PNAS：超声波激活的微泡可能增强肿瘤放疗的效果

一项刊登在PNAS上的研究发现，一种基于超声波的疗法能让小鼠的肿瘤对放射性治疗敏感。辐射主要通过破坏DNA以及——根据近来的证据——通过破坏肿瘤的血管从而摧毁肿瘤。Gregory Czarnota及其同事研究了一种已知能扰动血管的疗法——超声波调控的微泡激发。

这种微泡是微米直径的化学惰性气体球——是否能够增强辐射的肿瘤破坏效应。这组作者向有肿瘤的小鼠静脉注射了微泡，然后让这个区域接触让微泡破裂的超声波频率。其中一些肿瘤在这之后接触了电离辐射。这种组合治疗造成的肿瘤细胞死亡数比单独使用放疗要多出大约10倍。

相对于只使用放疗，用这种组合疗法重复治疗能增加存活时间并延迟肿瘤的生长。组织分析表明这种组合疗法引发了肿瘤血管内壁的程序性细胞死亡，减少了血流并引发了肿瘤细胞死亡。这组作者说，这些发现提示放疗加以超声波激活的微泡可能增加癌症疗法的功效并且可能减少放疗所需的总剂量。

doi:10.1073/pnas.1200053109
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Tumor radiation response enhancement by acoustical stimulation of the vasculature

Gregory J. Czarnotaa,b,c,d,1, Raffi Karshafianc,d,e, Peter N. Burnsc,d, Shun Wonga,b,d, Azza Al Mahroukia,c, Justin W. Leea,b,c,d, Amanda Caissiea,c, William Trana, Christina Kima,c,d, Melissa Furukawaa,c, Emily Wonga,c, and Anoja Gilesa,c

We have discovered that ultrasound-mediated microbubble vascular disruption can enhance tumor responses to radiation in vivo. We demonstrate this effect using a human PC3 prostate cancer xenograft model. Results indicate a synergistic effect in vivo with combined single treatments of ultrasound-stimulated microbubble vascular perturbation and radiation inducing an over 10-fold greater cell kill with combined treatments. We further demonstrate with experiments in vivo that induction of ceramide-related endothelial cell apoptosis, leading to vascular disruption, is a causative mechanism. In vivo experiments with ultrasound and bubbles permit radiation doses to be decreased significantly for comparable effect. We envisage this unique combined ultrasound-based vascular perturbation and radiation treatment method being used to enhance the effects of radiation in a tumor, leading to greater tumor eradication.