Heller L C, Coppola D
Center for Molecular Delivery, c/o Department of Surgery MDC16, University of South Florida, 12901 Bruce B Downs Boulevard, Tampa, FL 33612, USA.
Gene Ther. 2002 Oct;9(19):1321-5. doi: 10.1038/sj.gt.3301802.
In vivo electroporation is an efficient means of increasing plasmid DNA delivery to normal tissues, such as skin and muscle, as well as directly to tumors. In the experiments described here, plasmid DNA was delivered by in vivo electroporation to B16 mouse melanomas using two very different pulsing protocols. Reporter expression increased 21- or 42-fold, respectively with electroporation over injection alone. The growth of experimental melanomas with an approximate diameter of 4 mm on the day of treatment was monitored after electroporation delivery of reporter plasmid DNA. Remarkably, short-term complete regressions using one of these pulsing protocols occurred in up to 100% of mice. These regressions continued long term in up to 83% of animals. 70% of these mice were resistant to challenge with B16 melanoma cells. Histological analysis revealed large numbers of apoptotic cells 24 h after treatment. This antitumor effect did not require therapeutic cDNA expression or eukaryotic sequences.
体内电穿孔是一种提高质粒DNA导入正常组织（如皮肤和肌肉）以及直接导入肿瘤的有效方法。在此处描述的实验中，使用两种截然不同的脉冲方案，通过体内电穿孔将质粒DNA导入B16小鼠黑色素瘤。与单独注射相比，电穿孔后报告基因表达分别增加了21倍或42倍。在报告质粒DNA经电穿孔导入后，对治疗当天直径约4 mm的实验性黑色素瘤的生长情况进行了监测。值得注意的是，使用其中一种脉冲方案，高达100%的小鼠出现了短期完全消退。高达83%的动物长期维持这种消退状态。这些小鼠中有70%对B16黑色素瘤细胞的攻击具有抗性。组织学分析显示，治疗后24小时有大量凋亡细胞。这种抗肿瘤作用不需要治疗性cDNA表达或真核序列。
