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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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Autores principales: Igarashi, Kentaro, Kawaguchi, Kei, Zhao, Ming, Kiyuna, Tasuku, Miyake, Kentaro, Miyake, Masuyo, Nelson, Scott D., Dry, Sarah M., Li, Yunfeng, Yamamoto, Norio, Hayashi, Katsuhiro, Kimura, Hiroaki, Miwa, Shinji, Higuchi, Takashi, Singh, Shree Ram, Tsuchiya, Hiroyuki, Hoffman, Robert M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940643/
https://www.ncbi.nlm.nih.gov/pubmed/31896528
http://dx.doi.org/10.1016/j.tranon.2019.10.005
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author Igarashi, Kentaro
Kawaguchi, Kei
Zhao, Ming
Kiyuna, Tasuku
Miyake, Kentaro
Miyake, Masuyo
Nelson, Scott D.
Dry, Sarah M.
Li, Yunfeng
Yamamoto, Norio
Hayashi, Katsuhiro
Kimura, Hiroaki
Miwa, Shinji
Higuchi, Takashi
Singh, Shree Ram
Tsuchiya, Hiroyuki
Hoffman, Robert M.
author_facet Igarashi, Kentaro
Kawaguchi, Kei
Zhao, Ming
Kiyuna, Tasuku
Miyake, Kentaro
Miyake, Masuyo
Nelson, Scott D.
Dry, Sarah M.
Li, Yunfeng
Yamamoto, Norio
Hayashi, Katsuhiro
Kimura, Hiroaki
Miwa, Shinji
Higuchi, Takashi
Singh, Shree Ram
Tsuchiya, Hiroyuki
Hoffman, Robert M.
author_sort Igarashi, Kentaro
collection PubMed
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 IC(50) 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.
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spelling pubmed-69406432020-01-06 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 Igarashi, Kentaro Kawaguchi, Kei Zhao, Ming Kiyuna, Tasuku Miyake, Kentaro Miyake, Masuyo Nelson, Scott D. Dry, Sarah M. Li, Yunfeng Yamamoto, Norio Hayashi, Katsuhiro Kimura, Hiroaki Miwa, Shinji Higuchi, Takashi Singh, Shree Ram Tsuchiya, Hiroyuki Hoffman, Robert M. Transl Oncol Original article 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 IC(50) 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. Neoplasia Press 2019-12-30 /pmc/articles/PMC6940643/ /pubmed/31896528 http://dx.doi.org/10.1016/j.tranon.2019.10.005 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Igarashi, Kentaro
Kawaguchi, Kei
Zhao, Ming
Kiyuna, Tasuku
Miyake, Kentaro
Miyake, Masuyo
Nelson, Scott D.
Dry, Sarah M.
Li, Yunfeng
Yamamoto, Norio
Hayashi, Katsuhiro
Kimura, Hiroaki
Miwa, Shinji
Higuchi, Takashi
Singh, Shree Ram
Tsuchiya, Hiroyuki
Hoffman, Robert M.
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 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_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_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
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940643/
https://www.ncbi.nlm.nih.gov/pubmed/31896528
http://dx.doi.org/10.1016/j.tranon.2019.10.005
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