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Pazopanib regresses a doxorubicin-resistant synovial sarcoma in a patient-derived orthotopic xenograft mouse model

  1. Author:
    Igarashi, Kentaro
    Kawaguchi, Kei
    Kiyuna, Tasuku
    Miyake, Kentaro
    Miyake, Masuyo
    Nelson, Scott D
    Russell, Tara A
    Dry, Sarah M
    Li, Yunfeng
    Yamamoto, Norio
    Hayashi, Katsuhiro
    Kimura, Hiroaki
    Miwa, Shinji
    Higuchi, Takashi
    Singh,Shree Ram
    Tsuchiya, Hiroyuki
    Hoffman, Robert M

  2. Author Address

    AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan., AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA., Department of Pathology, University of California, Los Angeles, CA, USA., Division of Surgical Oncology, University of California, Los Angeles, CA, USA., Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA. Electronic address: singhshr@mail.nih.gov., Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan. Electronic address: tsuchi@med.kanazawa-u.ac.jp., AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA. Electronic address: all@anticancer.com.,
    1. Year: 2019
    2. Date: Jun
    3. Epub Date: 2019 05 03
  2. Journal: Tissue & cell
    1. 58
    2. Pages: 107-111
  4. Type of Article: Article
  1. Abstract:

    Synovial sarcoma (SS) is an aggressive subgroup of soft tissue sarcoma (STS) with high grade and high risk of metastasis. However, there are no systemic therapies available that target SS. Therefore, transformative therapy is needed for SS. To establish a patient-derived orthotopic xenograft (PDOX) model, a patient tumor with high grade SS from a lower extremity was grown orthotopically in the right biceps femoris muscle of mice. To test the efficacy of drugs, the PDOX models were randomized into five groups: Group 1 (G1), control-without treatment; Group 2 (G2), doxorubicin (DOX); Group 3 (G3), temozolomide (TEM); Group 4 (G4), gemcitabine (GEM) combined with docetaxel (DOC); and Group 5 (G5), pazopanib (PAZ). Tumor size and body weight were measured twice a week for each treatment group. A significant growth inhibition was found on day 14 in each treatment group compared to the untreated control, except for DOX. However, PAZ was significantly more effective than both TEM and GEM?+?DOC. In addition, PAZ significantly regressed the tumor volume on day 14 compared to day 0. No change was found in body weight on day 14 compared to day 0 in any treatment group. The present study demonstrated the precision of the SS PDOX models for individualizing SS therapy. Published by Elsevier Ltd.

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External Sources

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  2. DOI: 10.1016/j.tice.2019.04.010
  3. PMID: 31133237
  4. PII : S0040-8166(19)30147-8

Library Notes

  1. Fiscal Year: FY2018-2019
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