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学科主题: 临床医学
题名:
A novel triple-regulated oncolytic adenovirus carrying PDCD5 gene exerts potent antitumor efficacy on common human leukemic cell lines
作者: Xie, Min1,3; Niu, Ji-Hong1,3; Chang, Yan1,3; Qian, Qi-Jun2; Wu, Hong-Ping2; Li, Lin-Fang2; Zhang, Yao1,3; Li, Jin-Lan1,3; Huang, Xiao-Jun1,3; Ruan, Guo-Rui1,3
关键词: PDCD5 ; Gene therapy ; Conditionally replicating adenoviruses ; Leukemia ; Nude mice
刊名: APOPTOSIS
发表日期: 2009-09-01
DOI: 10.1007/s10495-009-0373-3
卷: 14, 期:9, 页:1086-1094
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]: EXPRESSION PROFILES ; HEPATOCELLULAR-CARCINOMA ; MYELOGENOUS LEUKEMIA ; CANCER-TREATMENT ; VIRAL THERAPY ; TUMOR-CELLS ; IN-VIVO ; HTERT ; APOPTOSIS ; METASTASIS
英文摘要:

PDCD5 (programmed cell death 5) accelerates apoptosis of certain tumor cells and the replication-defective Ad-PDCD5 may be a promising agent for enhancing chemosensitivity. In this study, a triple-regulated conditionally replicating adenoviruses (CRAd) carrying PDCD5 gene expression cassette, SG611-PDCD5, was engineered. In SG611-PDCD5, the E1a gene with a deletion of 24 nucleotides within CR2 region is controlled under the human telomerase reverse transcriptase (hTERT) promoter, the E1b gene expression is directed by the hypoxia response element (HRE), whereas the PDCD5 gene is controlled by the cytomegalovirus promoter. The tumor-selective replication of this virus and its antitumor efficacy were characterized in several leukemic cell lines in vitro and in xenograft models of human leukemic cell line in nude mice. It was found by RQ-RT-PCR assay that SG611-PDCD5 expressed PDCD5 efficiently in leukemic cells. In K562 tumor xenograft models, SG611-PDCD5 displayed a tumor killing capacity. At a dose of 1 x 10(9) plaque-forming units, SG611-PDCD5 alone could completely inhibit the tumor growth and more effective than replication-defective Ad-PDCD5. Histopathologic examination revealed that SG611-PDCD5 administration resulted in leukemic cell apoptosis. We concluded that the triple-regulated SG611-PDCD5, as a more potent and safer antitumor therapeutic, could provide a new strategy for leukemia biotherapy.

语种: 英语
所属项目编号: 30670894 ; 2006AA02A405
项目资助者: National Natural Science Foundation of China ; National High Technology Research and Development Program of China (863 Program)
WOS记录号: WOS:000268743500006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60146
Appears in Collections:北京大学第二临床医学院_血液科_期刊论文

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作者单位: 1.Peking Univ, Inst Hematol, Beijing 100044, Peoples R China
2.Peking Univ, Peoples Hosp Hematol, Beijing 100044, Peoples R China
3.Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Lab Viral & Gene Therapy, Shanghai 200438, Peoples R China

Recommended Citation:
Xie, Min,Niu, Ji-Hong,Chang, Yan,et al. A novel triple-regulated oncolytic adenovirus carrying PDCD5 gene exerts potent antitumor efficacy on common human leukemic cell lines[J]. APOPTOSIS,2009,14(9):1086-1094.
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