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学科主题: 基础医学
题名:
Systemic NK4 gene therapy inhibits tumor growth and metastasis of melanoma and lung carcinoma in syngeneic mouse tumor models
作者: Kishi, Yuko1; Kuba, Keiji1,2; Nakamura, Takahiro3; Wen, Jinhua4,5; Suzuki, Yoshinori3; Mizuno, Shinya1; Nukiwa, Toshihiro6; Matsumoto, Kunio3; Nakamura, Toshikazu1,7
刊名: CANCER SCIENCE
发表日期: 2009-07-01
DOI: 10.1111/j.1349-7006.2009.01184.x
卷: 100, 期:7, 页:1351-1358
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: HUMAN PANCREATIC-CANCER ; ANTITUMOR-ACTIVITY ; COLON-CANCER ; NUDE-MICE ; 4-KRINGLE ANTAGONIST ; MET KINASE ; HEPATOCYTE ; CELLS ; ANGIOGENESIS ; INJECTION
英文摘要:

Hepatocyte growth factor (HGF) promotes malignant development of cancer cells by enhancing invasion and metastasis. NK4, a competitive antagonist for HGF, is a bifunctional molecule that acts as a HGF antagonist and angiogenesis inhibitor. Although successful tumor inhibition by NK4 gene expression in tumor models has been demonstrated, the effects of systemic NK4 gene introduction are yet to be addressed. Here we show that systemic administration of a replication-defective adenovirus expressing NK4 (Ad.NK4) inhibits tumor growth and lung metastasis of B16F10 melanoma and Lewis lung carcinoma in syngeneic mice. Single tail-vein injection of Ad.NK4 achieved therapeutic levels of NK4 in the circulation and in multiple organs. Despite NK4 expression that was highest in the liver, toxicity in the liver was minimal. Ad.NK4-mediated growth inhibition was associated with decreased blood vessel density and increased apoptosis in tumor tissues, which suggests that NK4 suppressed tumor growth as an angiogenesis inhibitor. Metastasis of B16F10 melanoma and Lewis lung carcinoma cells to the lung was potently inhibited by systemic Ad.NK4-administration. Our results demonstrated that the adenovirus-mediated induction of high levels of circulating NK4 significantly inhibited in vivo tumor growth and distant metastasis without obvious side effects. NK4 gene therapy is thus a safe and promising strategy for the treatment of cancer patients, and further validation in clinical trials is needed. (Cancer Sci 2009; 100: 1351-1358)

语种: 英语
所属项目编号: 18013031 ; 18015031 ; 19890062
项目资助者: Ministry of Education, Culture, Science, Sports, and Technology of Japan ; 21st Century global COE program ; National Institute of Biomedical Innovation ; Takeda Science Foundation
WOS记录号: WOS:000266982000029
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63358
Appears in Collections:基础医学院_细胞生物学系_期刊论文

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作者单位: 1.Osaka Univ, Sch Med, Div Mol Regenerat Med, Osaka, Japan
2.Akita Univ, Grad Sch Med, Div Mol Pharmacol & Expt Therapeut, Dept Physiol & Pharmacol, Akita 010, Japan
3.Kanazawa Univ, Canc Res Inst, Div Tumor Dynam & Regulat, Kanazawa, Ishikawa 920, Japan
4.Peking Univ, Hlth Sci Ctr, Peking Univ Stem Cell Res Ctr, Beijing 100871, Peoples R China
5.Peking Univ, Hlth Sci Ctr, Dept Cell Biol, Beijing 100871, Peoples R China
6.Tohoku Univ, Inst Dev Aging & Canc, Dept Resp Oncol & Mol Med, Sendai, Miyagi 980, Japan
7.Osaka Univ, Ctr Adv Sci & Innovat, Kringle Pharma Joint Res Div Regenerat Drug Disco, Osaka, Japan

Recommended Citation:
Kishi, Yuko,Kuba, Keiji,Nakamura, Takahiro,et al. Systemic NK4 gene therapy inhibits tumor growth and metastasis of melanoma and lung carcinoma in syngeneic mouse tumor models[J]. CANCER SCIENCE,2009,100(7):1351-1358.
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