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dc.contributor.authorMayo, B.en
dc.contributor.authorStringer, A.en
dc.contributor.authorBateman, E.en
dc.contributor.authorBowen, J.en
dc.contributor.authorWignall, A.en
dc.contributor.authorWozniak, B.en
dc.contributor.authorWhite, I.en
dc.contributor.authorPietra, C.en
dc.contributor.authorCantoreggi, S.en
dc.contributor.authorKeefe, D.en
dc.identifier.citationAsia-Pacific Journal Of Clinical Oncology, 2014 / vol.10, iss.Suppl. 8, pp.134en
dc.description.abstractIntroduction: Gastrointestinal mucositis (GIM) is a severe and debilitating side-effect of cancer therapy. There are currently few treatments which effectively prevent or ameliorate GIM. In a previous study it was shown that elsiglutide, a selective glucagon-like peptide-2 (GLP-2) receptor agonist, improved diarrhoea and histological damage associated with irinotecaninduced GIM in a rat model. Increased apoptosis, inflammation and decreased proliferation are associated with irinotecan-induced GIM. It is thought that elsiglutide may improve diarrhoea and damage through altering these gastrointestinal cellular effects. Objectives: To determine if elsiglutide reduces apoptosis and inflammation, and increases proliferation in the small intestinal crypts of the rat, following irinotecan administration. Method: Dark Agouti rats were given irinotecan once (200 mg/kg, 0 hrs) and elsiglutide (0.9 mg/kg or 1.8 mg/kg per day, subcutaneous) for 5 days, and killed at 6, 72 or 120 hrs (n = 6). Markers for apoptosis (Caspase-3), proliferation (Ki67) and inflammation (myeloperoxidase, MPO) were analysed using immunohistochemistry in the jejunum and ileum. Positive stained cells were counted per crypt or field of view (FOV). Results: Apoptosis was significantly (p < 0.05, cells/crypt) reduced following 0.9 mg/kg/day elsiglutide and irinotecan at 6 hrs (Jejunum 10.15 ±1.00; Ileum 13.85 ± 1.44) compared with irinotecan control (Jejunum 14.84 ±1.15; Ileum 22.49 ± 1.08). Proliferation was significantly (p < 0.05, cells/demi-crypt) increased at 72 hrs (peak damage) in this group (Jejunum 31.45 ± 2.78; Ileum 28.47 ± 2.64) compared with irinotecan alone (Jejunum 18.98 ± 2.13; Ileum 18.64 ± 1.62). Staining also showed that 0.9 mg/kg/day elsiglutide given after irinotecan significantly (p < 0.01, cells/FOV) reduces the number of MPO positive inflammatory cells in the jejunum (72 hrs 67.02 ± 6.72; 120 hrs 42.08 ± 5.52) compared with irinotecan alone (72 hrs 106.69 ±6.04; 120 hrs 64.30 ± 7.65). Conclusions: Elsiglutide (0.9 mg/kg/day) decreases apoptosis and inflammation, which may be contributors to irinotecan-induced GIM. In addition, elsiglutide improves proliferation of crypt cells, which may shorten the duration of GIM. These results provide a basis for future studies with elsiglutide to determine the exact mechanisms for this phenomenon.en
dc.description.statementofresponsibilityBronwen Mayo, Andrea Stringer, Emma Bateman, Joanne Bowen, Anthony Wignall, Belinda Wozniak, Imogen White, Claudio Pietra, Sergio Cantoreggi, Dorothy Keefeen
dc.rights© 2014 The Authors. Asia-Pacific Journal of Clinical Oncology © 2014 Wiley Publishing Asia Pty Ltden
dc.titleApoptosis, proliferation and inflammation are improved after treatment with the new selective glp-2 receptor agonist, elsiglutide, in a rat model of irinotecan-induced mucositisen
dc.typeConference itemen
dc.contributor.conferenceCOSA's 41st Annual Scientific Meeting. Joining Forces - Accelerating Progress (02 Dec 2014 - 04 Dec 2014 : Melbourne, Vic.)en
dc.identifier.orcidStringer, A. [0000-0003-3245-5360]en
dc.identifier.orcidBateman, E. [0000-0003-1665-102X]en
dc.identifier.orcidBowen, J. [0000-0003-0876-0031]en
dc.identifier.orcidKeefe, D. [0000-0001-9377-431X]en
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