Full metadata record
DC Field | Value | Language |
---|---|---|
dc.creator | Hoffmeister-Wittmann, P. (Paula) | - |
dc.creator | Mock, A. (Andreas) | - |
dc.creator | Nichetti, F. (Federico) | - |
dc.creator | Korell, F. (Felix) | - |
dc.creator | Heilig, C.E. (Christoph E.) | - |
dc.creator | Scherr, A.L. (Anna Lena) | - |
dc.creator | Günther, M. (Michael) | - |
dc.creator | Albrecht, T. (Thomas) | - |
dc.creator | Kelmendi, E. (Eblina) | - |
dc.creator | Xu, K. (Kaiyu) | - |
dc.creator | Nader, L. (Luisa) | - |
dc.creator | Kessler, A. (Annika) | - |
dc.creator | Schmitt, N. (Nathalie) | - |
dc.creator | Fritzsche, S. (Sarah) | - |
dc.creator | Weiler, S. (Sofia) | - |
dc.creator | Sobol, B. (Benjamin) | - |
dc.creator | Stenzinger, A. (Albrecht) | - |
dc.creator | Boeck, S. (Stefan) | - |
dc.creator | Westphalen, C.B. (Christoph B.) | - |
dc.creator | Schulze-Osthoff, K. (Klaus) | - |
dc.creator | Trojan, J. (Jörg) | - |
dc.creator | Kindler, T. (Thomas) | - |
dc.creator | Weichert, W. (Wilko) | - |
dc.creator | Spiekermann, K. (Karsten) | - |
dc.creator | Bitzer, M. (Michael) | - |
dc.creator | Folprecht, G. (Gunnar) | - |
dc.creator | Illert, A.L. (Anna L.) | - |
dc.creator | Boerries, M. (Melanie) | - |
dc.creator | Klauschen, F. (Frederick) | - |
dc.creator | Ochsenreiter, S. (Sebastian) | - |
dc.creator | Siveke, J. (Jens) | - |
dc.creator | Bauer, S. (Sebastian) | - |
dc.creator | Glimm, H. (Hanno) | - |
dc.creator | Brors, B. (Benedikt) | - |
dc.creator | Hüllein, J. (Jennifer) | - |
dc.creator | Hübschmann, D. (Daniel) | - |
dc.creator | Uhrig, S. (Sebastian) | - |
dc.creator | Horak, P. (Peter) | - |
dc.creator | Kreutzfeld, S. (Simon) | - |
dc.creator | Banales, J.M. (Jesús M.) | - |
dc.creator | Springfeld, C. (Christoph) | - |
dc.creator | Jäger, D. (Dirk) | - |
dc.creator | Schirmacher, P. (Peter) | - |
dc.creator | Roessler, S. (Stephanie) | - |
dc.creator | Ormanns, S. (Steffen) | - |
dc.creator | Goeppert, B. (Benjamin) | - |
dc.creator | Fröhling, S. (Stefan) | - |
dc.creator | Köhler, B.C. (Bruno C.) | - |
dc.date.accessioned | 2023-01-20T09:16:20Z | - |
dc.date.available | 2023-01-20T09:16:20Z | - |
dc.date.issued | 2022 | - |
dc.identifier.citation | Hoffmeister-Wittmann, P.; Mock, A.; Nichetti, F.; et al. "Bcl-x(L) as prognostic marker and potential therapeutic target in cholangiocarcinoma". Liver International. 42 (12), 2022, 2855 - 2870 | es |
dc.identifier.issn | 1478-3223 | - |
dc.identifier.uri | https://hdl.handle.net/10171/65016 | - |
dc.description.abstract | Intrahepatic, perihilar, and distal cholangiocarcinoma (iCCA, pCCA, dCCA) are highly malignant tumours with increasing mortality rates due to therapy resistances. Among the mechanisms mediating resistance, overexpression of anti-apoptotic Bcl-2 proteins (Bcl-2, Bcl-x(L), Mcl-1) is particularly important. In this study, we investigated whether antiapoptotic protein patterns are prognostically relevant and potential therapeutic targets in CCA. Bcl-2 proteins were analysed in a pan-cancer cohort from the NCT/DKFZ/DKTK MASTER registry trial (n = 1140, CCA n = 72) via RNA-sequencing and transcriptome-based protein activity interference revealing high ranks of CCA for Bcl-x(L) and Mcl-1. Expression of Bcl-x(L), Mcl-1, and Bcl-2 was assessed in human CCA tissue and cell lines compared with cholangiocytes by immunohistochemistry, immunoblotting, and quantitative-RT-PCR. Immunohistochemistry confirmed the upregulation of Bcl-x(L) and Mcl-1 in iCCA tissues. Cell death of CCA cell lines upon treatemnt with specific small molecule inhibitors of Bcl-x(L) (Wehi-539), of Mcl-1 (S63845), and Bcl-2 (ABT-199), either alone, in combination with each other or together with chemotherapeutics was assessed by flow cytometry. Targeting Bcl-x(L) induced cell death and augmented the effect of chemotherapy in CCA cells. Combined inhibition of Bcl-x(L) and Mcl-1 led to a synergistic increase in cell death in CCA cell lines. Correlation between Bcl-2 protein expression and survival was analysed within three independent patient cohorts from cancer centers in Germany comprising 656 CCA cases indicating a prognostic value of Bcl-x(L) in CCA depending on the CCA subtype. Collectively, these observations identify Bcl-x(L) as a key protein in cell death resistance of CCA and may pave the way for clinical application. | - |
dc.description.sponsorship | DKTK Joint Funding Program; NCT Molecular Precision Oncology Program; “Fundación Científica de la Asociación Española Contra el Cáncer”; Department of Health of the Basque Country, Grant/ Award Number: 2017111010; CIBERehd (ISCIII); Miguel Servet Program, Grant/ Award Number: CPII19/00008; Spanish Carlos III Health Institute (ISCIII), Grant/Award Number: PI21/00922 and PI18/01075; Abbvie; PSC Partners Seeking A Cure Foundation; Deutsche Krebshilfe, Grant/Award Number: 70113593 and 70113922; Deutsche Forschungsgemeinschaft, Grant/Award Number: KO-5205/3–1, KO-5205/1–1 and 314905040 – SFB/TRR 209 | - |
dc.language.iso | en | - |
dc.rights | info:eu-repo/semantics/openAccess | - |
dc.subject | Apoptosis | - |
dc.subject | Bcl-2 | - |
dc.subject | Bcl-x(L) | - |
dc.subject | Chemotherapy | - |
dc.subject | Cholangiocarcinoma | - |
dc.subject | Mcl-1 | - |
dc.title | Bcl-x(L) as prognostic marker and potential therapeutic target in cholangiocarcinoma | - |
dc.type | info:eu-repo/semantics/article | - |
dc.description.note | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, | - |
dc.identifier.doi | 10.1111/liv.15392 | - |
dadun.citation.endingPage | 2870 | - |
dadun.citation.number | 12 | - |
dadun.citation.publicationName | Liver International | - |
dadun.citation.startingPage | 2855 | - |
dadun.citation.volume | 42 | - |
Files in This Item:
Statistics and impact
Items in Dadun are protected by copyright, with all rights reserved, unless otherwise indicated.