Institut de Recherche Thérapeutique de l'Université de Nantes, CRCNA INSERM UMR892 /Université de Nantes, Nantes Cedex 1, France.
Curr Mol Pharmacol. 2009 Nov;2(3):263-84. doi: 10.2174/1874467210902030263.
Glioblastoma Multiforme (GBM) tumors are the most common type of brain tumors. These tumors are in general very malignant and can be characterized as rapidly progressive astrocytomas. The pathological characteristics of these tumors are exemplified by an active invasiveness, necrosis and a specialized form of angiogenesis, known as microvascular hyperplasia. These pathological features are thought to be due to tissue hypoxia. Cells that are under hypoxic stress can either develop an adaptive response that includes increasing the rate of glycolysis and angiogenesis or undergo cell death by promoting apoptosis and/or necrosis. The ability of tumor cells to maintain a balance between an adaptation to hypoxia and cell death is regulated by a family of transcription factors called hypoxia-inducing factors (HIF), which are essential for the regulation of the expression of a large number of hypoxia-responsive genes. The hypothesis that tumor hypoxia would facilitate the likelihood of metastases, tumor recurrence, resistance to chemotherapy and radiotherapy and the invasive potential; all of which culminate in a decrease in patient survival. In this review we will summarize the role of hypoxia in GBM with regard to drug therapy and toxicity and attempt to describe the possible interactions between hypoxia and apoptosis.
多形性胶质母细胞瘤（GBM）肿瘤是最常见的脑肿瘤类型。这些肿瘤通常非常恶性，可以被特征化为快速进展的星形细胞瘤。这些肿瘤的病理特征表现为活跃的侵袭性、坏死和一种特殊形式的血管生成，称为微血管增生。这些病理特征被认为是由于组织缺氧引起的。处于缺氧应激下的细胞要么通过增加糖酵解和血管生成的速度来发展适应性反应，要么通过促进细胞凋亡和/或坏死来发生细胞死亡。肿瘤细胞在适应缺氧和细胞死亡之间保持平衡的能力是由一组称为缺氧诱导因子（HIF）的转录因子调节的，HIF 对于调节大量缺氧反应基因的表达是必不可少的。肿瘤缺氧会增加转移、肿瘤复发、对化疗和放疗的抵抗力以及侵袭性的可能性的假说；所有这些都导致患者生存率下降。在这篇综述中，我们将总结缺氧在 GBM 药物治疗和毒性方面的作用，并尝试描述缺氧与细胞凋亡之间的可能相互作用。
