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.