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Tumor-targeting Salmonella typhimurium A1-R regresses an osteosarcoma in a patient-derived xenograft model resistant to a molecular-targeting drug.
- Murakami, Takashi;
- Igarashi, Kentaro;
- Kawaguchi, Kei;
- Kiyuna, Tasuku;
- Zhang, Yong;
- Zhao, Ming;
- Hiroshima, Yukihiko;
- Nelson, Scott D;
- Dry, Sarah M;
- Li, Yunfeng;
- Yanagawa, Jane;
- Russell, Tara;
- Federman, Noah;
- Singh, Arun;
- Elliott, Irmina;
- Matsuyama, Ryusei;
- Chishima, Takashi;
- Tanaka, Kuniya;
- Endo, Itaru;
- Eilber, Fritz C;
- Hoffman, Robert M
- et al.
Published Web Location
https://doi.org/10.18632/oncotarget.14040Abstract
Osteosarcoma occurs mostly in children and young adults, who are treated with multiple agents in combination with limb-salvage surgery. However, the overall 5-year survival rate for patients with recurrent or metastatic osteosarcoma is 20-30% which has not improved significantly over 30 years. Refractory patients would benefit from precise individualized therapy. We report here that a patient-derived osteosarcoma growing in a subcutaneous nude-mouse model was regressed by tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R, p<0.001 compared to untreated control). The osteosarcoma was only partially sensitive to the molecular-targeting drug sorafenib, which did not arrest its growth. S. typhimurium A1-R was significantly more effective than sorafenib (P <0.001). S. typhimurium grew in the treated tumors and caused extensive necrosis of the tumor tissue. These data show that S. typhimurium A1-R is powerful therapy for an osteosarcoma patient-derived xenograft model.
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