Trabectedin is a promising antitumour agent for synovial sarcoma

被引:7
作者
Yasui, Hirohiko [1 ]
Imura, Yoshinori [1 ]
Outani, Hidetatsu [1 ]
Hamada, Ken-ichiro [1 ]
Nakai, Takaaki [1 ]
Yamada, Shutaro [1 ]
Takenaka, Satoshi [1 ]
Sasagawa, Satoru [2 ]
Araki, Nobuhito [3 ]
Itoh, Kazuyuki [2 ]
Myoui, Akira [1 ]
Yoshikawa, Hideki [1 ]
Naka, Norifumi [1 ,2 ]
机构
[1] Osaka Univ, Grad Sch Med, Dept Orthopaed Surg, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan
[2] Osaka Med Ctr Canc & Cardiovasc Dis, Dept Biol, Higashinari Ku, 1-3-2 Nakamichi, Osaka 5378511, Japan
[3] Osaka Med Ctr Canc & Cardiovasc Dis, Musculoskeletal Oncol Serv, Higashinari Ku, 1-3-2 Nakamichi, Osaka 5378511, Japan
基金
日本学术振兴会;
关键词
Synovial sarcoma; Trabectedin; ERCC1; ERCC5; BRCA1; SOFT-TISSUE SARCOMA; DNA-REPAIR PATHWAYS; EWING SARCOMA; PHASE-II; ECTEINASCIDIN-743; ET-743; RETROSPECTIVE ANALYSIS; NUCLEOTIDE-EXCISION; OVARIAN; CANCER; CELLS;
D O I
10.1080/1120009X.2015.1133013
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Synovial sarcoma (SS) is an aggressive soft tissue tumour with poor prognosis. Using five human SS cell lines, we examined the cytotoxic effects of trabectedin (ET-743; Yondelis (R)), a novel marine natural product, which was approved in Europe for the treatment of soft tissue sarcomas (STS). The significant growth inhibitory effects were observed in all SS cell lines below nanomolar concentration of trabectedin. Furthermore, trabectedin significantly suppressed the tumour growth in xenograft models. Flow cytometer analysis in vitro and immunohistochemical analysis in vivo revealed its effect of cell cycle inhibition and apoptosis induction. We also examined the expression of ERCC1, 5 and BRCA1 in SS cell lines and clinical samples, and majority of them showed highly trabectedin-sensitive pattern as previously reported in other cancers. Our preclinical data indicated that trabectedin could be a promising therapeutic option for patients with SS.
引用
收藏
页码:417 / 424
页数:8
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