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在消化道瘤的生长中,对 Hedgehog 连接体刺激的广泛需求
David M Berman1, Sunil S Karhadkar, Anirban Maitra
1Department of Molecular Biology and Genetics and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Nature
|October 2, 2003
概括
刺 (Hh) 信号通路驱动许多消化道癌症的生长,与戈林综合征不同. 用像环胺这样的抗剂准这种途径显示出治疗这些致命恶性瘤的前景.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症信号传递 癌症信号传递
背景情况:
- 刺 (Hh) 信号通路与各种组织的瘤发生有关.
- 戈林综合征和零星突变激活Hh信号,导致特定的癌症.
研究的目的:
- 为了研究Hh通路活性在消化道瘤中的作用.
- 确定这些癌症中Hh通路激活的机制.
- 评估Hh通路抑制的治疗潜力.
主要方法:
- 在多种消化道瘤样本中分析Hh通路活性.
- 在体外和体内用环胺 (Hh通路抗剂) 治疗.
- 检测Hh连接体转录 (索尼克刺,印度刺).
- 评估Hh-中和抗体和外源的Hh联体效应.
主要成果:
- 在食道,胃,胆道和胰腺瘤中观察到Hh通路活性增加,但没有结肠癌.
- 环胺在体外抑制了瘤细胞的生长,并在体内减少了异种移植的瘤大小.
- 在这些消化系统癌症中,Hh通路的激活是由内源的Hh联体表达驱动的,而不是突变.
- 通过转录分析和功能检测证实了HH联体表达.
结论:
- 刺信号通路是常见的消化道恶性瘤的一个重要子集的增长的关键驱动力.
- 与戈林综合征中观察到的突变不同,Hh通路的依赖联体激活是这些癌症的关键.
- 使用像环胺这样的药物来抑制Hh通路,代表了这些致命癌症的潜在治疗策略.
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