title: Inhibition of spontaneous and experimental lung metastasis of soft-tissue sarcoma by tumor-targeting Salmonella typhimurium A1-R.
abstract: 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.
authors.affiliation: AntiCancer, Inc., San Diego, California, USA. Department of Surgery, University of California, San Diego, San Diego, California, USA. Department of Orthopedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Miwa
authors.affiliation: AntiCancer, Inc., San Diego, California, USA. Department of Surgery, University of California, San Diego, San Diego, California, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: AntiCancer, Inc., San Diego, California, USA.
authors.forename: Kyung-Eun
authors.initials: KE
authors.lastname: Baek
authors.affiliation: AntiCancer, Inc., San Diego, California, USA. Department of Surgery, University of California, San Diego, San Diego, California, USA.
authors.forename: Fuminari
authors.initials: F
authors.lastname: Uehara
authors.affiliation: AntiCancer, Inc., San Diego, California, USA. Department of Surgery, University of California, San Diego, San Diego, California, USA.
authors.forename: Shuya
authors.initials: S
authors.lastname: Yano
authors.affiliation: AntiCancer, Inc., San Diego, California, USA. Department of Surgery, University of California, San Diego, San Diego, California, USA.
authors.forename: Mako
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: AntiCancer, Inc., San Diego, California, USA. Department of Surgery, University of California, San Diego, San Diego, California, USA.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hiroshima
authors.affiliation: AntiCancer, Inc., San Diego, California, USA. Department of Surgery, University of California, San Diego, San Diego, California, USA.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Department of Orthopedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Department of Orthopedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Orthopedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Surgery, University of California, San Diego, San Diego, California, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
authors.affiliation: Department of Orthopedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuchiya
authors.affiliation: AntiCancer, Inc., San Diego, California, USA. Department of Surgery, University of California, San Diego, San Diego, California, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.affiliation: AntiCancer, Inc., San Diego, California, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005354:Fibrosarcoma / Q000382:microbiology / Q000473:pathology / Q000628:therapy; D006801:Humans; D008175:Lung Neoplasms / Q000382:microbiology / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D011379:Prognosis; D012486:Salmonella typhimurium / Q000502:physiology*; D012509:Sarcoma / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays