title: Targeted expression of BikDD eradicates pancreatic tumors in noninvasive imaging models.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xie
authors.forename: Weiya
authors.initials: W
authors.lastname: Xia
authors.forename: Zhongkui
authors.initials: Z
authors.lastname: Li
authors.forename: Hsu-Ping
authors.initials: HP
authors.lastname: Kuo
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Liu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Ding
authors.forename: Su
authors.initials: S
authors.lastname: Zhang
authors.forename: Bill
authors.initials: B
authors.lastname: Spohn
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Yongkun
authors.initials: Y
authors.lastname: Wei
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Lang
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Evans
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Chiao
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
mesh_terms: D000818:Animals; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010190:Pancreatic Neoplasms / Q000235:genetics*; D011949:Receptors, Cholecystokinin / Q000235:genetics; D019076:Transgenes
chemical_list: D011949:Receptors, Cholecystokinin