Recombinant methioninase combined with doxorubicin (DOX) regresses a DOX-resistant synovial sarcoma in a patient-derived orthotopic xenograft (PDOX) mouse model

Kentaro Igarashi, Kei Kawaguchi, Shukuan Li, Qinghong Han, Yuying Tan, Emily Gainor, Tasuku Kiyuna, Kentaro Miyake, Masuyo Miyake, Takashi Higuchi, Hiromichi Oshiro, Arun S. Singh, Mark A. Eckardt, Scott D. Nelson, Tara A. Russell, Sarah M. Dry, Yunfeng Li, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki KimuraShinji Miwa, Hiroyuki Tsuchiya, Fritz C. Eilber, Robert M. Hoffman

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Synovial sarcoma (SS) is a recalcitrant subgroup of soft tissue sarcoma (STS). A tumor from a patient with high grade SS from a lower extremity was grown orthotopically in the right biceps femoris muscle of nude mice to establish a patientderived orthotopic xenograft (PDOX) mouse model. The PDOX mice were randomized into the following groups when tumor volume reached approximately 100 mm3: G1, control without treatment; G2, doxorubicin (DOX) (3 mg/kg, intraperitoneal [i.p.] injection, weekly, for 2 weeks; G3, rMETase (100 unit/mouse, i.p., daily, for 2 weeks); G4 DOX (3mg/kg), i.p. weekly, for 2 weeks) combined with rMETase (100 unit/ mouse, i.p., daily, for 2 weeks). On day 14 after treatment initiation, all therapies significantly inhibited tumor growth compared to untreated control, except DOX: (DOX: p = 0.48; rMETase: p < 0.005; DOX combined with rMETase < 0.0001). DOX combined with rMETase was significantly more effective than both DOX alone (p < 0.001) and rMETase alone (p < 0.05). The relative body weight on day 14 compared with day 0 did not significantly differ between any treatment group or untreated control. The results indicate that r-METase can overcome DOX-resistance in this recalcitrant disease.

Original languageEnglish
Pages (from-to)19263-19272
Number of pages10
JournalOncotarget
Volume9
Issue number27
DOIs
Publication statusPublished - 2018 Apr 10

Keywords

  • Doxorubicin
  • PDOX
  • Patient-derived orthotopic xenograft
  • Recombinant methioninase
  • Synovial sarcoma

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Recombinant methioninase combined with doxorubicin (DOX) regresses a DOX-resistant synovial sarcoma in a patient-derived orthotopic xenograft (PDOX) mouse model'. Together they form a unique fingerprint.

  • Cite this

    Igarashi, K., Kawaguchi, K., Li, S., Han, Q., Tan, Y., Gainor, E., Kiyuna, T., Miyake, K., Miyake, M., Higuchi, T., Oshiro, H., Singh, A. S., Eckardt, M. A., Nelson, S. D., Russell, T. A., Dry, S. M., Li, Y., Yamamoto, N., Hayashi, K., ... Hoffman, R. M. (2018). Recombinant methioninase combined with doxorubicin (DOX) regresses a DOX-resistant synovial sarcoma in a patient-derived orthotopic xenograft (PDOX) mouse model. Oncotarget, 9(27), 19263-19272. https://doi.org/10.18632/oncotarget.24996