title: Trabectedin is a promising antitumour agent for synovial sarcoma.
abstract: 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(®)), 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.
authors.affiliation: a Department of Orthopaedic Surgery , Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, Osaka 565 0871 , Japan.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Yasui
authors.affiliation: a Department of Orthopaedic Surgery , Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, Osaka 565 0871 , Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Imura
authors.affiliation: a Department of Orthopaedic Surgery , Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, Osaka 565 0871 , Japan.
authors.forename: Hidetatsu
authors.initials: H
authors.lastname: Outani
authors.affiliation: a Department of Orthopaedic Surgery , Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, Osaka 565 0871 , Japan.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Hamada
authors.affiliation: a Department of Orthopaedic Surgery , Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, Osaka 565 0871 , Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Nakai
authors.affiliation: a Department of Orthopaedic Surgery , Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, Osaka 565 0871 , Japan.
authors.forename: Shutaro
authors.initials: S
authors.lastname: Yamada
authors.affiliation: a Department of Orthopaedic Surgery , Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, Osaka 565 0871 , Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takenaka
authors.affiliation: b Department of Biology , Osaka Medical Center for Cancer and Cardiovascular Diseases , 1-3-2 Nakamichi, Higashinari-ku, Osaka 537 8511 , Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Sasagawa
authors.affiliation: c Musculoskeletal Oncology Service , Osaka Medical Center for Cancer and Cardiovascular Diseases , 1-3-2 Nakamichi, Higashinari-ku, Osaka 537 8511 , Japan.
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Araki
authors.affiliation: b Department of Biology , Osaka Medical Center for Cancer and Cardiovascular Diseases , 1-3-2 Nakamichi, Higashinari-ku, Osaka 537 8511 , Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Itoh
authors.affiliation: a Department of Orthopaedic Surgery , Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, Osaka 565 0871 , Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Myoui
authors.affiliation: a Department of Orthopaedic Surgery , Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, Osaka 565 0871 , Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
authors.affiliation: a Department of Orthopaedic Surgery , Osaka University Graduate School of Medicine , 2-2 Yamadaoka, Suita, Osaka 565 0871 , Japan.|b Department of Biology , Osaka Medical Center for Cancer and Cardiovascular Diseases , 1-3-2 Nakamichi, Higashinari-ku, Osaka 537 8511 , Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Naka
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019313:BRCA1 Protein / Q000032:analysis / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis; D004149:Dioxoles / Q000494:pharmacology*; D004720:Endonucleases / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis / Q000096:biosynthesis; D013584:Sarcoma, Synovial / Q000473:pathology*; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D000077606:Trabectedin; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D004149:Dioxoles; D004720:Endonucleases; D009687:Nuclear Proteins; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5; C492913:BRCA1 protein, human; C071447:ERCC1 protein, human
keywords: BRCA1; ERCC1; ERCC5; Synovial sarcoma; Trabectedin