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Gallbladder cancer treatment using adenovirus expressing the HGF/NK4 gene in a peritoneal implantation model

Cancer Gene Therapy volume 11, pages 431–440 (2004)Cite this article

Abstract

Gallbladder cancer cells are stimulated by hepatocyte growth factor (HGF) in vitro and in vivo. We constructed an adenovirus vector, AdCMV.NK4, carrying the HGF antagonist HGF/NK4 (NK4) and evaluated whether or not this vector can suppress the peritoneal implantation of gallbladder cancer in a novel peritoneal injury mouse model. A human gallbladder cancer cell line (GB-d1) and human peritoneal mesothelial cells infected with the adenovirus vector produced a substantial level of NK4 protein. An invasion of GB-d1 cells was determined by a coculture with AdCMV.NK4-infected human mesothelial cells in vitro. Both the invasion and migration of GB-d1 cells were dramatically inhibited by this vector in a multiplicity of infection (MOI)-dependent manner. GB-d1 cells were intraperitoneally injected into the nude mice with peritoneal injury, followed by either AdCMV.NK4 or a control vector (AdCMV.LacZ). The incidence and the size of the metastatic tumor drastically decreased by AdCMV.NK4 (MOI 100: n=4, P<.0001). Real-time PCR analysis revealed a transient elevation of mouse HGF mRNA expression at the peritoneal injury sites. AdCMV.NK4 has been suggested to induce the inhibition of the implantation and growth of gallbladder cancer cells in vivo through its anti-HGF activity, and the use of NK4 gene transfer could be an effective modality for preventing peritoneal metastasis of gallbladder cancer.

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Acknowledgements

This work was supported, in part, by a Grant- in- Aid from the Ministry of Education, Science, Sports and Culture of Japan.

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Authors and Affiliations

  1. First Department of Surgery, Fukuoka University School of Medicine, Fukuoka, 814-0180, Japan

    Toshihiro Tanaka, Hideo Shimura, Takamitsu Sasaki & Seiyo Ikeda

  2. Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, Miyagi, Japan

    Kou Narumi, Makoto Maemondo & Toshihiro Nukiwa

  3. Division of Molecular Regenerative Medicine, Course of Advanced Medicine Osaka University Graduate School of Medicine, Osaka, Japan

    Kunio Matsumoto & Toshikazu Nakamura

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  1. Toshihiro Tanaka
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  2. Hideo Shimura
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  3. Takamitsu Sasaki
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Correspondence to Hideo Shimura.

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Tanaka, T., Shimura, H., Sasaki, T. et al. Gallbladder cancer treatment using adenovirus expressing the HGF/NK4 gene in a peritoneal implantation model. Cancer Gene Ther 11, 431–440 (2004). https://doi.org/10.1038/sj.cgt.7700714

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