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

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4653-4657
Number of pages5
JournalAnticancer research
Volume39
Issue number9
DOIs
Publication statusPublished - 2019
Externally publishedYes

Keywords

  • CDDP
  • Caffeine
  • O-rMETase
  • Osteosarcoma
  • PDOX
  • Regression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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