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• W2563194003 abstract "// Levent Dizdar 1 , Kira A. Oesterwind 1 , Jasmin C. Riemer 2 , Thomas A. Werner 1 , Sabrina Mersch 1 , Birte Möhlendick 1 , Sina C. Schütte 1 , Pablo E. Verde 3 , Katharina Raba 4 , Stefan A. Topp 1 , Nikolas H. Stoecklein 1 , Irene Esposito 2 , Wolfram T. Knoefel 1 , Andreas Krieg 1 1 Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany 2 Institute of Pathology, Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany 3 Coordination Centre for Clinical Trials, Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany 4 Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany Correspondence to: Andreas Krieg, email: andreas.krieg@med.uni-duesseldorf.de Keywords: survivin, XIAP, GEP-NEN, neuroendocrine neoplasia, inhibitor of apoptosis protein Received: September 18, 2016     Accepted: November 22, 2016     Published: December 26, 2016 ABSTRACT Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) represent a rare and heterogenous tumor entity. Importantly, the highly proliferative subgroup of neuroendocrine carcinoma (GEP-NEC) is characterized by high resistance to conventional chemotherapy. Consequently, there is an urgent need to identify novel therapeutic targets, especially for GEP-NEC. Thus, we focused on Inhibitor of apoptosis protein (IAP) family members survivin and XIAP that orchestrate inhibition of apoptosis, induce resistance against chemotherapeutics and facilitate tumor metastasis. Copy number gains (CNGs) could be detected by microarray comparative genomic hybridization for survivin and XIAP in 60 % and 26.7 % of all GEP-NENs, respectively. Immunohistochemical staining of tissue specimens from 77 consecutive patients with GEP-NEN demonstrated increased survivin protein expression levels in tissue specimens of highly proliferative GEP-NEC or GEP-NEN located in the stomach and colon. In contrast, XIAP overexpression was associated with advanced tumor stages. Knockdown of survivin and XIAP markedly reduced cell proliferation and tumor growth. In vitro, YM155 induced apoptotic cell death accompanied by a reduction in cell proliferation and inhibited GEP-NEC xenograft growth. Taken together, our data provide evidence for a biological relevance of these IAPs in GEP-NEN and support a potential role of survivin as therapeutic target especially in the subgroup of aggressive GEP-NEC." @default.
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• W2563194003 date "2016-12-26" @default.
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• W2563194003 title "Preclinical assesement of survivin and XIAP as prognostic biomarkers and therapeutic targets in gastroenteropancreatic neuroendocrine neoplasia" @default.
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• W2563194003 doi "https://doi.org/10.18632/oncotarget.14207" @default.
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