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The combination of olaratumab with gemcitabine and docetaxel arrests a chemotherapy-resistant undifferentiated soft-tissue sarcoma in a patient-derived orthotopic xenograft mouse model

  1. Author:
    Higuchi, Takashi
    Miyake, Kentaro
    Sugisawa, Norihiko
    Oshiro, Hiromichi
    Zhang, Zhiying
    Razmjooei, Sahar
    Yamamoto, Norio
    Hayashi, Katsuhiro
    Kimura, Hiroaki
    Miwa, Shinji
    Igarashi, Kentaro
    Bouvet, Michael
    Singh,Shree Ram
    Tsuchiya, Hiroyuki
    Hoffman, Robert M.

  2. Author Address

    AntiCancer Inc, San Diego, CA 92111 USA.Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA.Kanazawa Univ, Dept Orthoped Surg, Kanazawa, Ishikawa, Japan.NCI, Basic Res Lab, Frederick, MD 21701 USA.
    1. Year: 2019
    2. Date: Jun
    3. Epub Date: 2019 03 30
  2. Journal: CANCER CHEMOTHERAPY AND PHARMACOLOGY
  3. SPRINGER,
    1. 83
    2. 6
    3. Pages: 1075-1082
  5. Type of Article: Article
  6. ISSN: 0344-5704
  1. Abstract:

    PurposeOlaratumab (OLA) is a monoclonal antibody against platelet-derived growth factor receptor alpha. OLA has recently been used against soft-tissue sarcoma (STS) combined with doxorubicin (DOX), but with limited efficacy. The goal of present study was to determine the efficacy of OLA combined with gemcitabine (GEM) and docetaxel (DOC) on a chemotherapy-resistant STS patient-derived orthotopic xenograft (PDOX).MethodsUndifferentiated 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 the PDOX model. The USTS PDOX was treated with GEM alone, GEM combined with DOC, OLA combined with DOX or GEM, and OLA combined with GEM and DOC. Tumor size and body weight were measured during the 14days of treatment.ResultsTumor growth was arrested only by OLA combined with GEM and DOC. Tumors treated with OLA combined with GEM and DOC also had the most necrosis.ConclusionsThe present study demonstrates the power of the PDOX model to identify the novel effective treatment strategy of the combination of OLA, GEM and DOC for drug-resistant soft-tissue sarcoma.

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External Sources

  1. View Full Text
  2. DOI: 10.1007/s00280-019-03824-3
  3. PMID: 30929053
  4. View record in Web of Science®
  5. WOS: 000467025300008

Library Notes

  1. Fiscal Year: FY2018-2019
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