瘤对放射治疗的反应由内皮细胞亡调节
Monica Garcia-Barros1, Francois Paris, Carlos Cordon-Cardo
1Laboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
概括
瘤对放射治疗的反应取决于癌细胞类型和血管敏感度. 瘤血管中的受损内皮细胞亡导致辐射抵抗,突出显示微血管损伤是癌症治疗结果的关键因素.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 辐射瘤学 辐射瘤学
背景情况:
- 放射治疗是一种常见的癌症治疗方法,约有50%的患者受到影响.
- 瘤对辐射的反应受瘤细胞特征和瘤微环境的影响.
- 微血管敏感性在辐射反应中的作用需要进一步研究.
研究的目的:
- 为了调查瘤对放射治疗的反应是由微血管敏感性决定的假设.
- 探索内皮细胞亡对瘤生长和辐射耐药性的影响.
- 为了确定微血管损伤是否影响瘤细胞对临床相关辐射剂量的反应.
主要方法:
- 在转基因小鼠中利用了MCA/129纤维沙尔科马和B16F1黑色素瘤.
- 对比瘤生长和微血管内皮细胞亡在抗亡的小鼠 (酸胺基酶缺乏或巴克斯缺乏) 与野生型小鼠.
- 评估瘤对高达20灰度 (Gy) 的单剂量辐射的反应.
主要成果:
- 在耐亡的小鼠中生长的瘤显著减少了基线微血管内皮亡.
- 这些瘤的生长速度比野生类型小鼠的瘤快200-400%.
- 抗亡的小鼠中的瘤在照射后表现出减少的内皮细胞亡,并且对高达20 Gy的辐射剂量具有抗性.
- 野生型小鼠的瘤对辐射显示出敏感性.
结论:
- 内皮细胞亡作为调节血管新生依赖瘤生长的恒温因子.
- 微血管敏感性,特别是内皮细胞亡,是瘤对放射治疗反应的关键决定因素.
- 向微血管损伤可能是提高放射治疗在癌症治疗中的疗效的策略.
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