A novel anionic-phosphate-platinum complex effectively targets an undifferentiated pleomorphic sarcoma better than cisplatinum and doxorubicin in a patient-derived orthotopic xenograft (PDOX)
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Kentaro Igarashi1,2,3, Kei Kawaguchi1,2, Takashi Murakami1,2, Tasuku Kiyuna1,2, Kentaro Miyake1,2, Norio Yamamoto3, Katsuhiro Hayashi3, Hiroaki Kimura3, Scott D. Nelson4, Sarah M. Dry4, Yunfeng Li4, Arun S. Singh5, Shinji Miwa3, Akira Odani6, Fritz C. Eilber7, Hiroyuki Tsuchiya3 and Robert M. Hoffman1,2
1AntiCancer, Inc., San Diego, California, USA
2Department of Surgery, University of California, San Diego, California, USA
3Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan
4Department of Pathology, University of California, Los Angeles, California, USA
5Division of Hematology-Oncology, University of California, Los Angeles, California, USA
6Division of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan
7Division of Surgical Oncology, University of California, Los Angeles, California, USA
Robert M. Hoffman, email: [email protected]
Fritz C. Eilber, email: [email protected]
Hiroyuki Tsuchiya, email: [email protected]
Keywords: platinum complex, 3Pt, undifferentiated pleomorphic sarcoma, PDOX, efficacy
Received: April 25, 2017 Accepted: May 12, 2017 Published: June 28, 2017
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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