治疗前的线粒体原始化与对细胞毒性化疗的临床反应相关
Triona Ni Chonghaile1, Kristopher A Sarosiek, Thanh-Trang Vo
1Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
Science (New York, N.Y.)
|October 29, 2011
概括
癌症患者的化疗反应与线粒体原始化有关,这是一种衡量瘤细胞与编程细胞死亡的距离的指标. 高原始瘤对化疗反应更好,这表明这种特性可以指导治疗策略.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 细胞毒性化疗的目标是细胞的基本组成部分,如DNA和微管.
- 瘤细胞被化学疗法选择性地杀死,但控制差异敏感性的精确机制是复杂的.
- 线粒体在亡中的参与在癌细胞死亡中起着至关重要的作用.
研究的目的:
- 为了研究线粒体原始化和对细胞毒性化疗的临床反应之间的相关性.
- 为了确定线粒体原始化是否是各种癌症类型中化疗疗效能的预测生物标志物.
- 探索操纵线粒体原始化的潜力,以提高癌症治疗结果.
主要方法:
- 利用BH3分析量化评估瘤细胞中的线粒体原始化.
- 分析了多发性骨髓瘤,急性骨髓性白血病,淋巴细胞白血病和卵巢癌患者的瘤样本.
- 测量了线粒体对参与细胞死亡信号传递的 BH3 域的反应.
主要成果:
- 化疗的临床反应与瘤细胞中线粒体原始化的治疗前水平有很强的相关性.
- 具有高线粒体启动率的癌症对细胞毒剂表现出优异的反应.
- 耐化学性癌症和正常组织的线粒体原始化水平明显较低.
- 正常组织的原料不良,使它们与敏感的癌细胞区别开来.
结论:
- 线粒体原始化是对细胞毒性化疗敏感性的关键决定因素.
- BH3 分析可以作为预测化疗反应的生物标志物.
- 针对或操纵线粒体原始化是一个潜在的策略,以提高现有的化疗方案的疗效.
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