IR@PKUHSC  > 北京大学基础医学院  > 细胞生物学系
学科主题基础医学
Systemic NK4 gene therapy inhibits tumor growth and metastasis of melanoma and lung carcinoma in syngeneic mouse tumor models
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
2009-07-01
DOI10.1111/j.1349-7006.2009.01184.x
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
WOS记录号WOS:000266982000029
引用统计
被引频次:19[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63358
专题北京大学基础医学院_细胞生物学系
北京大学基础医学院
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
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GB/T 7714
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.
APA Kishi, Yuko.,Kuba, Keiji.,Nakamura, Takahiro.,Wen, Jinhua.,Suzuki, Yoshinori.,...&Nakamura, Toshikazu.(2009).Systemic NK4 gene therapy inhibits tumor growth and metastasis of melanoma and lung carcinoma in syngeneic mouse tumor models.CANCER SCIENCE,100(7),1351-1358.
MLA Kishi, Yuko,et al."Systemic NK4 gene therapy inhibits tumor growth and metastasis of melanoma and lung carcinoma in syngeneic mouse tumor models".CANCER SCIENCE 100.7(2009):1351-1358.
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