Author/Authors :
Xie، نويسنده , , Xiaoming and Xia، نويسنده , , Weiya and Li، نويسنده , , Zhongkui and Kuo، نويسنده , , Hsu-Ping and Liu، نويسنده , , Yuanfang and Li، نويسنده , , Zheng-Rong Ding، نويسنده , , Qingqing and Zhang، نويسنده , , Su and Spohn، نويسنده , , Bill Z. Yang، نويسنده , , Yan and Wei، نويسنده , , Yongkun and Lang، نويسنده , , Jing-Yu and Evans، نويسنده , , Douglas B. and Chiao، نويسنده , , Paul J. and Abbruzzese، نويسنده , , James L. and Hung، نويسنده , , Mien-Chie، نويسنده ,
Abstract :
Summary
atic 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.
