PLoS ONE (Jan 2015)

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

  • 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

DOI
https://doi.org/10.1371/journal.pone.0134324
Journal volume & issue
Vol. 10, no. 8
p. e0134324

Abstract

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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.