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Tumor-Targeting Salmonella typhimurium A1-R Arrests a Chemo-Resistant Patient Soft-Tissue Sarcoma in Nude Mice
- Hiroshima, Yukihiko;
- Zhao, Ming;
- Zhang, Yong;
- Zhang, Nan;
- Maawy, Ali;
- Murakami, Takashi;
- Mii, Sumiyuki;
- Uehara, Fuminari;
- Yamamoto, Mako;
- Miwa, Shinji;
- Yano, Shuya;
- Momiyama, Masashi;
- Mori, Ryutaro;
- Matsuyama, Ryusei;
- Chishima, Takashi;
- Tanaka, Kuniya;
- Ichikawa, Yasushi;
- Bouvet, Michael;
- Endo, Itaru;
- Hoffman, Robert M
- Editor(s): Singh, Pankaj K
Published Web Location
https://doi.org/10.1371/journal.pone.0134324Abstract
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.
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