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微管的动态重组与胶质瘤侵袭

Dynamic Reorganization of Microtubule and Glioma Invasion.

作者信息

Otani Yoshihiro, Ichikawa Tomotsugu, Kurozumi Kazuhiko, Date Isao

机构信息

Department of Neurosurgery, The University of Texas Health Science Center at Houston, Houston, TX 77030,

Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.

出版信息

Acta Med Okayama. 2019 Aug;73(4):285-297. doi: 10.18926/AMO/56930.

Abstract

Gliomas are characterized as highly diffuse infiltrating tumors, and currently available treatments such as surgery, radiation and chemotherapy are unfeasible or show limited efficacy against these tumors. Recent genetic and epigenetic analyses of glioma have revealed increasing evidence of the role of driver genetic alterations in glioma development and led to the identification of prognostic factors. Despite these findings, the survival rates of glioma patients remain low, and alternative treatments and novel targets are needed. Recent studies identified neural stem cells as the possible origin of gliomas, and some evidence has revealed shared functions and mechanisms between glioma cells and neurons, also supporting their similarity. The cytoskeleton plays important roles in the migration of normal cells as well as cancer cells. Recent reports have described a role for microtubules, a component of the cytoskeleton, in glioma invasion. Notably, several factors that regulate microtubule functions, such as microtubule-associated proteins, plus-end tracking proteins, or motor proteins, are upregulated in glioma tissues compared with normal tissue, and upregulation of these factors is associated with high invasiveness of glioma cells. In this review, we describe the mechanism of microtubules in glioma invasion and discuss the possibility of microtubule-targeted therapy to inhibit glioma invasion.

摘要

胶质瘤的特征是高度弥漫性浸润性肿瘤,目前可用的治疗方法,如手术、放疗和化疗,对这些肿瘤不可行或疗效有限。最近对胶质瘤的基因和表观遗传学分析揭示了越来越多关于驱动基因改变在胶质瘤发展中作用的证据,并导致了预后因素的识别。尽管有这些发现,胶质瘤患者的生存率仍然很低,因此需要替代治疗方法和新的靶点。最近的研究确定神经干细胞可能是胶质瘤的起源,一些证据表明胶质瘤细胞和神经元之间存在共同的功能和机制,这也支持了它们的相似性。细胞骨架在正常细胞以及癌细胞的迁移中起着重要作用。最近的报道描述了细胞骨架成分微管在胶质瘤侵袭中的作用。值得注意的是,与正常组织相比,胶质瘤组织中一些调节微管功能的因子,如微管相关蛋白、微管正端跟踪蛋白或运动蛋白,上调,这些因子的上调与胶质瘤细胞的高侵袭性相关。在这篇综述中,我们描述了微管在胶质瘤侵袭中的机制,并讨论了微管靶向治疗抑制胶质瘤侵袭的可能性。

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