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

作者: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*
来源:Oncotarget, 2017, 8(38): 63353-63359.
DOI:10.18632/oncotarget.18806

摘要

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 mm(3); CDDP (G2): 841.8 +/- 3 mm(3), p=0.0001; DOX (G3): 693.1 +/- 3 mm(3), p=6.56E-7; 3Pt (G4): 333.7 +/- 1 mm(3), 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.

  • 出版日期2017-9-8