| |  Online-Ressource |
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| Verfasst von: | Finke, Daniel [VerfasserIn]  |
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| | Heckmann, Markus B. [VerfasserIn] |
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| | Salatzki, Janek [VerfasserIn] |
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| | Riffel, Johannes [VerfasserIn] |
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| | Herpel, Esther [VerfasserIn] |
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| | Heinzerling, Lucie M. [VerfasserIn] |
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| | Meder, Benjamin [VerfasserIn] |
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| | Völkers, Mirko [VerfasserIn] |
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| | Müller, Oliver J. [VerfasserIn] |
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| | Frey, Norbert [VerfasserIn] |
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| | Katus, Hugo [VerfasserIn] |
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| | Leuschner, Florian [VerfasserIn] |
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| | Kaya, Ziya [VerfasserIn] |
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| | Lehmann, Lorenz [VerfasserIn] |
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| Titel: | Comparative transcriptomics of immune checkpoint inhibitor myocarditis identifies guanylate binding protein 5 and 6 dysregulation |
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| Verf.angabe: | Daniel Finke, Markus B. Heckmann, Janek Salatzki, Johannes Riffel, Esther Herpel, Lucie M. Heinzerling, Benjamin Meder, Mirko Völkers, Oliver J. Müller, Norbert Frey, Hugo A. Katus, Florian Leuschner, Ziya Kaya and Lorenz H. Lehmann |
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| E-Jahr: | 2021 |
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| Jahr: | 20 May 2021 |
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| Umfang: | 15 S. |
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| Fussnoten: | Gesehen am 25.02.2022 |
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| Titel Quelle: | Enthalten in: Cancers |
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| Ort Quelle: | Basel : MDPI, 2009 |
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| Jahr Quelle: | 2021 |
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| Band/Heft Quelle: | 13(2021), 10, Artikel-ID 2498, Seite 1-15 |
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| ISSN Quelle: | 2072-6694 |
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| Abstract: | Immune checkpoint inhibitors (ICIs) are revolutionizing cancer treatment. Nevertheless, their increasing use leads to an increase of immune-related adverse events (irAEs). Among them, ICI-associated myocarditis (ICIM) is a rare irAE with a high mortality rate. We aimed to characterize the transcriptional changes of ICIM myocardial biopsies and their possible implications. Patients suspected for ICIM were assessed in the cardio-oncology units of University Hospitals Heidelberg and Kiel. Via RNA sequencing of myocardial biopsies, we compared transcriptional changes of ICIM (n = 9) with samples from dilated cardiomyopathy (DCM, n = 11), virus-induced myocarditis (VIM, n = 5), and with samples of patients receiving ICIs without any evidence of myocarditis (n = 4). Patients with ICIM (n = 19) showed an inconsistent clinical presentation, e.g., asymptomatic elevation of cardiac biomarkers (hs-cTnT, NT-proBNP, CK), a drop in left ventricular ejection fraction, or late gadolinium enhancement in cMRI. We found 3784 upregulated genes in ICIM (FDR < 0.05). In the overrepresented pathway ‘response to interferon-gamma’, we found guanylate binding protein 5 and 6 (compared with VIM: GBP5 (log2 fc 3.21), GBP6 (log2 fc 5.37)) to be significantly increased in ICIM on RNA- and protein-level. We conclude that interferon-gamma and inflammasome-regulating proteins, such as GBP5, may be of unrecognized significance in the pathophysiology of ICIM. |
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| DOI: | doi:10.3390/cancers13102498 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.3390/cancers13102498 |
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| | Volltext: https://www.mdpi.com/2072-6694/13/10/2498 |
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| | DOI: https://doi.org/10.3390/cancers13102498 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | CD8 |
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| | comparative transcriptomics |
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| | CTLA4 |
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| | ICI-associated myocarditis |
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| | ICIM |
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| | PD1 |
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| | PDL-1 |
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| | virus myocarditis |
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| K10plus-PPN: | 179389244X |
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| Verknüpfungen: | → Zeitschrift |
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Comparative transcriptomics of immune checkpoint inhibitor myocarditis identifies guanylate binding protein 5 and 6 dysregulation / Finke, Daniel [VerfasserIn]; 20 May 2021 (Online-Ressource)
