Inhibition of spontaneous and experimental lung metastasis of soft-tissue sarcoma by tumor-targeting Salmonella typhimurium A1-R
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Shinji Miwa1,2,3, Yong Zhang1,2, Kyung-Eun Baek1, Fuminari Uehara1,2, Shuya Yano1,2, Mako Yamamoto1,2, Yukihiko Hiroshima1,2, Yasunori Matsumoto1,2, Hiroaki Kimura3, Katsuhiro Hayashi3, Norio Yamamoto3, Michael Bouvet2, Hiroyuki Tsuchiya3, Robert M. Hoffman1,2, Ming Zhao1
1AntiCancer, Inc., San Diego, California, USA
2Department of Surgery, University of California, San Diego, San Diego, California, USA
3Department of Orthopedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan
Robert M. Hoffman or Ming Zhao, e-mail: firstname.lastname@example.org
Keywords: HT-1080; orthotopic model; nude mice; lung metastasis; bacterial therapy
Received: August 22, 2014 Accepted: October 01, 2014 Published: December 30, 2014
Prognosis of patients with lung metastases of soft-tissue sarcoma is still poor. Therefore, novel systemic therapy is needed to improve the survival of soft-tissue sarcoma. In the present study, tumor-targeting therapy with a genetically-modified auxotrophic strain of Salmonella typhimurium, termed A1-R, was evaluated. Mouse models of primary soft tissue sarcoma and spontaneous lung metastasis were obtained by orthotopic intra-muscular injection of HT1080-RFP human fibrosarcoma cells. S. typhimurium A1-R was administered from day 14, once a week for two weeks. On day 28, lung samples were excised and observed with a fluorescence imaging system. The number of lung metastasis was 8.8 ± 3.4 in the untreated group and 0.8 ± 0.8 in the treated group (P = 0.024). A mouse model of experimental lung metastasis was obtained by tail vein injection of HT1080-RFP cells. The mice were treated with S. typhimurium A1-R (i.v.) on day 7, once a week for three weeks. S. typhimurium A1-R significantly reduced lung metastases and improved overall survival (P = 0.004). S. typhimurium A1-R bacterial therapy has future potential for treating advanced soft tissue sarcoma and improving prognosis of patients with lung metastasis.
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