Recombinant Methioninase Combined With Tumor-targeting Salmonella typhimurium A1-R Induced Regression in a PDOX Mouse Model of Doxorubicin-resistant Dedifferentiated Liposarcoma.

Abstract

BACKGROUND/AIM:

Dedifferentiated liposarcoma (DDLPS) is associated with a poor survival rate even with multi-modality 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.

• Authors: 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
• Journal: Anticancer research (Anticancer Res) Vol. 40 Issue 5 Pg. 2515-2523 (May 2020) ISSN: 1791-7530 [Electronic] Greece
• PMID: 32366396 (Publication Type: Journal Article)
• Copyright: Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Antimetabolites, Antineoplastic
• Recombinant Proteins
• Doxorubicin
• Carbon-Sulfur Lyases
• L-methionine gamma-lyase

Topics

• Animals
• Antimetabolites, Antineoplastic (pharmacology)
• Carbon-Sulfur Lyases (pharmacology)
• Combined Modality Therapy
• Disease Models, Animal
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm (drug effects)
• Humans
• Immunohistochemistry
• Liposarcoma (drug therapy, pathology)
• Mice
• Recombinant Proteins (pharmacology)
• Salmonella typhimurium (physiology)
• Xenograft Model Antitumor Assays