Combining Tumor-Selective Bacterial Therapy with Salmonella typhimurium A1-R and Cancer Metabolism Targeting with Oral Recombinant Methioninase Regressed an Ewing’s Sarcoma in a Patient-Derived Orthotopic Xenograft Model
| Autor: | Takashi Chishima, Yuying Tan, Ryusei Matsuyama, Kentaro Miyake, Kei Kawaguchi, Scott D. Nelson, Zhiying Zhang, Shree Ram Singh, Robert M. Hoffman, Tasuku Kiyuna, Yukihiko Hiroshima, Michael Bouvet, Sahar Razmjooei, Shukuan Li, Yunfeng Li, Maryam Barangi, Ming Zhao, Fritz C. Eilber, Takashi Murakami, Hiromichi Oshiro, Takashi Higuchi, Sintawat Wangsiricharoen, Arun S. Singh, Itaru Endo, Qinghong Han |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Salmonella medicine.disease_cause law.invention 03 medical and health sciences 0302 clinical medicine Oral administration law Drug Discovery Medicine Pharmacology (medical) Tumor growth Doxorubicin Pharmacology business.industry Ewing's sarcoma General Medicine medicine.disease 030104 developmental biology Infectious Diseases Oncology 030220 oncology & carcinogenesis Cancer metabolism Cancer research Recombinant DNA Sarcoma business medicine.drug |
| Zdroj: | Chemotherapy. 63:278-283 |
| ISSN: | 1421-9794 0009-3157 |
| DOI: | 10.1159/000495574 |
| Popis: | Background: Ewing’s sarcoma (ES) is a recalcitrant disease in need of transformative therapeutics. Objectives: The aim of this study was to investigate the efficacy of tumor-selective Salmonella typhimurium A1-R combined with tumor metabolism targeting with oral administration of recombinant methioninase (o-rMETase), on an ES patient-derived orthotopic xenograft (PDOX) model. Methods: The ES PDOX models were previously established in the right chest wall. The ES PDOX models were randomized into 5 groups when the tumor volume reached 80 mm3: G1: untreated control; G2: doxorubicin; G3: S. typhimurium A1-R; G4: o-rMETase; G5: S. typhimurium A1-R combined with o-rMETase. All mice were sacrificed on day 15. Body weight and tumor volume were assessed twice a week. Results: S. typhimurium A1-R and o-rMETase respectively suppressed tumor growth as monotherapies (p = 0.050 and p = 0.032). S. typhimurium A1-R combined with o-rMETase regressed tumor growth significantly compared to untreated group on day 15 (p < 0.032). S. typhimurium A1-R combined with o-rMETase group was significantly more effective than S. typhimurium A1-R or o-rMETase monotherapy (p = 0.032, p = 0.032). Conclusions: The present results suggest that the combination of S. typhimurium A1-R and o-rMETase has promise to be a transformative therapy for ES. |
| Databáze: | OpenAIRE |
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