在患者衍生的结肠直肠癌模型中的染色质重塑
Kun Xiang1, Ergang Wang1, John Mantyh2
1Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, 27708, USA.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|February 21, 2024
概括
患者衍生癌症模型,如有机体和异种移植,显示出明显的细胞进化. 微环境显著影响染色质重塑,影响瘤生长和药物敏感性,对于临床结果预测至关重要.
科学领域:
- 癌症生物学 癌症生物学
- 基因组学就是基因组学.
- 翻译医学是一种翻译医学.
背景情况:
- 来自患者的模型 (器官体和外来移植) 对癌症研究至关重要.
- 在这些模型中,了解细胞进化和药物反应至关重要.
研究的目的:
- 在匹配的结直肠癌患者瘤和衍生模型中比较转录组和染色质可访问性.
- 研究微环境对细胞适应和药物敏感性的影响.
主要方法:
- 患者瘤,有机体,外移植和有机体衍生外移植的转录和染色质可访问性概况.
- 生物信息分析以确定重塑轴和转录因子结合.
- 基因沉默实验和药物敏感性测试.
主要成果:
- 确定了两个主要的染色质重塑轴,将患者瘤与模型区分开来,将异种移植与器官区分开来.
- PDOX模型与PDX的相似性更大,突出了增长环境的作用.
- 确定KLF14和EGR2是影响瘤生长和药物敏感性的关键转录因子.
结论:
- 结肠直肠癌细胞在有机体和异种移植中经历了明显的微环境驱动的染色质重塑.
- 这些适应影响瘤生长和药物敏感性,影响患者衍生模型的预测价值.
- 考虑微环境影响对于解释癌症模型的结果至关重要.
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