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Articles by S Suzuki
Total Records ( 3 ) for S Suzuki
  L. M Knowles , L. P Stabile , A. M Egloff , M. E Rothstein , S. M Thomas , C. T Gubish , E. C Lerner , R. R Seethala , S Suzuki , K. M Quesnelle , S Morgan , R. L Ferris , J. R Grandis and J. M. Siegfried

Purpose: We determined hepatocyte growth factor (HGF) and c-Met expression and signaling in human head and neck squamous cell carcinoma (HNSCC) cells and primary tissues and tested the ability of c-Met tyrosine kinase inhibitors (TKI) to block HGF-induced biological signaling.

Experimental Design: Expression and signaling were determined using immunoblotting, ELISA, and immunohistochemistry. Biological end points included wound healing, cell proliferation, and invasion. c-Met TKIs were tested for their ability to block HGF-induced signaling and biological effects in vitro and in xenografts established in nude mice.

Results: c-Met was expressed and functional in HNSCC cells. HGF was secreted by HNSCC tumor-derived fibroblasts, but not by HNSCC cells. Activation of c-Met promoted phosphorylation of AKT and mitogen-activated protein kinase as well as release of the inflammatory cytokine interleukin-8. Cell growth and wound healing were also stimulated by HGF. c-Met TKIs blocked HGF-induced signaling, interleukin-8 release, and wound healing. Enhanced invasion of HNSCC cells induced by the presence of tumor-derived fibroblasts was completely blocked with a HGF-neutralizing antibody. PF-2341066, a c-Met TKI, caused a 50% inhibition of HNSCC tumor growth in vivo with decreased proliferation and increased apoptosis within the tumors. In HNSCC tumor tissues, both HGF and c-Met protein were increased compared with expression in normal mucosa.

Conclusions: These results show that HGF acts mainly as a paracrine factor in HNSCC cells, the HGF/c-Met pathway is frequently up-regulated and functional in HNSCC, and a clinically relevant c-Met TKI shows antitumor activity in vivo. Blocking the HGF/c-Met pathway may be clinically useful for the treatment of HNSCC.

  K Ishiyama , A Takami , S Suzuki , H Konaka , M Namiki , A Ooi and S. Nakao

Renal cell carcinoma (RCC) is refractory to conventional therapy, including chemotherapy and radiation. However, because RCC is sensitive to cytokine therapy, an immunotherapeutic approach such as hematopoietic stem cell transplantation (HSCT) might lead to a cure. We performed an institutional clinical study of HSCT for refractory RCC patients.


RCC patients aged 50 years or over, refractory to therapy, were eligible for the study. HSCT was performed after reduced-intensity conditioning. Primary endpoint was defined as the survival at day 100 after HSCT with complete donor chimerism, and secondary endpoint was the effectiveness of HSCT.


Seven patients, provided with written informed consent, were enrolled in the study. Six of the seven patients achieved complete donor chimera at day 30 after HSCT, but one patient received second HSCT because of graft rejection. Four patients achieved a partial response (PR) and stable disease was observed in another patient, but these responses were temporary. The disease of the other two patients became progressive. Autopsy findings revealed an accumulation of CD8+ lymphocytes and degenerative changes in the local RCC lesion in three of six patients who responded clinically. An autopsy of a patient who had obtained a PR revealed lymphocyte involvement with a cytotoxic T cell (CTL) phenotype in the metastasis of RCC.


Our results demonstrate the efficacy of HSCT for RCC and suggest that the graft-versus-tumor effect elicited by CTLs is induced in vivo. HSCT should be further explored as a potential curative treatment for RCC.

  S Morikawa , Y Mabuchi , Y Kubota , Y Nagai , K Niibe , E Hiratsu , S Suzuki , C Miyauchi Hara , N Nagoshi , T Sunabori , S Shimmura , A Miyawaki , T Nakagawa , T Suda , H Okano and Y. Matsuzaki

Mesenchymal stem cells (MSCs) are defined as cells that undergo sustained in vitro growth and can give rise to multiple mesenchymal lineages. Because MSCs have only been isolated from tissue in culture, the equivalent cells have not been identified in vivo and little is known about their physiological roles or even their exact tissue location. In this study, we used phenotypic, morphological, and functional criteria to identify and prospectively isolate a subset of MSCs (PDGFR+Sca-1+CD45TER119) from adult mouse bone marrow. Individual MSCs generated colonies at a high frequency and could differentiate into hematopoietic niche cells, osteoblasts, and adipocytes after in vivo transplantation. Naive MSCs resided in the perivascular region in a quiescent state. This study provides the useful method needed to identify MSCs as defined in vivo entities.

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