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The combination of oral-recombinant methioninase and azacitidine arrests a chemotherapy-resistant osteosarcoma patient-derived orthotopic xenograft mouse model

  1. Author:
    Higuchi, Takashi
    Sugisawa, Norihiko
    Yamamoto, Jun
    Oshiro, Hiromichi
    Han, Qinghong
    Yamamoto, Norio
    Hayashi, Katsuhiro
    Kimura, Hiroaki
    Miwa, Shinji
    Igarashi, Kentaro
    Tan, Yuying
    Kuchipudi, Shreya
    Bouvet, Michael
    Singh,Shree Ram [ORCID]
    Tsuchiya, Hiroyuki
    Hoffman, Robert M

  2. Author Address

    AntiCancer, Inc, 7917 Ostrow Street, San Diego, CA, 92111, USA., Department of Surgery, University of California, San Diego, CA, USA., Department of Orthopedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan., Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA., Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, USA. singhshr@mail.nih.gov., Department of Orthopedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan. tsuchi@med.kanazawa-u.ac.jp., AntiCancer, Inc, 7917 Ostrow Street, San Diego, CA, 92111, USA. all@anticancer.com., Department of Surgery, University of California, San Diego, CA, USA. all@anticancer.com.,
    1. Year: 2019
    2. Date: Nov 08
    3. Epub Date: 2019 11 08
  2. Journal: Cancer chemotherapy and pharmacology
  4. Type of Article: Article
  5. ISSN: 0344-5704
  1. Abstract:

    PURPOSE: Cancers are methionine (MET) and methylation addicted, causing them to be highly sensitive to MET restriction. The present study determined the efficacy of restricting MET with oral-recombinant methioninase (o-rMETase) and the DNA methylation inhibitor, azacitidine (AZA) on a chemotherapy-resistant osteosarcoma patient-derived orthotopic xenograft (PDOX) mouse model. METHODS: The osteosarcoma PDOX models were randomized into five treatment groups of six mice: control; doxorubicin (DOX) alone; AZA alone; o-rMETase alone; o-rMETase-AZA combination. Tumor size and body weight were measured during the 14 days of treatment. RESULTS: We found that tumor growth was arrested only by the o-rMETase-AZA combination treatment, as tumors with this treatment exhibited tumor necrosis with degenerative change. CONCLUSION: This study suggests that o-rMETase-AZA combination has clinical potential for patients with chemoresistant osteosarcoma.

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External Sources

  1. View Full Text
  2. DOI: 10.1007/s00280-019-03986-0
  3. PMID: 31705268
  4. View record in Web of Science®
  5. WOS: 000495208700001
  6. PII : 10.1007/s00280-019-03986-0

Library Notes

  1. Fiscal Year: FY2019-2020
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