Basic study for sonodynamic therapy to the experimental brain tumor

我们证实了声动力疗法对实验性大鼠脑瘤的疗效。将C6胶质瘤细胞移植到Wistcr大鼠脑内，用聚焦超声和孟加拉红作为光敏剂，评价声动力学治疗的效果。采用聚焦功率为25W/cm~2，频率为1 MHz，作用时间为5min的聚焦超声和孟加拉玫瑰，在体外以C6大鼠胶质瘤细胞、U251和U105人脑胶质瘤细胞为研究对象，以光敏剂为光敏剂的平行超声声动力学治疗效果进行了评价。证实了低强度超声对恶性胶质瘤细胞的杀伤作用，并与部分由细胞表面LRP/α-2-MR转运的光敏剂光敏剂联合应用可增强抗肿瘤活性。EN…胞浆大量吞噬和胞膜中断观察到更多的内皮细胞，这表明超声动力疗法破坏了肿瘤周围脑组织的血脑屏障。在这项实验中，人类胶质瘤细胞U251和U105对声动力疗法的敏感性不同，U251胶质瘤细胞在裸鼠脑内存活，但没有生长到肿块。根据每种动物的不同，这些细胞的增殖情况可能不同。U105胶质瘤细胞既不能在裸鼠脑内存活，也不能生长到块状，不能作为实验性脑肿瘤模型。我们用U87人脑胶质瘤细胞进行裸鼠实验性脑肿瘤的实验研究。这些细胞被成功地移植到裸鼠大脑中，并在一周内生长到块状，即U87人。使用聚焦超声对脑胶质瘤细胞进行声动力学治疗。暴露裸鼠脑，消毒后用聚焦超声照射，1周后超声照射组肿瘤最大径与对照组比较，前者平均40 mm，后者平均38 mm，说明该模型不能达到声动力治疗的效果。我们推测C6胶质瘤细胞与人脑胶质瘤细胞U251、U105和U87的增殖活性和/或光敏剂对这些胶质瘤细胞的累积速率有差异。较少

We confirmed efficacy of sonodynamic therapy to the experimental brain tumor in the rat. C6 glioma cells were implanted in the brain of Wistcr rat and evaluated efficacy of sonodynamic therapy using a focused ultrasound and Rose Bengal as photosensitizer. A selective anti-tumor effect against cerebral gloma while sparing normal brain tissues was achieved by sonodynamic focused therapy consisting of focused ultrasound at 25 W/cm2 at 1 MHz for 5 min and Rose Bengal, In vitro, C6 rat glioma cells and U251 and U105 human glioma cells were used and evaluated in the efficacy of sonodynamic therapy using parallel ultrasound with photofrin as a photosensitizer Usefulness of low-intensity ultrasound for the cell killing of malignant glioma was confirmed and anti-tumor activity might be enhanced by combination with photofrin, which partially transported by cell surface LRP/ α 2-MR In EM study, swelling of the cytoplasm, plenty of pinocytosis and interruption of the cytoplasmic membrane of the en … More dothelial cells were observed, suggesting-destruction of the blood brain barrier-of the-peritumoral-brain tissue by the sonodynamic therapy. In this experiment, human glioma cells, U251-and U105, differed in sensitivity to the sonodynamic therapy U251 glioma cells survived in the nude rat brain but didn't grow up to neoplastic mass. These cells might differ in proliferation individually, depending upon each animal. U105 glioma cells neither survived in the nude rat brain nor grew up to the mass, so these glioma cells couldn't be used as experimental brain tumor model. We used U87 human glioma cells for experimental brain tumor in the nude rat. These cells were implanted into the nude rat brain-successfully and grew up-to the mass in a week, so U87 human. glioma cells were used for sonodynamic-therapy using the-focused ultrasound. The nude rat brain was exposed and was irradiated by the focused ultrasound after disinfection, A week later, the tumor maximum diameter was compared ultrasound group with control group, 40 mm in average in the former and 38 mm in the latter, therefore, effectiveness of sonodynamic therapy could not be obtained in this model. We speculated that there were any differences of proliferation activity between C6 glioma cells and human glioma cells of U251, U105 and U87 and /or of accumulation rate of photosensitizer to these glioma cells. Less