Recombinant methioninase combined with tumor-targeting salmonella typhimurium a1-r induced regression in a PDOX mouse model of doxorubicin-resistant dedifferentiated liposarcoma

Kentaro Igarashi, Kei Kawaguchi, Ming Zhao, Qinghong Han, Yuying Tan, Tasuku Kiyuna, Kentaro Miyake, Takashi Higuchi, Scott D. Nelson, Sarah M. Dry, Yunfeng Li, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Shree Ram Singh, Hiroyuki Tsuchiya, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background/Aim: Dedifferentiated liposarcoma (DDLPS) is associated with a poor survival rate even with multimodality treatment. In the present study, we evaluated the efficacy of recombinant methioninase (rMETase) combined with tumor-targeting Salmonella typhimurium (S. typhimurium) A1- R against a doxorubicin-resistant DDLPS in a patient-derived orthotopic xenograft (PDOX) mouse model. Materials and Methods: A recurrent high-grade DDLPS from the right retroperitoneum of a patient was grown orthotopically in the retroperitoneum of nude mice to establish a PDOX model. The PDOX models were randomly divided into the following groups: Control, no treatment; doxorubicin monotherapy; rMETase monotherapy; S. typhimurium A1-R monotherapy; S. typhimurium A1-R and rMETase combination therapy. Tumor length and width were measured before and after treatment. Results: On day 14 after treatment, all treatments significantly inhibited DDLPS PDOX tumor growth compared to the untreated control except for doxorubicin monotherapy. rMETase combined with S. typhimurium A1-R was significantly more effective and regressed tumor volume compared to either rMETase or S. typhimurium A1-R alone. The relative body weight did not significantly differ between days 0 and 14 for individual groups. Conclusion: The combination of rMETase and S. typhimurium A1-R has important clinical potential for this recalcitrant sarcoma.

Original languageEnglish
Pages (from-to)2515-2523
Number of pages9
JournalAnticancer research
Volume40
Issue number5
DOIs
Publication statusPublished - 2020 May
Externally publishedYes

Keywords

  • Combination
  • Dedifferentiated liposarcoma
  • Nude mice
  • PDOX
  • Recombinant methioninase
  • S. typhimurium A1-R
  • Tumor regression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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