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A patient-derived orthotopic xenograft (PDOX) mouse model of a cisplatinum-resistant osteosarcoma lung metastasis that was sensitive to temozolomide and trabectedin: implications for precision oncology

In the present study, we evaluated the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared to cisplatinum (CDDP) on a patient-derived orthotopic xenogrraft (PDOX) of a lung-metastasis from an osteosarcoma of a patient who failed CDDP therapy. Osteosarcoma resected from the patient was imp...

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Autores principales: Igarashi, Kentaro, Murakami, Takashi, Kawaguchi, Kei, Kiyuna, Tasuku, Miyake, Kentaro, Zhang, Yong, Nelson, Scott D., Dry, Sarah M., Li, Yunfeng, Yanagawa, Jane, Russell, Tara A., Singh, Arun S., Tsuchiya, Hiroyuki, Elliott, Irmina, Eilber, Fritz C., Hoffman, Robert M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617490/
https://www.ncbi.nlm.nih.gov/pubmed/28977930
http://dx.doi.org/10.18632/oncotarget.19095
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author Igarashi, Kentaro
Murakami, Takashi
Kawaguchi, Kei
Kiyuna, Tasuku
Miyake, Kentaro
Zhang, Yong
Nelson, Scott D.
Dry, Sarah M.
Li, Yunfeng
Yanagawa, Jane
Russell, Tara A.
Singh, Arun S.
Tsuchiya, Hiroyuki
Elliott, Irmina
Eilber, Fritz C.
Hoffman, Robert M.
author_facet Igarashi, Kentaro
Murakami, Takashi
Kawaguchi, Kei
Kiyuna, Tasuku
Miyake, Kentaro
Zhang, Yong
Nelson, Scott D.
Dry, Sarah M.
Li, Yunfeng
Yanagawa, Jane
Russell, Tara A.
Singh, Arun S.
Tsuchiya, Hiroyuki
Elliott, Irmina
Eilber, Fritz C.
Hoffman, Robert M.
author_sort Igarashi, Kentaro
collection PubMed
description In the present study, we evaluated the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared to cisplatinum (CDDP) on a patient-derived orthotopic xenogrraft (PDOX) of a lung-metastasis from an osteosarcoma of a patient who failed CDDP therapy. Osteosarcoma resected from the patient was implanted orthotopically in the distal femur of mice to establish PDOX models which were randomized into the following groups when tumor volume reached approximately 100 mm(3): G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal injection, weekly, for 2 weeks); G3, TRAB (0.15 mg/kg, intravenous injection, weekly, for 2 weeks); G4, TEM (25 mg/kg, oral, daily, for 14 days). Tumor size and body weight were measured with calipers and a digital balance, respectively, twice a week. On day 14 after initiation of treatment, TEM and TRAB, but not CDDP, significantly inhibited tumor volume compared to untreated control: control (G1): 814.5±258.8 mm(3); CDDP (G2): 608.6±126.9 mm(3); TRAB (G3): 286.6±133.0 mm(3); TEM (G4): 182.9±69.1 mm(3). CDDP vs. control, p=0.07; TRAB vs. control, p=0.0004; TEM vs. control p =0.0002; TRAB vs. CDDP, p =0.0002; TEM vs. CDDP, p =0.00003. The results of the present study show that a PDOX model of an osteosarcoma lung-metastasis that recurred after adjuvant CDDP-treatment has identified potentially, highly-effective drugs for this recalcitrant disease, while accurately maintaining the CDDP resistance of the tumor in the patient, thereby demonstrating the potential of the osteosarcoma PDOX model for precision oncology.
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spelling pubmed-56174902017-10-03 A patient-derived orthotopic xenograft (PDOX) mouse model of a cisplatinum-resistant osteosarcoma lung metastasis that was sensitive to temozolomide and trabectedin: implications for precision oncology Igarashi, Kentaro Murakami, Takashi Kawaguchi, Kei Kiyuna, Tasuku Miyake, Kentaro Zhang, Yong Nelson, Scott D. Dry, Sarah M. Li, Yunfeng Yanagawa, Jane Russell, Tara A. Singh, Arun S. Tsuchiya, Hiroyuki Elliott, Irmina Eilber, Fritz C. Hoffman, Robert M. Oncotarget Research Paper In the present study, we evaluated the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared to cisplatinum (CDDP) on a patient-derived orthotopic xenogrraft (PDOX) of a lung-metastasis from an osteosarcoma of a patient who failed CDDP therapy. Osteosarcoma resected from the patient was implanted orthotopically in the distal femur of mice to establish PDOX models which were randomized into the following groups when tumor volume reached approximately 100 mm(3): G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal injection, weekly, for 2 weeks); G3, TRAB (0.15 mg/kg, intravenous injection, weekly, for 2 weeks); G4, TEM (25 mg/kg, oral, daily, for 14 days). Tumor size and body weight were measured with calipers and a digital balance, respectively, twice a week. On day 14 after initiation of treatment, TEM and TRAB, but not CDDP, significantly inhibited tumor volume compared to untreated control: control (G1): 814.5±258.8 mm(3); CDDP (G2): 608.6±126.9 mm(3); TRAB (G3): 286.6±133.0 mm(3); TEM (G4): 182.9±69.1 mm(3). CDDP vs. control, p=0.07; TRAB vs. control, p=0.0004; TEM vs. control p =0.0002; TRAB vs. CDDP, p =0.0002; TEM vs. CDDP, p =0.00003. The results of the present study show that a PDOX model of an osteosarcoma lung-metastasis that recurred after adjuvant CDDP-treatment has identified potentially, highly-effective drugs for this recalcitrant disease, while accurately maintaining the CDDP resistance of the tumor in the patient, thereby demonstrating the potential of the osteosarcoma PDOX model for precision oncology. Impact Journals LLC 2017-07-08 /pmc/articles/PMC5617490/ /pubmed/28977930 http://dx.doi.org/10.18632/oncotarget.19095 Text en Copyright: © 2017 Igarashi et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Igarashi, Kentaro
Murakami, Takashi
Kawaguchi, Kei
Kiyuna, Tasuku
Miyake, Kentaro
Zhang, Yong
Nelson, Scott D.
Dry, Sarah M.
Li, Yunfeng
Yanagawa, Jane
Russell, Tara A.
Singh, Arun S.
Tsuchiya, Hiroyuki
Elliott, Irmina
Eilber, Fritz C.
Hoffman, Robert M.
A patient-derived orthotopic xenograft (PDOX) mouse model of a cisplatinum-resistant osteosarcoma lung metastasis that was sensitive to temozolomide and trabectedin: implications for precision oncology
title A patient-derived orthotopic xenograft (PDOX) mouse model of a cisplatinum-resistant osteosarcoma lung metastasis that was sensitive to temozolomide and trabectedin: implications for precision oncology
title_full A patient-derived orthotopic xenograft (PDOX) mouse model of a cisplatinum-resistant osteosarcoma lung metastasis that was sensitive to temozolomide and trabectedin: implications for precision oncology
title_fullStr A patient-derived orthotopic xenograft (PDOX) mouse model of a cisplatinum-resistant osteosarcoma lung metastasis that was sensitive to temozolomide and trabectedin: implications for precision oncology
title_full_unstemmed A patient-derived orthotopic xenograft (PDOX) mouse model of a cisplatinum-resistant osteosarcoma lung metastasis that was sensitive to temozolomide and trabectedin: implications for precision oncology
title_short A patient-derived orthotopic xenograft (PDOX) mouse model of a cisplatinum-resistant osteosarcoma lung metastasis that was sensitive to temozolomide and trabectedin: implications for precision oncology
title_sort patient-derived orthotopic xenograft (pdox) mouse model of a cisplatinum-resistant osteosarcoma lung metastasis that was sensitive to temozolomide and trabectedin: implications for precision oncology
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617490/
https://www.ncbi.nlm.nih.gov/pubmed/28977930
http://dx.doi.org/10.18632/oncotarget.19095
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