Gene-viral cancer therapy using dual-regulated oncolytic adenovirus with antiangiogenesis gene for increased efficacy

	Gene-viral cancer therapy using dual-regulated oncolytic adenovirus with antiangiogenesis gene for increased efficacy
	Su, CQ; Na, ML; Chen, J; Wang, XH; Liu, YJ; Wang, WG; Zhang, Q; Li, LF; Long, J; Liu, XY
刊名	MOLECULAR CANCER RESEARCH
	2008
卷号	6 期号:4 页码:568-575
通讯作者	Qian, QJ (reprint author), Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Lab Viral & Gene Therapy, Shanghai 200438, Peoples R China.,qianqj@sino-gene.cn
英文摘要	Conditionally replicative adenovirus (CRAD) represents a promising approach for cancer therapy. Several CRADs controlled by the human telomerase reverse transcriptase promoter have been developed. However, because of their replicative capacity, the importance of cancer specificity for CRADs needs to be further emphasized. In this study, we have developed a novel dual-regulated CRAD, CNHK500-mE, which has its E1a and E1b gene controlled by the human telomerase reverse transcriptase promoter and the hypoxia response element, respectively. It also carries a mouse endostatin expression cassette controlled by the cytomegalovirus promoter. These properties allow for increased cancer cell targeting specificity and decreased adverse side effects. We showed that CNHK500-mE preferentially replicated in cancer cells. Compared with a replication-defective vector carrying the same endostatin expression cassette, CNHK500-mE-mediated transgene expression level was markedly increased via viral replication within cancer cells. In the nasopharyngeal tumor xenograft model, CNHK500-mE injection resulted in antitumor efficacy at day 7 after therapy. Three weeks later, it led to significant inhibition of xenograft tumor growth due to the combined effects of viral oncolytic therapy and antiangiogenesis gene therapy. Pathologic examination showed that most cancer cells were positive for adenoviral capsid protein and for apoptotic terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling in the CNHK500-mE-treated tumor tissues, and the microvessels in these tumor tissues were diminished in quantity and abnormal in morphology. These results suggest that, as a potential cancer therapeutic agent, the CNHK500-mE is endowed with higher specificity to cancer cells and low cytotoxicity to normal cells.
学科主题	Oncology; Cell Biology
类目[WOS]	Oncology ; Cell Biology
关键词[WOS]	MURINE MAMMARY CARCINOMAS ; HEPATOCELLULAR-CARCINOMA ; REPLICATIVE ADENOVIRUS ; ANTITUMORAL EFFICACY ; PROSTATE-CANCER ; ENDOSTATIN ; HYPOXIA ; CELLS ; VIRUS ; MECHANISMS
收录类别	SCI
语种	英语
WOS记录号	WOS:000254905600006
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1367]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Su, CQ,Na, ML,Chen, J,et al. Gene-viral cancer therapy using dual-regulated oncolytic adenovirus with antiangiogenesis gene for increased efficacy[J]. MOLECULAR CANCER RESEARCH,2008,6(4):568-575.
APA	Su, CQ.,Na, ML.,Chen, J.,Wang, XH.,Liu, YJ.,...&Qian, QJ.(2008).Gene-viral cancer therapy using dual-regulated oncolytic adenovirus with antiangiogenesis gene for increased efficacy.MOLECULAR CANCER RESEARCH,6(4),568-575.
MLA	Su, CQ,et al."Gene-viral cancer therapy using dual-regulated oncolytic adenovirus with antiangiogenesis gene for increased efficacy".MOLECULAR CANCER RESEARCH 6.4(2008):568-575.