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Suppression of peritoneal implantation of gastric cancer cells by adenovirus vector-mediated NK4 expression

Cancer Gene Therapy volume 12, pages 206–216 (2005)Cite this article

Abstract

Peritoneal dissemination is the most common mode of metastasis in gastric cancer. We previously reported the importance of milky spots (MS), peritoneal lymphoid tissues, as selective sites of cancer implantation in peritoneal dissemination. In the present study, we first demonstrated that intraperitoneal injection of adenovirus vector encoding the GFP gene into tumor-free nude mice resulted in GFP expression at omental and mesenteric MS; MS macrophages were target cells for adenovirus infection. We confirmed that intraperitoneal injection of adenovirus vector encoding the NK4 gene (AdNK4) resulted in NK4 production localized to the peritoneal cavity, especially the omentum. Adenovirus vector-mediated MS-selective transgene expression was markedly impaired in tumor-bearing mice whose MS had already been replaced by infiltrating cancer cells. However, prior injection of AdNK4 successfully inhibited MS-selective cancer cell implantation, resulting in suppression of peritoneal dissemination and prolongation of survival. Adenovirus vector-mediated MS-selective delivery of a therapeutic gene may prevent peritoneal dissemination of gastric cancer.

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Acknowledgements

This study was supported by a Grant-in-Aid for Young Scientists and a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Author notes

  1. Hitoshi Fujiwara and Takeshi Kubota: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Hitoshi Fujiwara, Takeshi Kubota, Hisashi Amaike, Satoshi Inada, Kazuhiro Takashima, Kiyoto Atsuji, Mamoru Yoshimura, Akeo Hagiwara & Hisakazu Yamagishi

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

    Makoto Maemondo, Ko Narumi & 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. Hitoshi Fujiwara
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Correspondence to Hitoshi Fujiwara.

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Fujiwara, H., Kubota, T., Amaike, H. et al. Suppression of peritoneal implantation of gastric cancer cells by adenovirus vector-mediated NK4 expression. Cancer Gene Ther 12, 206–216 (2005). https://doi.org/10.1038/sj.cgt.7700782

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