Microbubble-assisted p53, RB, and p130 gene transfer in combination with radiation therapy in prostate cancer.
Microbubble-assisted p53, RB, and p130 gene transfer in combination with radiation therapy in prostate cancer.
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DOI：
10.2174/1566523211313030001
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发表时间：
2013-05
影响因子：
3.6
通讯作者：
R. Nande;A. Greco;M. Gossman;Jeffrey P. Lopez;L. Claudio;M. Salvatore;A. Brunetti;J. Denvir;C. Howard;P. Claudio
中科院分区：
文献类型：
--
作者：
R. Nande;A. Greco;M. Gossman;Jeffrey P. Lopez;L. Claudio;M. Salvatore;A. Brunetti;J. Denvir;C. Howard;P. Claudio
结合放射治疗和腺病毒载体的直接瘤内（IT）注射已被探索作为一种手段，以提高基因转移的治疗潜力。基因转移的主要挑战是将核酸直接全身递送到受影响的组织中。超声（US）造影剂（微泡）是增强全身给药基因靶向递送的可行候选物。在这里，我们表明，p53，pRB和p130基因转移介导的超声空化微泡在肿瘤部位导致靶向基因转导和增加减少肿瘤生长相比，DU-145前列腺癌细胞异种移植瘤内治疗腺病毒（Ad）或单独放射。与Ad.p130处理的肿瘤相比，微泡辅助/US介导的Ad.p53和Ad.RB处理的肿瘤显示肿瘤体积显著减小（p<0.05）。此外，与单独的辐射相比，与外部束辐射组合的p53和RB的US介导的微泡递送导致DU-145异种移植裸鼠中最显著的肿瘤减少（p<0.05）。这些发现突出了这种新型图像引导基因转移技术与外部光束辐射相结合对患有治疗抵抗性疾病的前列腺癌患者的潜在治疗应用。
Combining radiation therapy and direct intratumoral (IT) injection of adenoviral vectors has been explored as a means to enhance the therapeutic potential of gene transfer. A major challenge for gene transfer is systemic delivery of nucleic acids directly into an affected tissue. Ultrasound (US) contrast agents (microbubbles) are viable candidates to enhance targeted delivery of systemically administered genes. Here we show that p53, pRB, and p130 gene transfer mediated by US cavitation of microbubbles at the tumor site resulted in targeted gene transduction and increased reduction in tumor growth compared to DU-145 prostate cancer cell xenografts treated intratumorally with adenovirus (Ad) or radiation alone. Microbubble-assisted/US-mediated Ad.p53 and Ad.RB treated tumors showed significant reduction in tumor volume compared to Ad.p130 treated tumors (p<0.05). Additionally, US mediated microbubble delivery of p53 and RB combined with external beam radiation resulted in the most profound tumor reduction in DU-145 xenografted nude mice (p<0.05) compared to radiation alone. These findings highlight the potential therapeutic applications of this novel image-guided gene transfer technology in combination with external beam radiation for prostate cancer patients with therapy resistant disease.