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Oxidative Stress—Part of the Solution or Part of the Problem in the Hypoxic Environment of a Brain Tumor

机译:肿瘤溶解的氧化应激部分或脑肿瘤缺氧环境中的部分问题

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摘要

Rapid growth of brain tumors such as glioblastoma often results in oxygen deprivation and the emergence of hypoxic zones. In consequence, the enrichment of reactive oxygen species occurs, harming nonmalignant cells and leading them toward apoptotic cell death. However, cancer cells survive such exposure and thrive in a hypoxic environment. As the mechanisms responsible for such starkly different outcomes are not sufficiently explained, we aimed to explore what transcriptome rearrangements are used by glioblastoma cells in hypoxic areas. Using metadata analysis of transcriptome in different subregions of the glioblastoma retrieved from the Ivy Glioblastoma Atlas Project, we created the reactive oxygen species-dependent map of the transcriptome. This map was then used for the analysis of differential gene expression in the histologically determined cellular tumors and hypoxic zones. The gene ontology analysis cross-referenced with the clinical data from The Cancer Genome Atlas revealed that the metabolic shift is one of the major prosurvival strategies applied by cancer cells to overcome hypoxia-related cytotoxicity.
机译:脑肿瘤如胶质母细胞瘤的快速生长经常导致缺氧和缺氧区的出现。结果,发生反应性氧物种的富集,损害非血管细胞并引导它们朝向凋亡细胞死亡。然而,癌细胞存活这种暴露并在缺氧环境中茁壮成长。由于不充分解释负责这种持续不同结果的机制,我们旨在探讨缺氧区域中胶质母细胞瘤细胞使用的转录组重排。在从常春藤胶质母细胞瘤的胶质母细胞瘤的不同次区域中使用转录组的元数据分析,我们创造了转录组的反应性氧物种依赖性图。然后将该地图用于分析组织学确定的细胞肿瘤和缺氧区域中的差异基因表达。基因本体分析与来自癌症基因组Atlas的临床资料交叉引用,表明代谢转变是癌细胞克服缺氧相关细胞毒性的主要刺激策略之一。

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