Xie Xiaoming, Xia Weiya, Li Zhongkui, Kuo Hsu-Ping, Liu Yuanfang, Li Zheng, Ding Qingqing, Zhang Su, Spohn Bill, Yang Yan, Wei Yongkun, Lang Jing-Yu, Evans Douglas B, Chiao Paul J, Abbruzzese James L, Hung Mien-Chie
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer Cell. 2007 Jul;12(1):52-65. doi: 10.1016/j.ccr.2007.05.009.
Pancreatic cancer is an aggressive malignancy with morbidity rates almost equal to mortality rates because of the current lack of effective treatment options. Here, we describe a targeted approach to treating pancreatic cancer with effective therapeutic efficacy and safety in noninvasive imaging models. We developed a versatile expression vector "VISA" (VP16-GAL4-WPRE integrated systemic amplifier) and a CCKAR (cholecystokinin type A receptor) gene-based, pancreatic-cancer-specific promoter VISA (CCKAR-VISA) composite to target transgene expression in pancreatic tumors in vivo. Targeted expression of BikDD, a potent proapoptotic gene driven by CCKAR-VISA, exhibited significant antitumor effects on pancreatic cancer and prolonged survival in multiple xenograft and syngeneic orthotopic mouse models of pancreatic tumors with virtually no toxicity.
胰腺癌是一种侵袭性恶性肿瘤,由于目前缺乏有效的治疗方法,其发病率几乎与死亡率相当。在此,我们描述了一种在非侵入性成像模型中治疗胰腺癌的靶向方法,该方法具有有效的治疗效果和安全性。我们开发了一种多功能表达载体“VISA”(VP16-GAL4-WPRE整合系统放大器)和一种基于CCKAR(胆囊收缩素A受体)基因的胰腺癌特异性启动子VISA(CCKAR-VISA)复合物,以在体内靶向胰腺肿瘤中的转基因表达。由CCKAR-VISA驱动的强效促凋亡基因BikDD的靶向表达,在多种胰腺癌异种移植和同基因原位小鼠模型中对胰腺癌表现出显著的抗肿瘤作用,并延长了生存期,且几乎没有毒性。