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Research ArticleExperimental Studies

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

TAKASHI HIGUCHI, HIROMICHI OSHIRO, KENTARO MIYAKE, NORIHIKO SUGISAWA, QINGHONG HAN, YUYING TAN, JUNHO PARK, ZHIYING ZHANG, SAHAR RAZMJOOEI, NORIO YAMAMOTO, KATSUHIRO HAYASHI, HIROAKI KIMURA, SHINJI MIWA, KENTARO IGARASHI, MICHAEL BOUVET, SANT P. CHAWLA, SHREE RAM SINGH, HIROYUKI TSUCHIYA and ROBERT M. HOFFMAN
Anticancer Research September 2019, 39 (9) 4653-4657; DOI: https://doi.org/10.21873/anticanres.13646
TAKASHI HIGUCHI
1AntiCancer, Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California, San Diego, CA, U.S.A.
3Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
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HIROMICHI OSHIRO
1AntiCancer, Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California, San Diego, CA, U.S.A.
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KENTARO MIYAKE
1AntiCancer, Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California, San Diego, CA, U.S.A.
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NORIHIKO SUGISAWA
1AntiCancer, Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California, San Diego, CA, U.S.A.
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QINGHONG HAN
1AntiCancer, Inc., San Diego, CA, U.S.A.
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YUYING TAN
1AntiCancer, Inc., San Diego, CA, U.S.A.
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JUNHO PARK
1AntiCancer, Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California, San Diego, CA, U.S.A.
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ZHIYING ZHANG
1AntiCancer, Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California, San Diego, CA, U.S.A.
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SAHAR RAZMJOOEI
1AntiCancer, Inc., San Diego, CA, U.S.A.
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NORIO YAMAMOTO
3Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
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KATSUHIRO HAYASHI
3Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
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HIROAKI KIMURA
3Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
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SHINJI MIWA
3Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
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KENTARO IGARASHI
3Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
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MICHAEL BOUVET
2Department of Surgery, University of California, San Diego, CA, U.S.A.
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SANT P. CHAWLA
4Sarcoma Oncology Center, Santa Monica, CA, U.S.A.
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SHREE RAM SINGH
5Basic Research Laboratory, National Cancer Institute, Frederick, MD, U.S.A.
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  • For correspondence: all@anticancer.com tsuchi@med.kanazawa-u.ac.jp singhshr@mail.nih.gov
HIROYUKI TSUCHIYA
3Department of Orthopedic Surgery, Kanazawa University, Kanazawa, Japan
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  • For correspondence: all@anticancer.com tsuchi@med.kanazawa-u.ac.jp singhshr@mail.nih.gov
ROBERT M. HOFFMAN
1AntiCancer, Inc., San Diego, CA, U.S.A.
2Department of Surgery, University of California, San Diego, CA, U.S.A.
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  • For correspondence: all@anticancer.com tsuchi@med.kanazawa-u.ac.jp singhshr@mail.nih.gov
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Abstract

Background/Aim: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.

  • Osteosarcoma
  • PDOX
  • o-rMETase
  • caffeine
  • CDDP
  • regression
  • Received July 1, 2019.
  • Revision received July 9, 2019.
  • Accepted July 10, 2019.
  • Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
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Anticancer Research: 39 (9)
Anticancer Research
Vol. 39, Issue 9
September 2019
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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
TAKASHI HIGUCHI, HIROMICHI OSHIRO, KENTARO MIYAKE, NORIHIKO SUGISAWA, QINGHONG HAN, YUYING TAN, JUNHO PARK, ZHIYING ZHANG, SAHAR RAZMJOOEI, NORIO YAMAMOTO, KATSUHIRO HAYASHI, HIROAKI KIMURA, SHINJI MIWA, KENTARO IGARASHI, MICHAEL BOUVET, SANT P. CHAWLA, SHREE RAM SINGH, HIROYUKI TSUCHIYA, ROBERT M. HOFFMAN
Anticancer Research Sep 2019, 39 (9) 4653-4657; DOI: 10.21873/anticanres.13646

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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
TAKASHI HIGUCHI, HIROMICHI OSHIRO, KENTARO MIYAKE, NORIHIKO SUGISAWA, QINGHONG HAN, YUYING TAN, JUNHO PARK, ZHIYING ZHANG, SAHAR RAZMJOOEI, NORIO YAMAMOTO, KATSUHIRO HAYASHI, HIROAKI KIMURA, SHINJI MIWA, KENTARO IGARASHI, MICHAEL BOUVET, SANT P. CHAWLA, SHREE RAM SINGH, HIROYUKI TSUCHIYA, ROBERT M. HOFFMAN
Anticancer Research Sep 2019, 39 (9) 4653-4657; DOI: 10.21873/anticanres.13646
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Keywords

  • Osteosarcoma
  • PDOX
  • o-rMETase
  • caffeine
  • CDDP
  • regression
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