在患者衍生的肺组织中FLASH辐射的缓解效应
Maxime Dubail1, Chloé Lafouasse2, Sophie Heinrich1
1Institut Curie, Inserm U1021-CNRS UMR 3347, University Paris-Saclay, PSL Research University, Centre Universitaire, 91405 Orsay Cedex, France.
闪光辐射疗法可以避免人类肺组织受到辐射损伤,在患者获得的肺部切片中显示细胞增殖增加和DNA损伤标志物减少. 这表明FLASH疗法.
科学领域:
- 在瘤学瘤学.
- 辐射瘤学 辐射瘤学
- 细胞生物学 细胞生物学
背景情况:
- 治疗癌症的辐射疗法可能会导致严重的副作用,如肺炎和纤维化,影响患者的生活质量.
- 闪光辐射疗法是一种新的技术,可以以超快的剂量率输送辐射,有望减少对健康组织的毒性,同时保持抗瘤功效.
- 有益的"FLASH效应"已在临床前模型中观察到,但尚未在人体组织中观察到.
研究的目的:
- 调查FLASH辐射是否可以诱导对人类健康的肺组织产生保护作用.
- 评估FLASH辐射对人类肺部实验体细胞增殖和分子通路的影响.
主要方法:
- 人类精确切割肺切片 (Hu-PCLS) 来自19名肺癌患者,这些患者接受了分管切除术.
- 使用9 Gy的电子FLASH装置对Hu-PCLS进行了ex vivo辐射,比较了传统模式和FLASH模式.
- 监测细胞分裂,并进行RNA测序 (RNAseq) 来分析机械反应.
主要成果:
- 与治疗后24小时的传统照射相比,FLASH照射导致Hu-PCLS中分裂细胞的比例更高.
- RNAseq分析显示,细胞周期检查点抑制减弱,减少p53亲细胞亡基因表达,减少DNA损伤和抗氧化剂通路激活与FLASH辐射.
- 这些分子变化表明,在用FLASH放射治疗的肺组织中,反应不那么有害.
结论:
- 细胞增殖是患者获得的样本中正常肺部对FLASH辐射反应的早期指标.
- 这些发现证明了FLASH放射治疗在挽救人类肺组织方面的潜力,支持其未来的临床应用.
- 这项研究为FLASH放射治疗在肺癌治疗中的临床转化提供了关键证据.
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