title: Examination of survivin expression in 50 chordoma specimens--A histological and in vitro study.
abstract: Chordomas mainly arise along the axial skeleton and are characterized by their slow but destructive growth. Prognosis and quality of life are poor because treatment options are mainly limited to surgery and radiotherapy. Survivin, a member of the apoptosis inhibitor protein family, functions as a key regulator of mitosis and programmed cell death, and is overexpressed in many tumor types. The aim of this study was to determine the role of survivin in chordomas. Survivin expression was investigated in 50 chordoma samples and three chordoma cell lines using immunohistochemistry. The intensity of immunostaining was evaluated in regard to the development of recurrences. The immunohistochemical results were correlated with clinical parameters like gender, age, tumor size, and location and were performed in primary chordomas as well as in recurrent lesions. Furthermore, survivin knockdown experiments on chordoma cell lines were performed. YM155 decreased the growth behavior of chordoma cells dose- and time dependently. Transient knockdown of survivin led to a G2/M arrest, decreased proliferation, consistently induced an increase of polyploidy and morphological changes, and induced apoptosis. The resultant data from this study suggest that survivin plays a cell cycle-progressive role in chordomas. Hence, regulation of survivin by YM155 is a promising new target for the development of new therapeutic drugs.
authors: Department of Orthopedic Surgery, Medical University of Graz, Graz, Austria.
authors: Elke V
authors: EV
authors: Froehlich
authors: Beate
authors: B
authors: Rinner
authors: Alexander J A
authors: AJ
authors: Deutsch
authors: Katharina
authors: K
authors: Meditz
authors: Heike
authors: H
authors: Knausz
authors: Katharina
authors: K
authors: Troppan
authors: Susanne
authors: S
authors: Scheipl
authors: Christine
authors: C
authors: Wibmer
authors: Andreas
authors: A
authors: Leithner
authors: Bernadette
authors: B
authors: Liegl
authors: Birgit
authors: B
authors: Lohberger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002817:Chordoma / Q000188:drug therapy / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009285:Naphthoquinones / Q000494:pharmacology / Q000627:therapeutic use; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D034741:RNA, Small Interfering; D012189:Retrospective Studies; D012888:Skull Neoplasms / Q000378:metabolism*; D013125:Spinal Neoplasms / Q000378:metabolism*; D000077022:Survivin; D055815:Young Adult
chemical_list: C107489:BIRC5 protein, human; D007093:Imidazoles; D051034:Inhibitor of Apoptosis Proteins; D009285:Naphthoquinones; D034741:RNA, Small Interfering; D000077022:Survivin; C523798:sepantronium
keywords: YM155; cell cycle; chordoma; survivin