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Trabectedin and irinotecan combination regresses a cisplatinum-resistant osteosarcoma in a patient-derived orthotopic xenograft nude-mouse model

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

  2. Author Address

    AntiCanc 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.Sarcoma Oncol Ctr, Santa Monica, CA USA.NCI, Basic Res Lab, Frederick, MD 21701 USA.
    1. Year: 2019
    2. Date: MAY 28
    3. Epub Date: 2019 04 04
  2. Journal: Biochemical and biophysical research communications
  3. ACADEMIC PRESS INC ELSEVIER SCIENCE,
    1. 513
    2. 2
    3. Pages: 326-331
  5. Type of Article: Article
  6. ISSN: 0006-291X
  1. Abstract:

    Recurrent osteosarcoma is a chemotherapy-resistant disease. Individualized precision therapy is needed for this disease. Toward this goal, we have developed the patient-derived othotopic xenograft (PDOX) mouse model of all major cancer types including osteosarcoma. Synergistic efficacy of trabectedin (TRAB) and irinotecan (IRT) has been reported in Ewing's sarcoma, soft-tissue sarcoma, and ovarian cancer. However, the efficacy of this combination on osteosarcoma is not known. The goal of present study was to determine the efficacy of the TRAB and IRT combination on cisplatinum (CDDP)-resistant osteosarcoma PDOX. The osteosarcoma PDOX models were randomized into five treatment groups of six mice: Untreated control; CDDP alone; TRAB alone; IRT alone; and TRAB and the IRT combination. Tumor size and body weight were measured during the 14 days of treatment. Tumor growth was regressed only by the TRAB-IRT combination. Tumors treated with the TRAB-IRT combination had the most tumor necrosis with degenerative change. The present study demonstrates the power of the PDOX model to identify a novel effective treatment strategy of the TRAB and IRT combination for chemotherapy-resistant osteosarcoma. Published by Elsevier Inc.

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External Sources

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  2. DOI: 10.1016/j.bbrc.2019.03.191
  3. PMID: 30955860
  4. View record in Web of Science®
  5. WOS: 000468258600006

Library Notes

  1. Fiscal Year: FY2018-2019
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