TY - JOUR T1 - A Novel Anionic-phosphate-platinum Complex Effectively Targets a Cisplatinum-resistant Osteosarcoma in a Patient-derived Orthotopic Xenograft Mouse Model JF - Cancer Genomics - Proteomics JO - Cancer Genomics Proteomics SP - 217 LP - 223 DO - 10.21873/cgp.20182 VL - 17 IS - 3 AU - KENTARO IGARASHI AU - KEI KAWAGUCHI AU - NORIO YAMAMOTO AU - KATSUHIRO HAYASHI AU - HIROAKI KIMURA AU - SHINJI MIWA AU - TAKASHI HIGUCHI AU - YUTA TANIGUCHI AU - HIROTAKA YONEZAWA AU - YOSHIHIRO ARAKI AU - SEI MORINAGA AU - SWETA MISRA AU - SCOTT D. NELSON AU - SARAH M. DRY AU - YUNFENG LI AU - AKIRA ODANI AU - SHREE RAM SINGH AU - HIROYUKI TSUCHIYA AU - ROBERT M. HOFFMAN Y1 - 2020/05/01 UR - http://cgp.iiarjournals.org/content/17/3/217.abstract N2 - 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. ER -