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缺氧是胶质母细胞瘤的驱动因素,可能成为胶质母细胞瘤治疗的新工具。

Hypoxia Is the Driving Force Behind GBM and Could Be a New Tool in GBM Treatment.

作者信息

Kalkan Rasime

机构信息

Department of Medical Genetics, Faculty of Medicine, Near East University, Post Code: 99138, Turkish Republic of Northern Cyprus.

出版信息

Crit Rev Eukaryot Gene Expr. 2015;25(4):363-9. doi: 10.1615/critreveukaryotgeneexpr.2015015601.

Abstract

Glioblastoma (GBM) can be divided into two distinct disease entities according to the genetic and the epigenetic background of the tumor. Tumor location is associated with high variability in its genetic abnormalities. The treatment procedures for these tumors are often unsuccessful because of the cellular heterogeneity and intrinsic ability of the tumor cells to invade healthy tissues. The fatal outcomes of these tumors have encouraged researchers to find new markers associated with prognosis and treatment planning. In the present communication, we discuss hypoxia as a new therapeutic target of glioblastoma multiforme and the molecular and phenotypic effects of hypoxia on cancer cells. We focus on the inhibition of the signaling pathways, which is associated with the hypoxia-mediated maintenance of glioblastoma stem cells and the knockdown of the hypoxia-inducible factor 1-alpha (HIFlα). This discussion may contribute to the development of new specifically targeted treatments. Furthermore, we highlight the idea that hypoxia-inducible factors (HIFs) could be attractive molecular targets for GBM therapeutics.

摘要

根据肿瘤的基因和表观遗传背景,胶质母细胞瘤(GBM)可分为两种不同的疾病实体。肿瘤位置与其基因异常的高度变异性相关。由于肿瘤细胞的细胞异质性和侵入健康组织的内在能力,这些肿瘤的治疗程序往往不成功。这些肿瘤的致命后果促使研究人员寻找与预后和治疗计划相关的新标志物。在本通讯中,我们讨论缺氧作为多形性胶质母细胞瘤的新治疗靶点以及缺氧对癌细胞的分子和表型影响。我们专注于抑制与缺氧介导的胶质母细胞瘤干细胞维持相关的信号通路以及缺氧诱导因子1-α(HIFlα)的敲低。这一讨论可能有助于开发新的特异性靶向治疗方法。此外,我们强调缺氧诱导因子(HIFs)可能是GBM治疗有吸引力的分子靶点这一观点。

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