Research Papers:

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

Kentaro Igarashi, Kei Kawaguchi, Takashi Murakami, Tasuku Kiyuna, Kentaro Miyake, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Scott D. Nelson, Sarah M. Dry, Yunfeng Li, Arun S. Singh, Shinji Miwa, Akira Odani, Fritz C. Eilber, Hiroyuki Tsuchiya and Robert M. Hoffman _

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Oncotarget. 2017; 8:63353-63359. https://doi.org/10.18632/oncotarget.18806

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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

Correspondence to:

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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