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伊立替康引起的黏膜炎:胰高血糖素样肽-2类似物的相互作用及潜在作用

Irinotecan-induced mucositis: the interactions and potential role of GLP-2 analogues.

作者信息

Mayo Bronwen J, Stringer Andrea M, Bowen Joanne M, Bateman Emma H, Keefe Dorothy M

机构信息

School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.

School of Pharmacy and Medical Sciences, Sansom Institute for Health Sciences, University of South Australia, Adelaide, South Australia, Australia.

出版信息

Cancer Chemother Pharmacol. 2017 Feb;79(2):233-249. doi: 10.1007/s00280-016-3165-9. Epub 2016 Oct 21.

Abstract

PURPOSE

A common side effect of irinotecan administration is gastrointestinal mucositis, often manifesting as severe diarrhoea. The damage to the structure and function of the gastrointestinal tract caused by this cytotoxic agent is debilitating and often leads to alterations in patients' regimens, hospitalisation or stoppage of treatment. The purpose of this review is to identify mechanisms of irinotecan-induced intestinal damage and a potential role for GLP-2 analogues for intervention.

METHODS

This is a review of current literature on irinotecan-induced mucositis and GLP-2 analogues mechanisms of action.

RESULTS

Recent studies have found alterations that appear to be crucial in the development of severe intestinal mucositis, including early apoptosis, alterations in proliferation and cell survival pathways, as well as induction of inflammatory cascades. Several studies have indicated a possible role for glucagon-like peptide-2 analogues in treating this toxicity, due to its proven intestinotrophic, anti-apoptotic and anti-inflammatory effects in other models of gastrointestinal disease.

CONCLUSION

This review provides evidence as to why and how this treatment may improve mucositis through the possible molecular crosstalk that may be occurring in models of severe intestinal mucositis.

摘要

目的

伊立替康给药的常见副作用是胃肠道黏膜炎,常表现为严重腹泻。这种细胞毒性药物对胃肠道结构和功能造成的损害使人虚弱,常导致患者治疗方案改变、住院或停止治疗。本综述的目的是确定伊立替康诱导肠道损伤的机制以及胰高血糖素样肽-2类似物在干预中的潜在作用。

方法

这是一篇关于伊立替康诱导的黏膜炎和胰高血糖素样肽-2类似物作用机制的当前文献综述。

结果

最近的研究发现了一些似乎在严重肠道黏膜炎发展中起关键作用的改变,包括早期凋亡、增殖和细胞存活途径的改变,以及炎症级联反应的诱导。几项研究表明,胰高血糖素样肽-2类似物在治疗这种毒性方面可能发挥作用,因为在其他胃肠道疾病模型中已证实其具有肠营养、抗凋亡和抗炎作用。

结论

本综述提供了证据,说明这种治疗为何以及如何通过严重肠道黏膜炎模型中可能发生的分子相互作用来改善黏膜炎。

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