研究者詳細 - 國定　俊之

Hideo Morioka, Shunji Takahashi, Nobuhito Araki, Hideshi Sugiura, Takafumi Ueda, Mitsuru Takahashi, Tsukasa Yonemoto, Hiroaki Hiraga, Toru Hiruma, Toshiyuki Kunisada, Akihiko Matsumine, Michiro Susa, Robert Nakayama, Kazumasa Nishimoto, Kazutaka Kikuta, Keisuke Horiuchi, Akira Kawai

BMC CANCER 16 479 2016年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BIOMED CENTRAL LTD

Background: Trabectedin is reported to be particularly effective against translocation-related sarcoma. Recently, a randomized phase 2 study in patients with translocation-related sarcomas unresponsive or intolerable to standard chemotherapy was conducted, which showed clinical benefit of trabectedin compared with best supportive care (BSC). Extraskeletal myxoid chondrosarcoma (EMCS) and Mesenchymal chondrosarcoma (MCS) are very rare malignant soft tissue sarcomas, and are associated with translocations resulting in fusion genes. In addition, the previous in vivo data showed that trabectedin affect tumor necrosis and reduction in vascularization in a xenograft model of a human high-grade chondrosarcoma. The aim of the present analysis was to clarify the efficacy of trabectedin for EMCS and MCS subjects in the randomized phase 2 study.
Methods: Five subjects with EMCS and MCS received trabectedin treatment in the randomized phase 2 study. Three MCS subjects were allocated to the BSC group. Objective response and progression-free survival (PFS) were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by central radiology imaging review.
Results: The median follow-up time of the randomized phase 2 study was 22.7 months, and one subject with MCS was still receiving trabectedin treatment at the final data cutoff. The median PFS was 12.5 months (95 % CI: 7.4-not reached) in the trabectedin group, while 1.0 months (95 % CI: 0.3-1.0 months) in MCS subjects of the BSC group. The six-month progression-free rate was 100 % in the trabectedin group. One subject with MCS showed partial response, and the others in the trabectedin group showed stable disease. Overall survival of EMCS and MCS subjects was 26.4 months (range, 10. 4-26.4 months) in the trabectedin group. At the final data cutoff, two of five subjects were still alive.
Conclusions: This sub-analysis shows that trabectedin is effective for patients with EMCS and MCS compared with BSC. The efficacy results were better than previously reported data of TRS. These facts suggest that trabectedin become an important choice of treatment for patients with advanced EMCS or MCS who failed or were intolerable to standard chemotherapy.

DOI： 10.1186/s12885-016-2511-y

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Identification of circulating tumor derived microRNA signatures in osteosarcoma

Tomohiro Fujiwara, Koji Uotani, Aki Yoshida, Takuya Morita, Tadashi Komatsubara, Kazuhisa Sugiu, Toshinori Oman, Ken Takeda, Toshiyuki Kunisada, Yutaka Nezu, Akira Kawai, Hirotaka Kanzaki, Takahiro Ochiya, Toshifumi Ozaki

CANCER RESEARCH 76 2016年7月

Circulating cell-free microRNA as a novel biomarker for synovial sarcoma patients

Koji Uotani, Tomohiro Fujiwara, Aki Yoshida, Takuya Morita, Yutaka Nezu, Tadashi Komatsubara, Kazuhisa Sugiu, Takenori Uehara, Toshinori Omani, Ken Takeda, Toshiyuki Kunisada, Junya Toguchida, Akira Kawai, Takahiro Ochiya, Toshifumi Ozaki

CANCER RESEARCH 76 2016年7月

Tumor suppressor p53 reactivation by oncolytic adenovirus reverses chemoresistance in human osteosarcomas

Kazuhisa Sugiu, Hiroshi Tazawa, Joe Hasei, Shuhei Osaki, Yasuaki Yamakawa, Toshinori Omori, Tadashi Komatsubara, Kouji Uotani, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara

CANCER RESEARCH 76 2016年7月

Identification of exosomal surface marker derived from Ewing sarcoma cells

Aki Yoshida, Tomohiro Fujiwara, Koji Uotani, Yusuke Yoshioka, Koji Ueda, Takuya Morita, Ken Takeda, Toshiyuki Kunisada, Yutaka Nezu, Hiroyuki Kawashima, Takahiro Ochiya, Toshifumi Ozaki

CANCER RESEARCH 76 2016年7月

骨軟部肉腫切除における感染リスクファクター

望月雄介, 小松原将, 長谷井嬢, 国定俊之, 藤原智洋, 魚谷弘二, 杉生和久, 尾崎敏文

日本骨・関節感染症学会プログラム・抄録集 39回 90 - 90 2016年7月

Ablation of MCL1 expression by virally induced microRNA-29 reverses chemoresistance in human osteosarcomas 査読

Shuhei Osaki, Hiroshi Tazawa, Joe Hasei, Yasuaki Yamakawa, Toshinori Omori, Kazuhisa Sugiu, Tadashi Komatsubara, Tomohiro Fujiwara, Tsuyoshi Sasaki, Toshiyuki Kunisada, Aki Yoshida, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

SCIENTIFIC REPORTS 6 28953 2016年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NATURE PUBLISHING GROUP

Osteosarcoma is a rare disease diagnosed as malignant bone tumor. It is generally refractory to chemotherapy, which contributes to its poor prognosis. The reversal of chemoresistance is a major clinical challenge to improve the prognostic outcome of osteosarcoma patients. We developed a tumor-specific replication-competent oncolytic adenovirus, OBP-301 (telomelysin) and assessed its synergistic effects with chemotherapeutic agents (cisplatin and doxorubicin) using human osteosarcoma cell lines and a xenograft tumor model. The molecular mechanism underlying the chemosensitizing effect of OBP-301 was evaluated in aspects of apoptosis induction. OBP-301 inhibits anti-apoptotic myeloid cell leukemia 1 (MCL1) expression, which in turn leads to chemosensitization in human osteosarcoma cells. The siRNA-mediated knockdown of MCL1 expression sensitized human osteosarcoma cells to common chemotherapeutic agents. We also found that upregulation of microRNA-29 targeting MCL1 via virally induced transcriptional factor E2F-1 activation was critical for the enhancement of chemotherapy-induced apoptosis in osteosarcoma cells. Telomerase-specific oncolytic adenovirus synergistically suppressed the viability of human osteosarcoma cells in combination with chemotherapeutic agents. The combination treatment also significantly inhibited tumor growth, as compared to monotherapy, in an osteosarcoma xenograft tumor model. Our data suggest that replicative virus-mediated tumor-specific MCL1 ablation may be a promising strategy to attenuate chemoresistance in osteosarcoma patients.

DOI： 10.1038/srep28953

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創外固定を利用した悪性骨盤腫瘍に対する早期リハビリテーション

国定俊之, 藤原智洋, 野田知之, 堅山佳美, 千田益生, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine ( JARM2016 ) I438 - I438 2016年6月

脊椎に発生したpigmented villonodular synovitisの2例

魚谷弘二, 藤原智洋, 瀧川朋亨, 荒瀧慎也, 杉本佳久, 武田健, 国定俊之, 田中雅人, 尾崎敏文

日本整形外科学会雑誌 90 ( 6 ) S1353 - S1353 2016年6月

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