 |