TY - JOUR A1 - Eckardt, Jan-Niklas A1 - Stasik, Sebastian A1 - Kramer, Michael A1 - Röllig, Christoph A1 - Krämer, Alwin A1 - Scholl, Sebastian A1 - Hochhaus, Andreas A1 - Crysandt, Martina A1 - Brümmendorf, Tim H. A1 - Naumann, Ralph A1 - Steffen, Björn A1 - Kunzmann, Volker A1 - Einsele, Hermann A1 - Schaich, Markus A1 - Burchert, Andreas A1 - Neubauer, Andreas A1 - Schäfer-Eckart, Kerstin A1 - Schliemann, Christoph A1 - Krause, Stefan W. A1 - Herbst, Regina A1 - Hänel, Mathias A1 - Frickhofen, Norbert A1 - Noppeney, Richard A1 - Kaiser, Ulrich A1 - Baldus, Claudia D. A1 - Kaufmann, Martin A1 - Rácil, Zdenek A1 - Platzbecker, Uwe A1 - Berdel, Wolfgang E. A1 - Mayer, Jiří A1 - Serve, Hubert A1 - Müller-Tidow, Carsten A1 - Ehninger, Gerhard A1 - Stölzel, Friedrich A1 - Kroschinsky, Frank A1 - Schetelig, Johannes A1 - Bornhäuser, Martin A1 - Thiede, Christian A1 - Middeke, Jan Moritz T1 - Loss-of-function mutations of BCOR are an independent marker of adverse outcomes in intensively treated patients with acute myeloid leukemia JF - Cancers N2 - Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The BCL6 corepressor (BCOR) and its homolog, the BCL6 corepressor-like 1 (BCORL1), have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. BCOR and BCORL1 mutations were found in 71 (4.6%) and 53 patients (3.5%), respectively. Frequently co-mutated genes were DNTM3A, TET2 and RUNX1. Mutated BCORL1 and loss-of-function mutations of BCOR were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of BCOR had a significantly reduced median event-free survival (HR = 1.464 (95%-Confidence Interval (CI): 1.005–2.134), p = 0.047), relapse-free survival (HR = 1.904 (95%-CI: 1.163–3.117), p = 0.01), and trend for reduced overall survival (HR = 1.495 (95%-CI: 0.990–2.258), p = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of BCOR regarding risk stratification in AML, which may influence treatment allocation. KW - acute myeloid leukemia KW - BCOR KW - BCORL1 KW - loss-of-function KW - risk stratification KW - survival Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236735 SN - 2072-6694 VL - 13 IS - 9 ER - TY - JOUR A1 - Kaiser, Mathias A1 - Burek, Malgorzata A1 - Britz, Stefan A1 - Lankamp, Frauke A1 - Ketelhut, Steffi A1 - Kemper, Björn A1 - Förster, Carola A1 - Gorzelanny, Christian A1 - Goycoolea, Francisco M. T1 - The influence of capsaicin on the integrity of microvascular endothelial cell monolayers JF - International Journal of Molecular Sciences N2 - Microvascular endothelial cells are an essential part of many biological barriers, such as the blood–brain barrier (BBB) and the endothelium of the arteries and veins. A reversible opening strategy to increase the permeability of drugs across the BBB could lead to improved therapies due to enhanced drug bioavailability. Vanilloids, such as capsaicin, are known to reversibly open tight junctions of epithelial and endothelial cells. In this study, we used several in vitro assays with the murine endothelial capillary brain cells (line cEND) as a BBB model to characterize the interaction between capsaicin and endothelial tight junctions. KW - tight junctions KW - capsaicin KW - endothelial cells Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284865 SN - 1422-0067 VL - 20 IS - 1 ER -