PT - JOURNAL ARTICLE AU - IGARASHI, KENTARO AU - KAWAGUCHI, KEI AU - YAMAMOTO, NORIO AU - HAYASHI, KATSUHIRO AU - KIMURA, HIROAKI AU - MIWA, SHINJI AU - HIGUCHI, TAKASHI AU - TANIGUCHI, YUTA AU - YONEZAWA, HIROTAKA AU - ARAKI, YOSHIHIRO AU - MORINAGA, SEI AU - MISRA, SWETA AU - NELSON, SCOTT D. AU - DRY, SARAH M. AU - LI, YUNFENG AU - ODANI, AKIRA AU - SINGH, SHREE RAM AU - TSUCHIYA, HIROYUKI AU - HOFFMAN, ROBERT M. TI - A Novel Anionic-phosphate-platinum Complex Effectively Targets a Cisplatinum-resistant Osteosarcoma in a Patient-derived Orthotopic Xenograft Mouse Model AID - 10.21873/cgp.20182 DP - 2020 May 01 TA - Cancer Genomics - Proteomics PG - 217--223 VI - 17 IP - 3 4099 - http://cgp.iiarjournals.org/content/17/3/217.short 4100 - http://cgp.iiarjournals.org/content/17/3/217.full SO - Cancer Genomics Proteomics2020 May 01; 17 AB - Background/Aim: We have previously developed a novel bone-targeting platinum compound, 3Pt, and showed that it has strong inhibitory activity against osteosarcoma cells and orthotopic cell-line xenograft mouse models. In the present report, we compared the efficacy of 3Pt to cisplatinum (CDDP) in a CDDP-resistant relapsed osteosarcoma patient-derived orthotopic xenograft (PDOX) mouse model. Patients and Methods: The tumor of a patient with osteosarcoma of the distal femur was treated with CDDP-based chemotherapy followed by surgery. The surgical specimen was used to establish a PDOX model. An osteosarcoma cell line was also established from the original patient tumor. Osteosarcoma cell viability was assessed with the WST-8 assay and the IC50 values were calculated. The PDOX models were randomized into three groups: untreated control, CDDP-treated group, and 3Pt-treated group. Tumor size and body weight were measured twice a week. Results: 3Pt had a strong concentration-dependent cytocidal effect in vitro. The IC50 value of 3Pt was significantly lower than that of CDDP. On day 14 of the treatment, 3Pt caused a significantly greater tumor growth inhibition compared to the untreated control and CDDP-treated mice. Conclusion: 3Pt is a promising clinical candidate for the treatment of recalcitrant osteosarcoma.