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Recombinant Methioninase Combined With Tumor-targeting Salmonella typhimurium A1-R Induced Regression in a PDOX Mouse Model of Doxorubicin-resistant Dedifferentiated Liposarcoma

  1. Author:
    Igarashi, Kentaro
    Kawaguchi, Kei
    Zhao, Ming
    Han, Qinghong
    Tan, Yuying
    Kiyuna, Tasuku
    Miyake, Kentaro
    Higuchi, Takashi
    Nelson, Scott D
    Dry, Sarah M
    Li, Yunfeng
    Yamamoto, Norio
    Hayashi, Katsuhiro
    Kimura, Hiroaki
    Miwa, Shinji
    Singh,Shree Ram
    Tsuchiya, Hiroyuki
    Hoffman, Robert M

  2. Author Address

    AntiCancer, Inc., San Diego, CA, U.S.A., Department of Surgery, University of California, San Diego, CA, U.S.A., Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan., Department of Pathology, University of California, Los Angeles, CA, U.S.A., Basic Research Laboratory, National Cancer Institute, Frederick, MD, U.S.A. all@anticancer.com tsuchi@med.kanazawa-u.ac.jp singhshr@mail.nih.gov., Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan all@anticancer.com tsuchi@med.kanazawa-u.ac.jp singhshr@mail.nih.gov., AntiCancer, Inc., San Diego, CA, U.S.A. all@anticancer.com tsuchi@med.kanazawa-u.ac.jp singhshr@mail.nih.gov.,
    1. Year: 2020
    2. Date: May
  2. Journal: Anticancer research
    1. 40
    2. 5
    3. Pages: 2515-2523
  4. Type of Article: Article
  1. Abstract:

    Dedifferentiated liposarcoma (DDLPS) is associated with a poor survival rate even with multi-modality treatment. In the present study, we evaluated the efficacy of recombinant methioninase (rMETase) combined with tumor-targeting Salmonella typhimurium (S. typhimurium) A1-R against a doxorubicin-resistant DDLPS in a patient-derived orthotopic xenograft (PDOX) mouse model. A recurrent high-grade DDLPS from the right retroperitoneum of a patient was grown orthotopically in the retroperitoneum of nude mice to establish a PDOX model. The PDOX models were randomly divided into the following groups: Control, no treatment; doxorubicin monotherapy; rMETase monotherapy; S. typhimurium A1-R monotherapy; S. typhimurium A1-R and rMETase combination therapy. Tumor length and width were measured before and after treatment. On day 14 after treatment, all treatments significantly inhibited DDLPS PDOX tumor growth compared to the untreated control except for doxorubicin monotherapy. rMETase combined with S. typhimurium A1-R was significantly more effective and regressed tumor volume compared to either rMETase or S. typhimurium A1-R alone. The relative body weight did not significantly differ between days 0 and 14 for individual groups. The combination of rMETase and S. typhimurium A1-R has important clinical potential for this recalcitrant sarcoma. Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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External Sources

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  2. DOI: 10.21873/anticanres.14222
  3. PMID: 32366396
  4. PII : 40/5/2515

Library Notes

  1. Fiscal Year: FY2019-2020
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