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Combination of oral recombinant methioninase and decitabine arrests a chemotherapy-resistant undifferentiated soft-tissue sarcoma patient-derived orthotopic xenograft mouse model

  1. Author:
    Higuchi, Takashi
    Han, Qinghong
    Miyake, Kentaro
    Oshiro, Hiromichi
    Sugisawa, Norihiko
    Tan, Yuying
    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, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan., AntiCancer, Inc., San Diego, CA, USA., AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA., Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA. Electronic address: singhshr@mail.nih.gov., Department of Orthopedic 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: 2020
    2. Date: FEB 26
    3. Epub Date: 2019 12 12
  2. Journal: Biochemical and biophysical research communications
    1. 523
    2. 1
    3. Pages: 135-139
  4. Type of Article: Article
  5. ISSN: 0006-291X
  1. Abstract:

    Cancer cells are methionine (MET) and methylation addicted and are highly sensitive to MET restriction. The present study determined the efficacy of oral-recombinant methioninase (o-rMETase) and the DNA methylation inhibitor, decitabine (DAC) on restricting MET in an undifferentiated-soft tissue sarcoma (USTS) patient-derived orthotopic xenograft (PDOX) nude-mouse model. The USTS PDOX models were randomized into five treatment groups of six mice: Control; doxorubicin (DOX) alone; DAC alone; o-rMETase alone; and o-rMETase-DAC combination. Tumor size and body weight were measured during the 14 days of treatment. Tumor growth was arrested only in the o-rMETase-DAC condition. Tumors treated with the o-rMETase-DAC combination exhibited tumor necrosis with degenerative changes. This study demonstrates that the o-rMETase-DAC combination could arrest the USTS PDOX tumor suggesting clinical promise. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.bbrc.2019.12.024
  3. PMID: 31839218
  4. View record in Web of Science®
  5. WOS: 000524719500022
  6. PII : S0006-291X(19)32344-7

Library Notes

  1. Fiscal Year: FY2019-2020
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