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

  • Author(s): Igarashi, Kentaro;
  • Kawaguchi, Kei;
  • Murakami, Takashi;
  • Kiyuna, Tasuku;
  • Miyake, Kentaro;
  • Yamamoto, Norio;
  • Hayashi, Katsuhiro;
  • Kimura, Hiroaki;
  • Nelson, Scott D;
  • Dry, Sarah M;
  • Li, Yunfeng;
  • Singh, Arun S;
  • Miwa, Shinji;
  • Odani, Akira;
  • Eilber, Fritz C;
  • Tsuchiya, Hiroyuki;
  • Hoffman, Robert M
  • et al.
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) nude-mouse 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.

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