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阐明调控高级别浆液性卵巢癌中癌症干细胞和非干细胞的基因调控网络。

Elucidating the gene regulatory networks modulating cancer stem cells and non-stem cancer cells in high grade serous ovarian cancer.

机构信息

Bioinformatics Centre, Bose Institute, Kolkata 700054, India.

Bioinformatics Centre, Bose Institute, Kolkata 700054, India.

出版信息

Genomics. 2019 Jan;111(1):103-113. doi: 10.1016/j.ygeno.2018.01.006. Epub 2018 Feb 6.

Abstract

The origin and pathogenesis of epithelial ovarian cancer have perplexed investigators for decades. The most prevalent type of it is the high-grade serous ovarian carcinoma (HGSOv) which is a highly aggressive disease with high relapse rates and insurgence of chemo-resistance at later stages of treatment. These are driven by a rare population of stem cell like cancer cells called cancer stem cells (CSCs). We have taken up a systems approach to find out the common gene interaction paths between non-CSC tumor cells (CCs) and CSCs in HGSOv. Detailed investigation reveals a set of 17 Transcription Factors (named as pivot-TFs) which can govern changes in the mode of gene regulation along these paths. Overall, this work highlights a divergent road map of functional information relayed by these common key players in the two cell states, which might aid towards designing novel therapeutic measures to target the CSCs for ovarian cancer therapy.

摘要

几十年来,上皮性卵巢癌的起源和发病机制一直困扰着研究人员。最常见的类型是高级别浆液性卵巢癌(HGSOv),这是一种高度侵袭性疾病,复发率高,在治疗后期出现化疗耐药。这些是由一种称为癌症干细胞(CSC)的罕见干细胞样癌细胞驱动的。我们采用系统方法来找出 HGSOv 中非 CSC 肿瘤细胞(CCs)和 CSCs 之间常见的基因相互作用途径。详细研究揭示了一组 17 种转录因子(称为枢轴-TFs),它们可以控制这些途径中基因调控模式的变化。总的来说,这项工作强调了这些共同关键因子在两种细胞状态下传递功能信息的不同路线图,这可能有助于设计针对卵巢癌治疗的 CSC 的新型治疗措施。

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