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Oral Recombinant Methioninase, Combined With Oral Caffeine and Injected Cisplatinum, Overcome Cisplatinum-Resistance and Regresses Patient-derived Orthotopic Xenograft Model of Osteosarcoma

  1. Author:
    Higuchi, Takashi
    Oshiro, Hiromichi
    Miyake, Kentaro
    Sugisawa, Norihiko
    Han, Qinghong
    Tan, Yuying
    Park, Junho
    Zhang, Zhiying
    Razmjooei, Sahar
    Yamamoto, Norio
    Hayashi, Katsuhiro
    Kimura, Hiroaki
    Miwa, Shinji
    Igarashi, Kentaro
    Bouvet, Michael
    Chawla, Sant P
    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 Orthopedic Surgery, Kanazawa University, Kanazawa, Japan., Sarcoma Oncology Center, Santa Monica, 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 Orthopedic 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: 2019
    2. Date: Sep
  2. Journal: Anticancer research
    1. 39
    2. 9
    3. Pages: 4653-4657
  4. Type of Article: Article
  5. ISSN: 0250-7005
  1. Abstract:

    Osteosarcoma is a recalcitrant neoplasm which occurs predominantly in adolescents and young adults. Recently, using a patient-derived orthotopic xenograft (PDOX) model of malignant soft-tissue sarcoma (STS), we showed that oral recombinant methioninase (o-rMETase), in combination with caffeine, was more efficacious than o-rMETase alone in inhibiting STS tumor growth. In the present report, we determined the efficacy of o-rMETase combined with oral caffeine on a cisplatinum (CDDP)-resistant osteosarcoma PDOX model. Osteosarcoma PDOX models were randomly divided into seven treatment groups (6 mice in each group): untreated control; CDDP alone; o-rMETase alone; o-rMETase with caffeine; CDDP plus o-rMETase; CDDP plus caffeine; and CDDP plus o-rMETase with caffeine. Tumor size and body weight were measured throughout the treatment. Tumors regressed after treatment with CDDP plus o-rMETase with caffeine. Tumors treated with CDDP plus o-rMETase with caffeine also had the most necrosis. The combination of o-rMETase and caffeine together with first-line chemotherapy was efficacious for drug-resistant osteosarcoma and has clinical potential in the treatment of this highly-resistant neoplasm. Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.21873/anticanres.13646
  3. PMID: 31519563
  4. View record in Web of Science®
  5. WOS: 000486457600009
  6. PII : 39/9/4653

Library Notes

  1. Fiscal Year: FY2019-2020

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