Kentaro Igarashi1,2,3, Kei Kawaguchi1,2, Norio Yamamoto3, Katsuhiro Hayashi3, Hiroaki Kimura3, Shinji Miwa3, Takashi Higuchi3, Yuta Taniguchi3, Hirotaka Yonezawa3, Yoshihiro Araki3, Sei Morinaga3, Sweta Misra4, Scott D Nelson5, Sarah M Dry5, Yunfeng Li5, Akira Odani6, Shree Ram Singh7, Hiroyuki Tsuchiya8, Robert M Hoffman9,2. 1. AntiCancer, Inc., San Diego, CA, U.S.A. 2. Department of Surgery, University of California, San Diego, CA, U.S.A. 3. Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan. 4. Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD, U.S.A. 5. Department of Pathology, University of California, Los Angeles, CA, U.S.A. 6. Division of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan. 7. Basic Research Laboratory, National Cancer Institute, Frederick, MD, U.S.A. all@anticancer.com singhshr@mail.nih.gov tsuchi@med.kanazawa-u.ac.jp. 8. Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan all@anticancer.com singhshr@mail.nih.gov tsuchi@med.kanazawa-u.ac.jp. 9. AntiCancer, Inc., San Diego, CA, U.S.A. all@anticancer.com singhshr@mail.nih.gov tsuchi@med.kanazawa-u.ac.jp.
Abstract
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. Copyright
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 osteosarcomapatient-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 patienttumor. 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. Copyright
Authors: G Bacci; S Ferrari; S Lari; M Mercuri; D Donati; A Longhi; C Forni; F Bertoni; M Versari; E Pignotti Journal: J Bone Joint Surg Br Date: 2002-01
Authors: Kentaro Igarashi; Kei Kawaguchi; Tasuku Kiyuna; Kentaro Miyake; Masuyo Miyake; Shukuan Li; Qinghong Han; Yuying Tan; Ming Zhao; Yunfeng Li; Scott D Nelson; Sarah M Dry; Arun S Singh; Irmina A Elliott; Tara A Russell; Mark A Eckardt; Norio Yamamoto; Katsuhiro Hayashi; Hiroaki Kimura; Shinji Miwa; Hiroyuki Tsuchiya; Fritz C Eilber; Robert M Hoffman Journal: Cell Cycle Date: 2018-04-10 Impact factor: 4.534
Authors: 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; Robert M Hoffman Journal: Oncotarget Date: 2017-06-28