Tumor-Targeting Salmonella typhimurium A1-R Arrests a Chemo-Resistant Patient Soft-Tissue Sarcoma in Nude Mice

• DOI: 10.1371/journal.pone.0134324
• Publication Date: 2015-08-03T17:40:02Z
• Authors: Yukihiko Hiroshima; Ming Zhao; Yong Zhang; Nan Zhang; Ali Maawy; Takashi Murakami; Sumiyuki Mii; Fuminari Uehara; Mako Yamamoto; Shinji Miwa; Shuya Yano; Masashi Momiyama; Ryutaro Mori; Ryusei Matsuyama; Takashi Chishima; Kuniya Tanaka; Yasushi Ichikawa; Michael Bouvet; Itaru Endo; Robert M. Hoffman
• Keywords: Salmonella typhimurium; 0301 basic medicine; Indazoles; General Science & Technology; Science; Nude; 610; Mice, Nude; Antineoplastic Agents; Soft Tissue Neoplasms; Deoxycytidine; Mice; 03 medical and health sciences; Rare Diseases; Animals; Cancer; Sulfonamides; Animal; Q; R; Sarcoma; Xenograft Model Antitumor Assays; Gemcitabine; 3. Good health; Disease Models, Animal; Emerging Infectious Diseases; Orphan Drug; Pyrimidines; Disease Models; Salmonella Infections; Medicine; Digestive Diseases; Research Article

A patient-derived nude-mouse model of soft-tissue sarcoma has been established and treated in the following groups: (1) untreated controls; (2) gemcitabine (GEM) (80 mg/kg, ip, weekly, 3 weeks); (3) Pazopanib (100 mg/kg, orally, daily, 3 weeks) and (4) Salmonella typhimurium A1-R (5 × 10(7) CFU/body, ip, weekly, 3 weeks). The sarcoma was resistant to GEM (p = 0.879). Pazopanib tended to reduce the tumor volume compared to the untreated mice, but there was no significant difference (p = 0.115). S. typhimurium A1-R significantly inhibited tumor growth compared to the untreated mice (p = 0.001). S. typhimurium A1-R was the only effective treatment for the soft-tissue sarcoma nude mouse model among all treatments including a newly approved multiple tyrosine kinase inhibitor; Pazopanib. These results suggest tumor-targeting S. typhimurium A1-R is a promising treatment for chemo-resistant soft-tissue sarcoma.