Noor Al-Dasooqi1, Joanne Bowen2, Colin Bennett2, John Finnie3,4, Dorothy Keefe5, Rachel Gibson2. 1. Department of Medicine, University of Adelaide, North Terrace, Adelaide, SA, 5005, Australia. noor.al-dasooqi@adelaide.edu.au. 2. School of Medical Sciences, University of Adelaide, North Terrace, Adelaide, SA, 5005, Australia. 3. SA Pathology, Institute of Medical and Veterinary Science, Frome Rd, Adelaide, SA, 5000, Australia. 4. School of Medical and Veterinary Science, University of Adelaide, North Terrace, Adelaide, SA, 5005, Australia. 5. Cancer Centre, Royal Adelaide Hospital, Adelaide, SA, 5000, Australia.
Abstract
PURPOSE: Chemotherapy-induced mucositis is characterised by damage to mucous membranes throughout the alimentary tract. This study aims to investigate the expression of cell adhesion molecules (CAMs) following treatment with irinotecan. METHODS: Dark agouti rats received a single dose of 175 mg/kg irinotecan and sacrificed at various time points after treatment. Picro-sirius red staining indicated an increase in collagen around crypts from 24 h in both small and large intestinal regions and this diminished at the later time points. CAMs E-cadherin, P-selectin, E-selectin and integrin-α1 were examined using immunohistochemistry. RESULTS: E-cadherin was significantly elevated in jejunal crypts at the time of maximal tissue damage (48 h), while it decreased at the healing phase (96 h) in both jejunum and colon. P-selectin expression decreased significantly in the jejunum following irinotecan. Crypt expression of E-selectin was significantly elevated in the healing phase of mucositis (96 h). Integrin-α1 expression was significantly altered during the time course in the villus (p = 0.0032) and lamina propria (p = 0.039). CONCLUSIONS: Irinotecan induced a significant alteration in CAM expression in the jejunum and colon. Changes in adhesion molecule expression may have a direct impact on the loss of mucosal layer integrity seen in mucositis.
PURPOSE: Chemotherapy-induced mucositis is characterised by damage to mucous membranes throughout the alimentary tract. This study aims to investigate the expression of cell adhesion molecules (CAMs) following treatment with irinotecan. METHODS: Dark agouti rats received a single dose of 175 mg/kg irinotecan and sacrificed at various time points after treatment. Picro-sirius red staining indicated an increase in collagen around crypts from 24 h in both small and large intestinal regions and this diminished at the later time points. CAMs E-cadherin, P-selectin, E-selectin and integrin-α1 were examined using immunohistochemistry. RESULTS:E-cadherin was significantly elevated in jejunal crypts at the time of maximal tissue damage (48 h), while it decreased at the healing phase (96 h) in both jejunum and colon. P-selectin expression decreased significantly in the jejunum following irinotecan. Crypt expression of E-selectin was significantly elevated in the healing phase of mucositis (96 h). Integrin-α1 expression was significantly altered during the time course in the villus (p = 0.0032) and lamina propria (p = 0.039). CONCLUSIONS:Irinotecan induced a significant alteration in CAM expression in the jejunum and colon. Changes in adhesion molecule expression may have a direct impact on the loss of mucosal layer integrity seen in mucositis.
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