A novel anionic-phosphate-platinum complex effectively targets an undifferentiated pleomorphic sarcoma better than cisplatinum and doxorubicin in a patient-derived orthotopic xenograft (PDOX)

Kentaro Igarashi, Kei Kawaguchi, Takashi Murakami, Tasuku Kiyuna, Kentaro Miyake, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Scott D. Nelson, Sarah M. Dry, Yunfeng Li, Arun S. Singh, Shinji Miwa, Akira Odani, Fritz C. Eilber, Hiroyuki Tsuchiya, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

A patient high-grade undifferentiated pleomorphic soft-tissue sarcoma (UPS) from a striated muscle was previously orthotopically implanted in the right biceps femoris muscle of nude mice to establish a patient-derived orthotopic xenograft (PDOX) nudemouse model. In the present study, two weeks after orthotopic transplantation of the UPS, mice were treated intraperitoneally with cisplatinum (CDDP), doxorubicin (DOX) or a novel anionic-phosphate-platinum compound 3Pt. Treatments were repeated weekly for a total of 3 times. Six weeks after transplantation, all mice were sacrificed and evaluated. After two weeks treatment, tumor sizes were as follows: control (G1): 2208.3 mm3; CDDP (G2): 841.8±3 mm3, p=0.0001; DOX (G3): 693.1±3 mm3, p=6.56E-7; 3Pt (G4): 333.7±1 mm3, p=4.8E-8. 3Pt showed significantly more efficacy compared to other therapy drugs tested: CDDP (p=0.0002), DOX (p=0.001). There were no animal deaths in any of the four groups. The present results suggest 3Pt is a promising new candidate for UPS since it was demonstrated to be effective in a PDOX model.

Original languageEnglish
Pages (from-to)63353-63359
Number of pages7
JournalOncotarget
Volume8
Issue number38
DOIs
Publication statusPublished - 2017

Keywords

  • 3Pt
  • Efficacy
  • PDOX
  • Platinum complex
  • Undifferentiated pleomorphic sarcoma

ASJC Scopus subject areas

  • Oncology

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