Therapeutic efficacy of tumor-targeting Salmonella typhimurium A1-R on human colorectal cancer liver metastasis in orthotopic nude-mouse models
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Takashi Murakami1,2,3, Yukihiko Hiroshima1,2,3, Ming Zhao1, Yong Zhang1, Takashi Chishima3, Kuniya Tanaka3, Michael Bouvet2, Itaru Endo3, Robert M. Hoffman1,2
1AntiCancer, Inc., San Diego, California, USA
2Department of Surgery, University of California San Diego, California, USA
3Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan
Robert M. Hoffman, e-mail: email@example.com
Keywords: nude mice, orthotopic, liver metastasis, red fluorescent protein, Salmonella typhimurium A1-R
Received: June 30, 2015 Accepted: August 25, 2015 Published: September 07, 2015
Liver metastasis is the most frequent cause of death from colon and other cancers. Generally, liver metastasis is recalcitrant to treatment. The aim of this study is to determine the efficacy of tumor-targeting Salmonella typhimurium A1-R on liver metastasis in orthotopic mouse models. HT-29 human colon cancer cells expressing red fluorescent protein (RFP) were used in the present study. S. typhimurium A1-R infected HT-29 cells in a time-dependent manner, inhibiting cancer-cell proliferation in vitro. S. typhimurium A1-R promoted tumor necrosis and inhibited tumor growth in a subcutaneous tumor mouse model of HT-29-RFP. In orthotopic mouse models, S. typhimurium A1-R targeted liver metastases and significantly reduced their growth. The results of this study demonstrate the future clinical potential of S. typhimurium A1-R targeting of liver metastasis.
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