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:10.1371/journal.pone.0134324

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

Research output: Contribution to journal › Article › peer-review

67 Citations (Scopus)

Abstract

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 × 10⁷ 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 chemoresistant soft-tissue sarcoma.

Original language	English
Article number	e0134324
Journal	PloS one
Volume	10
Issue number	8
DOIs	https://doi.org/10.1371/journal.pone.0134324
Publication status	Published - Aug 3 2015
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
General

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Hiroshima, Y., Zhao, M., Zhang, Y., Zhang, N., Maawy, A., Murakami, T., Mii, S., Uehara, F., Yamamoto, M., Miwa, S., Yano, S., Momiyama, M., Mori, R., Matsuyama, R., Chishima, T., Tanaka, K., Ichikawa, Y., Bouvet, M., Endo, I., & Hoffman, R. M. (2015). Tumor-targeting salmonella typhimurium A1-R arrests a chemo-resistant patient soft-tissue sarcoma in nude mice. PloS one, 10(8), [e0134324]. https://doi.org/10.1371/journal.pone.0134324

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.

In: PloS one, Vol. 10, No. 8, e0134324, 03.08.2015.

Research output: Contribution to journal › Article › peer-review

Hiroshima, Y, Zhao, M, Zhang, Y, Zhang, N, Maawy, A, Murakami, T, Mii, S, Uehara, F, Yamamoto, M, Miwa, S, Yano, S, Momiyama, M, Mori, R, Matsuyama, R, Chishima, T, Tanaka, K, Ichikawa, Y, Bouvet, M, Endo, I & Hoffman, RM 2015, 'Tumor-targeting salmonella typhimurium A1-R arrests a chemo-resistant patient soft-tissue sarcoma in nude mice', PloS one, vol. 10, no. 8, e0134324. https://doi.org/10.1371/journal.pone.0134324

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. / Tumor-targeting salmonella typhimurium A1-R arrests a chemo-resistant patient soft-tissue sarcoma in nude mice. In: PloS one. 2015 ; Vol. 10, No. 8.

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abstract = "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 × 107 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 chemoresistant soft-tissue sarcoma.",

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Tumor-targeting salmonella typhimurium A1-R arrests a chemo-resistant patient soft-tissue sarcoma in nude mice

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