Targeted Expression of BikDD Eradicates Pancreatic Tumors in Noninvasive Imaging Models

Xiaoming Xie; Weiya Xia; Zhongkui Li; Hsu Ping Kuo; Yuanfang Liu; Zheng Li; Qingqing Ding; Su Zhang; Bill Spohn; Yan Yang; Yongkun Wei; Jing Yu Lang; Douglas B. Evans; Paul J. Chiao; James L. Abbruzzese; Mien Chie Hung

doi:10.1016/j.ccr.2007.05.009

Targeted Expression of BikDD Eradicates Pancreatic Tumors in Noninvasive Imaging Models

Xiaoming Xie
, Weiya Xia
, Zhongkui Li
, Hsu Ping Kuo
, Yuanfang Liu
, Zheng Li
, Qingqing Ding
, Su Zhang
, Bill Spohn
, Yan Yang
, Yongkun Wei
, Jing Yu Lang
, Douglas B. Evans
, Paul J. Chiao
, James L. Abbruzzese
, Mien Chie Hung

Research output: Contribution to journal › Article › peer-review

73 Scopus citations

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.

Original language	English (US)
Pages (from-to)	52-65
Number of pages	14
Journal	Cancer cell
Volume	12
Issue number	1
DOIs	https://doi.org/10.1016/j.ccr.2007.05.009
State	Published - Jul 10 2007

Keywords

CELLCYCLE

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

MD Anderson CCSG core facilities

Research Animal Support Facility

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10.1016/j.ccr.2007.05.009

Cite this

@article{1c64247666b34543a602a107ea135582,

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.",

keywords = "CELLCYCLE",

author = "Xiaoming Xie and Weiya Xia and Zhongkui Li and Kuo, \{Hsu Ping\} and Yuanfang Liu and Zheng Li and Qingqing Ding and Su Zhang and Bill Spohn and Yan Yang and Yongkun Wei and Lang, \{Jing Yu\} and Evans, \{Douglas B.\} and Chiao, \{Paul J.\} and Abbruzzese, \{James L.\} and Hung, \{Mien Chie\}",

note = "Funding Information: We thank Dr. Michael Carey (University of California Los Angeles School of Medicine, Los Angeles, CA) for providing the pGL3-TSTA-Luc vector; Dr. James B. Uney (University of Bristol, Bristol, United Kingdom) for providing the pGEM-3Z-WPRE vector; the biochemistry laboratory in the Department of Veterinary Medicine and Surgery for measuring serum AST, ALT, and BUN; and the Department of Scientific Publications at M.D. Anderson Cancer Center for editing this manuscript. This work was supported by an NIH SPORE grant in Pancreatic Cancer (P20 CA101936), a grant from Topfer Funds (M.-C.H. and J.L.A.), M.D. Anderson Cancer Center Support Grant CA16672, and an AstraZeneca Fellowship (X.X.). The M.D. Anderson Cancer Center has filed patent for the VISA-BikDD expression vector, which has been licensed to the ALchemgen Therapeutics Inc. (ATI). M.-C.H. also owns common stocks of ATI. This work was partially supported by ATI (to M.-C.H.). ",

year = "2007",

month = jul,

day = "10",

doi = "10.1016/j.ccr.2007.05.009",

language = "English (US)",

volume = "12",

pages = "52--65",

journal = "Cancer cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "1",

}

TY - JOUR

T1 - Targeted Expression of BikDD Eradicates Pancreatic Tumors in Noninvasive Imaging Models

AU - Xie, Xiaoming

AU - Xia, Weiya

AU - Li, Zhongkui

AU - Kuo, Hsu Ping

AU - Liu, Yuanfang

AU - Li, Zheng

AU - Ding, Qingqing

AU - Zhang, Su

AU - Spohn, Bill

AU - Yang, Yan

AU - Wei, Yongkun

AU - Lang, Jing Yu

AU - Evans, Douglas B.

AU - Chiao, Paul J.

AU - Abbruzzese, James L.

AU - Hung, Mien Chie

N1 - Funding Information: We thank Dr. Michael Carey (University of California Los Angeles School of Medicine, Los Angeles, CA) for providing the pGL3-TSTA-Luc vector; Dr. James B. Uney (University of Bristol, Bristol, United Kingdom) for providing the pGEM-3Z-WPRE vector; the biochemistry laboratory in the Department of Veterinary Medicine and Surgery for measuring serum AST, ALT, and BUN; and the Department of Scientific Publications at M.D. Anderson Cancer Center for editing this manuscript. This work was supported by an NIH SPORE grant in Pancreatic Cancer (P20 CA101936), a grant from Topfer Funds (M.-C.H. and J.L.A.), M.D. Anderson Cancer Center Support Grant CA16672, and an AstraZeneca Fellowship (X.X.). The M.D. Anderson Cancer Center has filed patent for the VISA-BikDD expression vector, which has been licensed to the ALchemgen Therapeutics Inc. (ATI). M.-C.H. also owns common stocks of ATI. This work was partially supported by ATI (to M.-C.H.).

PY - 2007/7/10

Y1 - 2007/7/10

N2 - 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.

AB - 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.

KW - CELLCYCLE

UR - https://www.scopus.com/pages/publications/34347263711

UR - https://www.scopus.com/pages/publications/34347263711#tab=citedBy

U2 - 10.1016/j.ccr.2007.05.009

DO - 10.1016/j.ccr.2007.05.009

M3 - Article

C2 - 17613436

AN - SCOPUS:34347263711

SN - 1535-6108

VL - 12

SP - 52

EP - 65

JO - Cancer cell

JF - Cancer cell

IS - 1

ER -

Targeted Expression of BikDD Eradicates Pancreatic Tumors in Noninvasive Imaging Models

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

Access to Document

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