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

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

研究成果: Article査読

26 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)285-291
ページ数7
ジャーナルCancer Chemotherapy and Pharmacology
85
2
DOI
出版ステータスPublished - 2020 2月 1
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学
  • 毒物学
  • 薬理学
  • 癌研究
  • 薬理学(医学)

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