ULTRASOUND ENHANCEMENT OF CANCER GENE THERAPY

将评估使用超声波加强癌症基因治疗的可能性。初步研究表明，超声波与组织中的气泡相互作用，可以诱导一些避免裂解的细胞摄取大分子，如DNA载体，这些细胞可以存活下来表达基因产物。将这一现象应用于CAN基因治疗，应避免使用病毒载体，允许多个大质粒的转染，重点治疗肿瘤靶点，并将大量肿瘤消融与高效转导存活细胞相结合。另一个有利的考虑是，大多数大型医疗中心已经提供了所需的超声波设备，包括碎石术的冲击波产生系统。三个具体目标是：已经在大多数大型医疗中心提供。三个具体目标是：(1)实验向肿瘤输送DNA质粒和气泡，以优化肿瘤消融和转基因增强过程；(2)在不同的小鼠肿瘤模型上，展示具有既定治疗价值的质粒(如正在开发的用于免疫治疗的质粒)的癌症基因治疗；(3)开发超声增强方案，包括超声引导注射、改变超声参数、通过声空化发射进行治疗监测，以及对肿瘤进行成像，以实现完整的治疗覆盖。最后，该方法将被匹配和定向应用于困难的临床情况，这些情况需要新的方法来成功地管理。这项研究将提供一座桥梁，从基础研究突破到利用这一新技术的具体治疗应用和迫切需要的临床研究计划。

The possibility of using ultrasound to enhance cancer gene therapy will be evaluated. Preliminary research has demonstrated that ultrasound interacting with gas bubbles in tissue can induce some cells which avoid lysis to take up large molecules, such as DNA vectors, and that these cells can survive to express gene products. Application of this phenomenon to can gene therapy should avoid use of viral vectors, allow transfection of multiple large plasmids, focus treatment on the tumor target, and combine massive tumor ablation with high efficiency transfection of survival cells. Another favorable consideration is that needed ultrasound equipment, including shockwave generation systems for lithotripsy, is already available in most large medical centers. Three specific aims are: already available in most large medical centers. Three specific aims are: (1) to experiment with the delivery of DNA plasmids and gas bubbles to tumors for optimizations of the tumor ablation and transfection-enhancement processes, (2) to demonstrate cancer gene therapy with plasmids of established therapeutic value, such as are being developed for immunotherapy, in different mouse tumor models and (3) to develop the ultrasound enhancement protocol including ultrasound guidance of injection, variation of ultrasound parameters, treatment monitoring by acoustic cavitation emissions, and imaging of tumors for complete treatment coverage. Finally, the method will be matched and oriented for application to difficult clinical situations which require new approaches to successful management. This research will provide a bridge from the basic research breakthrough to specific therapeutic applications and urgently needed clinical research programs utilizing this novel technology.