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肿瘤的疗效。将C6胶质瘤细胞植入Wistcr大鼠脑内，以聚焦超声和玫瑰为光敏剂评价声动力治疗的效果。在保留正常脑组织的情况下，通过聚焦超声（25 W/cm2, 1 MHz, 5 min）和Rose Bengal的声动力聚焦治疗，实现了对脑胶瘤的选择性抗肿瘤作用。以C6大鼠胶质瘤细胞和U251、U105人胶质瘤细胞作为光敏剂，采用平行超声对其声动力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，与光frin联合可增强其抗肿瘤活性，光frin部分通过细胞表面LRP/ α 2-MR转运。大量的胞饮和细胞质膜的破坏，更多的内皮细胞被观察到，提示声动力治疗破坏了肿瘤周围脑组织的血脑屏障。在本实验中，人胶质瘤细胞U251-和U105对声动力治疗的敏感性不同。U251胶质瘤细胞在裸大鼠脑中存活，但没有长成肿瘤块。这些细胞的增殖可能因动物的不同而不同。U105胶质瘤细胞既不能在裸大鼠脑内存活，也不能长成肿块，因此不能作为实验性脑肿瘤模型。我们用U87人胶质瘤细胞进行裸鼠脑瘤实验。这些细胞被成功地植入裸鼠大脑，并在一周内长成了大量的细胞，因此U87人。胶质瘤细胞使用聚焦超声进行声动力治疗。裸鼠脑暴露消毒后用聚焦超声照射，1周后超声组与对照组比较肿瘤最大直径，超声组平均40 mm，对照组平均38 mm，因此在该模型中无法获得声动力治疗的效果。我们推测C6胶质瘤细胞与人U251、U105和U87胶质瘤细胞的增殖活性和/或光敏剂对这些胶质瘤细胞的积累速率存在差异。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