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VEGF receptor antisense therapy inhibits angiogenesis and peritoneal dissemination of human gastric cancer in nude mice

Cancer Gene Therapy volume 9, pages 197–201 (2002)Cite this article

Abstract

The efficacy of a phosphorothioate antisense oligonucleotide (ASO) for KDR/Flk-1 (KDR/Flk-1-ASO), an endothelial cell–specific vascular endothelial growth factor (VEGF) receptor, was investigated on the peritoneal dissemination and angiogenesis of a human gastric cancer cell line in nude mice. Green fluorescent protein (GFP)–transduced NUGC-4 (NUGC-4-GFP) human gastric cancer cells were implanted into the peritoneal cavity of nude mice. KDR/Flk-1-ASO, -SO, or phosphate-buffered saline was administrated from days 7 to 14, 200 μg/mouse, once a day. The mice were sacrificed on day 28. Disseminated peritoneal tumor nodules expressing GFP were visualized by fluorescence microscopy. KDR/Flk-1-ASO significantly decreased the extent of peritoneal dissemination of the tumors. The number of cells undergoing apoptosis was significantly increased in the KDR/Flk-1-ASO–treated tumors. Microvessel density was significantly reduced in the KDR/Flk-1-ASO–treated tumor nodules. The KDR/Flk-1 antisense strategy, therefore, decreases tumor dissemination apparently by inhibiting angiogenesis.

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Acknowledgements

This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan (11671260).

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Authors and Affiliations

  1. Department of Surgery II, Yokohama City University, School of Medicine, Yokohama, Japan

    Masako Kamiyama, Yasushi Ichikawa, Takashi Ishikawa, Takashi Chishima, Satoshi Hasegawa, Yohei Hamaguchi, Shigeo Ohki & Hiroshi Shimada

  2. Department of Pathology II, Yokohama City University, School of Medicine, Yokohama, Japan

    Yoji Nagashima & Yohei Miyagi

  3. HYBsimulator software, RNAture, Irvine, California, USA

    Masato Mitsuhashi

  4. Hitachi Chemical Research Center, Irvine, California, USA

    David Hyndman

  5. AntiCancer Inc., San Diego, California, USA

    Robert M Hoffman

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  1. Masako Kamiyama
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  2. Yasushi Ichikawa
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  3. Takashi Ishikawa
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  4. Takashi Chishima
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  11. Robert M Hoffman
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  12. Shigeo Ohki
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  13. Hiroshi Shimada
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Correspondence to Robert M Hoffman.

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Kamiyama, M., Ichikawa, Y., Ishikawa, T. et al. VEGF receptor antisense therapy inhibits angiogenesis and peritoneal dissemination of human gastric cancer in nude mice. Cancer Gene Ther 9, 197–201 (2002). https://doi.org/10.1038/sj.cgt.7700428

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