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Reduced angiogenesis in peritoneal dissemination of gastric cancer through gelatinase inhibition

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Abstract

Marimastat is a broad-spectrum matrix metalloproteinase (MMP) inhibitor that inhibits almost all major MMPs, key enzymes in gastric cancer invasion and metastasis. We investigated the ability of marimastat to inhibit tumor angiogenesis in the severe combined immuno-deficient (SCID) mouse/human gastric cancer model of peritoneal dissemination. A human stomach adenocarcinoma cell line, TMK-1, was injected intraperitoneally into SCID mice. On the 7th day after tumor inoculation, the administration of marimastat (27 mg/kg/day) was initiated and the treatment was continued for 2 weeks using subcutaneously-inoculating mini-osmotic pumps. On the 21st day, the mice were killed and the disseminated nodules were evaluated. Total weights, numbers, and the microvascular density of the disseminating nodules were significantly lower in mice treated with marimastat compared to the control group. Film in situ zymography demonstrated that net gelatinolytic activity in the tissues was weaker in treated-group nodules than in control-group nodules. Thus, our results suggested that marimastat inhibited peritoneal dissemination of human gastric cancer cells through inhibition of tumor angiogenesis, possibly involving the down-regulation of gelatinases, in SCID mice injected with human gastric cancer cells.

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Authors and Affiliations

  1. Department of Surgery, School of Medicine, Keio University, Tokyo, Japan

    Norihito Wada, Yoshihide Otani, Tetsuro Kubota, Masaru Kimata, Akiko Minagawa, Nobunari Yoshimizu, Yoshiro Saikawa, Masashi Yoshida, Toshiharu Furukawa & Masaki Kitajima

  2. Department of Surgery, National Tokyo Medical Center, Tokyo, Japan

    Norihito Wada

  3. Department of Pathology, School of Medicine, Keio University, Tokyo, Japan

    Kaori Kameyama & Yasunori Okada

  4. Department of Otolaryngology, School of Medicine, Keio University, Tokyo, Japan

    Masato Fujii

  5. Center for Diagnostic and Therapeutic Endoscopy, Keio University Hospital, Tokyo, Japan

    Koichiro Kumai

Authors
  1. Norihito Wada
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  2. Yoshihide Otani
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  3. Tetsuro Kubota
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  4. Masaru Kimata
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  5. Akiko Minagawa
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  6. Nobunari Yoshimizu
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  7. Kaori Kameyama
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  8. Yoshiro Saikawa
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  9. Masashi Yoshida
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  10. Toshiharu Furukawa
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  11. Masato Fujii
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  12. Koichiro Kumai
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  13. Yasunori Okada
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  14. Masaki Kitajima
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Correspondence to Yoshihide Otani.

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Wada, N., Otani, Y., Kubota, T. et al. Reduced angiogenesis in peritoneal dissemination of gastric cancer through gelatinase inhibition. Clin Exp Metastasis 20, 431–435 (2003). https://doi.org/10.1023/A:1025453500148

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  • DOI: https://doi.org/10.1023/A:1025453500148

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