Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana, USA.
Data Office for Clinical and Translational Research, University of Michigan, Ann Arbor, Michigan, USA.
Sci Rep. 2019 Jul 30;9(1):11040. doi: 10.1038/s41598-019-47309-y.
Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. Many patients are not eligible for curative therapies, such as surgical resection of the tumor or a liver transplant. Transarterial embolization is one therapy clinically used in these cases; however, this requires a long procedure and careful placement of an intraarterial catheter. Gas embolization has been proposed as a fast, easily administered, more spatially selective, and less invasive alternative. Here, we demonstrate the feasibility and efficacy of using acoustic droplet vaporization to noninvasively generate gas emboli within vasculature. Intravital microscopy experiments were performed using the rat cremaster muscle to visually observe the formation of occlusions. Large gas emboli were produced within the vasculature in the rat cremaster, effectively occluding blood flow. Following these experiments, the therapeutic efficacy of gas embolization was investigated in an ectopic xenograft model of hepatocellular carcinoma in mice. The treatment group exhibited a significantly lower final tumor volume (ANOVA, p = 0.008) and growth rate than control groups - tumor growth was completely halted. Additionally, treated tumors exhibited significant necrosis as determined by histological analysis. To our knowledge, this study is the first to demonstrate the therapeutic efficacy of gas embolotherapy in a tumor model.
肝细胞癌是全球癌症相关死亡的第三大主要原因。许多患者不符合治愈性治疗的条件，例如肿瘤的手术切除或肝移植。经动脉栓塞术是这些情况下临床使用的一种治疗方法；然而，这需要一个漫长的过程，并且需要仔细放置动脉内导管。气体栓塞已被提议作为一种快速、易于管理、更具空间选择性和侵入性较小的替代方法。在这里，我们证明了使用声滴蒸发技术非侵入性地在血管内产生气体栓塞的可行性和有效性。使用大鼠提睾肌进行活体显微镜实验，以可视化观察闭塞的形成。在大鼠提睾肌的血管内产生了大的气体栓塞，有效地阻断了血流。在这些实验之后，我们在小鼠的肝细胞癌异位异种移植模型中研究了气体栓塞的治疗效果。治疗组的最终肿瘤体积（ANOVA，p=0.008）和生长速度明显低于对照组-肿瘤生长完全停止。此外，通过组织学分析，治疗后的肿瘤显示出明显的坏死。据我们所知，这项研究首次证明了气体栓塞疗法在肿瘤模型中的治疗效果。
