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神经胶质瘤的发生机制和神经干细胞在脑肿瘤治疗中的应用。

Gliomagenesis and the use of neural stem cells in brain tumor treatment.

机构信息

Department of Neurosurgery, Johns Hopkins University, School of Medicine, CRB II, Room 272, 1550 Orleans Street, Baltimore, MD 21231, USA.

出版信息

Anticancer Agents Med Chem. 2010 Feb;10(2):121-30. doi: 10.2174/187152010790909290.

Abstract

The role of neural stem cells (NSCs) in both the physiological and pathological processes in the brain has been refined through recent studies within the neuro-oncological field. Alterations in NSC regulatory mechanisms may be fundamental for the development and progression of malignant gliomas. A subpopulation of cells within the tumor known as brain tumor stem cells (BTSCs) have been shown to share key properties with NSCs. The BTSC hypothesis has significantly contributed to a potential understanding as to why brain tumors hold such dismal prognosis. On the other hand, the normal NSCs possess the capacity to migrate extensively towards the tumor bulk as well as to lingering neoplastic regions of the brain. The tropism of NSCs towards brain tumors may provide an additional tool for the treatment of brain cancer. The creation of potential therapies through the use of NSCs has been studied and includes the delivery of gene products to specific locations of the central nervous system selectively targeting malignant brain tumor cells and maximizing the efficiency of their delivery. Here, the proposed mechanisms of how brain tumors emerge, the molecular pathways interrupted in NSC pathogenesis and the most recent preclinical results in the use of NSCs for glioma treatment are reviewed.

摘要

神经干细胞(NSCs)在大脑的生理和病理过程中的作用,通过神经肿瘤学领域的最近研究得到了完善。NSC 调节机制的改变可能是恶性神经胶质瘤发生和发展的基础。肿瘤内称为脑肿瘤干细胞(BTSC)的细胞亚群已被证明与 NSCs 具有关键特性。BTSC 假说极大地促进了对为什么脑肿瘤预后如此差的潜在理解。另一方面,正常 NSCs 具有向肿瘤实质以及大脑中残留的肿瘤区域广泛迁移的能力。NSCs 对脑肿瘤的趋向性可能为脑癌治疗提供另一种工具。通过使用 NSCs 来创建潜在的治疗方法已经进行了研究,包括将基因产物递送到中枢神经系统的特定位置,选择性地靶向恶性脑肿瘤细胞,并最大限度地提高其递药效率。在这里,我们回顾了脑肿瘤是如何产生的、NSC 发病机制中被阻断的分子途径以及最近在使用 NSCs 治疗神经胶质瘤方面的临床前研究结果。

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