Olaratumab combined with doxorubicin and ifosfamide overcomes individual doxorubicin and olaratumab resistance of an undifferentiated soft-tissue sarcoma in a PDOX mouse model
| Autor: | Norihiko Sugisawa, Kentaro Miyake, Katsuhiro Hayashi, Hiroaki Kimura, Norio Yamamoto, Sahar Razmjooei, Shinji Miwa, Kentaro Igarashi, Takashi Higuchi, Robert M. Hoffman, Hiroyuki Tsuchiya, Hiromichi Oshiro, Zhiying Zhang, Shree Ram Singh, Michael Bouvet |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Necrosis Combination therapy medicine.drug_class macromolecular substances Monoclonal antibody Mice 03 medical and health sciences 0302 clinical medicine Growth factor receptor Antineoplastic Combined Chemotherapy Protocols polycyclic compounds medicine Animals Humans Doxorubicin Ifosfamide Chemistry organic chemicals technology industry and agriculture Antibodies Monoclonal Sarcoma medicine.disease Xenograft Model Antitumor Assays carbohydrates (lipids) Disease Models Animal 030104 developmental biology Oncology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research medicine.symptom Olaratumab medicine.drug |
| Zdroj: | Cancer Letters. 451:122-127 |
| ISSN: | 0304-3835 |
| Popis: | Olaratumab (OLA), a monoclonal antibody against platelet-derived growth factor receptor alpha (PDGFRα), has recently been used against soft-tissue sarcoma (STS) combined with doxorubicin (DOX), with limited efficacy. The goal of the present study was to determine the efficacy of OLA in combination with DOX and ifosfamide (IFO) on STS. Undifferentiated soft-tissue sarcoma (USTS) from a striated muscle of a patient was grown orthotopically in the right biceps femoris muscle of nude mice to establish USTS patient-derived orthotopic xenograft (PDOX) model. USTS PDOX tumors were treated with OLA alone, DOX alone, DOX combined with IFO, OLA combined with DOX or IFO, and OLA combined with DOX and IFO. Tumor size and body weight were measured during the 14 days of treatment. Tumor growth was arrested by OLA combined with DOX and IFO. Tumors treated with OLA combined with DOX and IFO had the most necrosis. The present study demonstrates the power of the PDOX model to identify the novel effective treatment strategy of the combination of OLA, DOX and IFO for soft-tissue sarcomas. |
| Databáze: | OpenAIRE |
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