Ji Yanlei, Han Zhen, Shao Limei, Zhao Yuehuan
Department of Special Diagnosis, Shandong Cancer Hospital and Institute China.
Department of Internal Medicine, Jinan Second People's Hospital China.
Int J Clin Exp Pathol. 2015 Sep 1;8(9):9958-74. eCollection 2015.
More and more evidence indicates tumor vasculature plays an important role in tumor radiation response. In this study, we investigated ultrasound stimulated microbubbles to enhance the effects of radiation.
Human bladder cancer HT-1376 xenografts in severe combined immuno-deficient mice were used. High-frequency (25 MHz) ultrasound was used to image tumor responses caused by ultrasound-stimulated microbubbles in combination with radiation. Human bladder xenografts grown in severe combined immunodeficiency (SCID) mice were treated using microbubbles stimulated with ultrasound at 250, 570, or 750 kPa, and exposed to 0, 2, or 8 Gy of radiation. Tumors were imaged prior to treatment and 24 hours after treatment. Spectral analysis of images acquired from treated tumors revealed overall increases in ultrasound backscatter intensity and the spectral intercept parameter.
There existed 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 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.
越来越多的证据表明肿瘤血管系统在肿瘤放射反应中起重要作用。在本研究中，我们研究了超声刺激微泡以增强放射效果。
使用严重联合免疫缺陷小鼠体内的人膀胱癌HT - 1376异种移植瘤。采用高频（25 MHz）超声对超声刺激微泡联合放射引起的肿瘤反应进行成像。对在严重联合免疫缺陷（SCID）小鼠体内生长的人膀胱异种移植瘤，使用250、570或750 kPa超声刺激的微泡进行处理，并给予0、2或8 Gy的放射剂量。在治疗前和治疗后24小时对肿瘤进行成像。对处理后肿瘤获取图像的频谱分析显示超声背向散射强度和频谱截距参数总体增加。
超声刺激微泡血管扰动与放射的单次联合治疗在体内存在协同效应，联合治疗诱导的细胞杀伤比单独治疗大10倍以上。我们进一步证明，诱导神经酰胺相关的内皮细胞凋亡导致血管破坏是一种致病机制。超声和微泡的体内实验允许在效果相当的情况下显著降低放射剂量。
我们设想这种独特的基于超声的血管扰动与放射联合治疗方法可用于增强肿瘤放射效果，从而实现更大程度的肿瘤根除。
