Статья

The Combination of Olaratumab with Doxorubicin and Cisplatinum Regresses a Chemotherapy-Resistant Osteosarcoma in a Patient-Derived Orthotopic Xenograft Mouse Model

Takashi HiguchiAntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Orthopedic Surgery, Kanazawa University, Kanazawa, JapanNorihiko SugisawaAntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USAKentaro MiyakeAntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USAHiromichi OshiroAntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USANorio YamamotoDepartment of Orthopedic Surgery, Kanazawa University, Kanazawa, JapanKatsuhiro HayashiDepartment of Orthopedic Surgery, Kanazawa University, Kanazawa, JapanHiroaki KimuraDepartment of Orthopedic Surgery, Kanazawa University, Kanazawa, JapanShinji MiwaDepartment of Orthopedic Surgery, Kanazawa University, Kanazawa, JapanKentaro IgarashiDepartment of Orthopedic Surgery, Kanazawa University, Kanazawa, JapanMichael BouvetDepartment of Surgery, University of California, San Diego, CA, USAShree Ram SinghBasic Research Laboratory, National Cancer Institute, Frederick, MD, USA. Electronic address: [email protected]Hiroyuki TsuchiyaDepartment of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan. Electronic address: [email protected]Robert M. HoffmanAntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA. Electronic address: [email protected]

2019en

ABI

Аннотация

Chemotherapy-resistant osteosarcoma is a recalcitrant disease. It is a frequent cause of death to the patients who are usually adolescent or young adults. The goal of the present study was to determine the efficacy of the combination of olaratumab (OLA), doxorubicin (DOX), and cisplatinum (CDDP) on osteosarcoma, which is resistant to first-line therapy, in a patient-derived orthotopic xenograft (PDOX) model. The osteosarcoma PDOX model was randomized into six treatment groups of six mice: control; CDDP alone; DOX and CDDP; OLA + DOX; OLA + CDDP; and OLA + DOX and CDDP. Tumor size and body weight were measured during 14 days of treatment. Tumor growth was regressed only by the treatment with a combination of OLA + DOX and CDDP. Tumors treated with this three-drug combination had the most tumor necrosis and the lowest Ki-67 index. The present study demonstrates the power of the PDOX model to identify novel effective treatment strategy for chemotherapy-resistant osteosarcoma.

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Идентификаторы

DOI: 10.1016/j.tranon.2019.06.002

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar