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Adenoviral-mediated Gene transduction of the hepatocyte growth factor (HGF) antagonist, NK4, suppresses peritoneal metastases of gastric cancer in nude mice

The competitive inhibitory effects of NK4 (a specific hepatocyte growth factor (HGF)-antagonist) on the interaction between HGF and the c-Met/HGF receptor has been shown in HGF-mediated invasion of some distinct types of human cancer cells. Furthermore, NK4 has inhibitory effects on the angiogenic p...

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Published in:European journal of cancer (1990) 2004-09, Vol.40 (14), p.2135-2142
Main Authors: Ueda, Kentaro, Iwahashi, Makoto, Matsuura, Ichiro, Nakamori, Mikihito, Nakamura, Masaki, Ojima, Toshiyasu, Naka, Teiji, Ishida, Koichiro, Matsumoto, Kunio, Nakamura, Toshikazu, Yamaue, Hiroki
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Language:English
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Summary:The competitive inhibitory effects of NK4 (a specific hepatocyte growth factor (HGF)-antagonist) on the interaction between HGF and the c-Met/HGF receptor has been shown in HGF-mediated invasion of some distinct types of human cancer cells. Furthermore, NK4 has inhibitory effects on the angiogenic pathways driven by basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), as well as by HGF. In this study, to evaluate the therapeutic efficacy of adenoviral-mediated NK4 gene treatment, we employed animal models of peritoneal metastasis using two gastric cancer cell lines, the strongly c-Met expressing MKN45 cell line and the weakly c-Met-expressing cell line, TMK1. In both models, the total number and weight of peritoneal tumours per mouse and ascites treated early with AxCANK4 (administered 3 times 2, 7 and 12 days after the tumour inoculation) were significantly reduced compared with those treated with phosphate-buffered solution (PBS) and AxCALacZ ( P
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2004.05.006