Exquisite Tumor Targeting by Salmonella A1-R in Combination with Caffeine and Valproic Acid Regresses an Adult Pleomorphic Rhabdomyosarcoma Patient-Derived Orthotopic Xenograft Mouse Model
Adult pleomorphic rhabdomyosarcoma (RMS) is a rare and malignant mesenchymal tumor. Recently, we developed a patient-derived orthotopic xenograft (PDOX) model of adult pleomorphic RMS. In the present study, we evaluated the efficacy of tumor-targeting Salmonella typhimurium (S. typhimurium) A1-R com...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-02-01
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| Series: | Translational Oncology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523319305030 |
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doaj-cddf69c1a2c246edb97111bbb042292c |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Kentaro Igarashi Kei Kawaguchi Ming Zhao Tasuku Kiyuna Kentaro Miyake Masuyo Miyake Scott D. Nelson Sarah M. Dry Yunfeng Li Norio Yamamoto Katsuhiro Hayashi Hiroaki Kimura Shinji Miwa Takashi Higuchi Shree Ram Singh Hiroyuki Tsuchiya Robert M. Hoffman |
| spellingShingle |
Kentaro Igarashi Kei Kawaguchi Ming Zhao Tasuku Kiyuna Kentaro Miyake Masuyo Miyake Scott D. Nelson Sarah M. Dry Yunfeng Li Norio Yamamoto Katsuhiro Hayashi Hiroaki Kimura Shinji Miwa Takashi Higuchi Shree Ram Singh Hiroyuki Tsuchiya Robert M. Hoffman Exquisite Tumor Targeting by Salmonella A1-R in Combination with Caffeine and Valproic Acid Regresses an Adult Pleomorphic Rhabdomyosarcoma Patient-Derived Orthotopic Xenograft Mouse Model Translational Oncology |
| author_facet |
Kentaro Igarashi Kei Kawaguchi Ming Zhao Tasuku Kiyuna Kentaro Miyake Masuyo Miyake Scott D. Nelson Sarah M. Dry Yunfeng Li Norio Yamamoto Katsuhiro Hayashi Hiroaki Kimura Shinji Miwa Takashi Higuchi Shree Ram Singh Hiroyuki Tsuchiya Robert M. Hoffman |
| author_sort |
Kentaro Igarashi |
| title |
Exquisite Tumor Targeting by Salmonella A1-R in Combination with Caffeine and Valproic Acid Regresses an Adult Pleomorphic Rhabdomyosarcoma Patient-Derived Orthotopic Xenograft Mouse Model |
| title_short |
Exquisite Tumor Targeting by Salmonella A1-R in Combination with Caffeine and Valproic Acid Regresses an Adult Pleomorphic Rhabdomyosarcoma Patient-Derived Orthotopic Xenograft Mouse Model |
| title_full |
Exquisite Tumor Targeting by Salmonella A1-R in Combination with Caffeine and Valproic Acid Regresses an Adult Pleomorphic Rhabdomyosarcoma Patient-Derived Orthotopic Xenograft Mouse Model |
| title_fullStr |
Exquisite Tumor Targeting by Salmonella A1-R in Combination with Caffeine and Valproic Acid Regresses an Adult Pleomorphic Rhabdomyosarcoma Patient-Derived Orthotopic Xenograft Mouse Model |
| title_full_unstemmed |
Exquisite Tumor Targeting by Salmonella A1-R in Combination with Caffeine and Valproic Acid Regresses an Adult Pleomorphic Rhabdomyosarcoma Patient-Derived Orthotopic Xenograft Mouse Model |
| title_sort |
exquisite tumor targeting by salmonella a1-r in combination with caffeine and valproic acid regresses an adult pleomorphic rhabdomyosarcoma patient-derived orthotopic xenograft mouse model |
| publisher |
Elsevier |
| series |
Translational Oncology |
| issn |
1936-5233 |
| publishDate |
2020-02-01 |
| description |
Adult pleomorphic rhabdomyosarcoma (RMS) is a rare and malignant mesenchymal tumor. Recently, we developed a patient-derived orthotopic xenograft (PDOX) model of adult pleomorphic RMS. In the present study, we evaluated the efficacy of tumor-targeting Salmonella typhimurium (S. typhimurium) A1-R combined with caffeine (CAF) and valproic acid (VPA) on the adult RMS PDOX. An adult pleomorphic RMS cell line was established from the PDOX model. Cell survival after exposure to CAF and VPA was assessed, and the IC50 value was calculated for each drug. The RMS PDOX models were randomized into five groups: untreated control; tumor treated with cyclophosphamide (CPA); tumor treated with CAF + VPA; tumor treated with S. typhimurium A1-R; and tumor treated with S. typhimurium A1-R + CAF + VPA. Tumor size and body weight was measured twice a week. VPA caused a concentration-dependent cytocidal effect. A synergistic effect of combination treatment with CAF was observed against the RMS cell line. For the in vivo study, all treatments significantly inhibited tumor growth compared with the untreated control. S. typhimurium A1-R combined with VPA and CAF was significantly more effective than CPA, VPA combined with CAF, or S. typhimurium A1-R alone and significantly regressed the tumor volume compared with day 0. These results suggest that S. typhimurium A1-R together with VPA and CAF could regresses an adult pleomorphic RMS in a PDOX model and therefore has important future clinical potential. |
| url |
http://www.sciencedirect.com/science/article/pii/S1936523319305030 |
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doaj-cddf69c1a2c246edb97111bbb042292c2020-11-25T02:06:20ZengElsevierTranslational Oncology1936-52332020-02-01132393400Exquisite Tumor Targeting by Salmonella A1-R in Combination with Caffeine and Valproic Acid Regresses an Adult Pleomorphic Rhabdomyosarcoma Patient-Derived Orthotopic Xenograft Mouse ModelKentaro Igarashi0Kei Kawaguchi1Ming Zhao2Tasuku Kiyuna3Kentaro Miyake4Masuyo Miyake5Scott D. Nelson6Sarah M. Dry7Yunfeng Li8Norio Yamamoto9Katsuhiro Hayashi10Hiroaki Kimura11Shinji Miwa12Takashi Higuchi13Shree Ram Singh14Hiroyuki Tsuchiya15Robert M. Hoffman16AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, JapanAntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USAAntiCancer, Inc., San Diego, CA, USAAntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USAAntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USAAntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USADepartment of Pathology, University of California, Los Angeles, CA, USADepartment of Pathology, University of California, Los Angeles, CA, USADepartment of Pathology, University of California, Los Angeles, CA, USADepartment of Orthopaedic Surgery, Kanazawa University, Kanazawa, JapanDepartment of Orthopaedic Surgery, Kanazawa University, Kanazawa, JapanDepartment of Orthopaedic Surgery, Kanazawa University, Kanazawa, JapanDepartment of Orthopaedic Surgery, Kanazawa University, Kanazawa, JapanAntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, JapanBasic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA; Address all correspondence to: Shree Ram Singh, PhD, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan; Hiroyuki Tsuchiya, MD, PhD, Department of Orthopaedic Surgery, Graduate School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Robert M. Hoffman, PhD, AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA 92111, USA.Adult pleomorphic rhabdomyosarcoma (RMS) is a rare and malignant mesenchymal tumor. Recently, we developed a patient-derived orthotopic xenograft (PDOX) model of adult pleomorphic RMS. In the present study, we evaluated the efficacy of tumor-targeting Salmonella typhimurium (S. typhimurium) A1-R combined with caffeine (CAF) and valproic acid (VPA) on the adult RMS PDOX. An adult pleomorphic RMS cell line was established from the PDOX model. Cell survival after exposure to CAF and VPA was assessed, and the IC50 value was calculated for each drug. The RMS PDOX models were randomized into five groups: untreated control; tumor treated with cyclophosphamide (CPA); tumor treated with CAF + VPA; tumor treated with S. typhimurium A1-R; and tumor treated with S. typhimurium A1-R + CAF + VPA. Tumor size and body weight was measured twice a week. VPA caused a concentration-dependent cytocidal effect. A synergistic effect of combination treatment with CAF was observed against the RMS cell line. For the in vivo study, all treatments significantly inhibited tumor growth compared with the untreated control. S. typhimurium A1-R combined with VPA and CAF was significantly more effective than CPA, VPA combined with CAF, or S. typhimurium A1-R alone and significantly regressed the tumor volume compared with day 0. These results suggest that S. typhimurium A1-R together with VPA and CAF could regresses an adult pleomorphic RMS in a PDOX model and therefore has important future clinical potential.http://www.sciencedirect.com/science/article/pii/S1936523319305030 |