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胃癌的分子病理学:研究与实践。

Molecular pathology of gastric cancer: research and practice.

机构信息

Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Minami-ku, Hiroshima, Japan.

出版信息

Pathol Res Pract. 2011 Oct 15;207(10):608-12. doi: 10.1016/j.prp.2011.09.006. Epub 2011 Oct 17.

Abstract

Recent advances in the understanding of molecular stomach carcinogenesis are reviewed. As to molecular events in individual mucin phenotypes of gastric cancer, the CDX2-Reg IV-SOX9 pathway is associated with the intestinal mucin phenotype, while OLFM4 and CLDN18 are novel markers for the gastric phenotype. microRNAs play an important role in epigenetic deregulation in gastric cancer. Many microRNAs are up-regulated and down-regulated, and some of these are associated with histological differentiation and cancer progression. Reduced miR-200 may participate in the genesis of diffuse type gastric cancer by reducing E-cadherin expression. Genetic polymorphism is a crucial endogenous cause and a fundamental factor of cancer risk. PSCA polymorphism alters the susceptibility to diffuse type gastric cancer through modulation of cell proliferation activity. Cancer stem cells possess the capacity for self-renewal and cause the heterogeneous lineages of cancer cells. Cancer stem cells also show resistance to anti-tumor chemotherapy. Only a minor population of gastric cancer cells reveals the properties of cancer stem cells, and CD44 is one of the markers for gastric cancer stem cells. The origin of gastric cancer stem cells remains to be elucidated.

摘要

本文回顾了对分子胃致癌机制的最新认识。就胃癌个体黏蛋白表型的分子事件而言,CDX2-Reg IV-SOX9 通路与肠型黏蛋白表型相关,而 OLFM4 和 CLDN18 则是胃型的新型标志物。microRNA 在胃癌中的表观遗传失调中发挥重要作用。许多 microRNA 上调和下调,其中一些与组织学分化和癌症进展相关。miR-200 的减少可能通过降低 E-钙黏蛋白的表达参与弥漫型胃癌的发生。遗传多态性是癌症风险的关键内在原因和基本因素。PSCA 多态性通过调节细胞增殖活性改变弥漫型胃癌的易感性。癌症干细胞具有自我更新的能力,并导致肿瘤细胞的异质性谱系。癌症干细胞还表现出对肿瘤化疗的耐药性。只有一小部分胃癌细胞具有癌症干细胞的特性,CD44 是胃癌干细胞的标志物之一。胃癌干细胞的起源仍有待阐明。

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