201 research outputs found

    New methods at the transition from research to routine diagnostics

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    Hintergrund:Die Pathologie, traditionell auf Klassifikation und Diagnose fokussiert, entwickelt sich durch neue Technologien kontinuierlich weiter. Fortschritte in Proteomik, Epigenetik, Multiplex-Gewebefärbung und 3D-Bildgebung erweitern die Möglichkeiten der klassischen Morphologie.Ziel der Studie:Ziel dieser Studie ist es, zu untersuchen, wie moderne Technologien die diagnostische Genauigkeit und die resultierende Therapieauswahl verbessern können und wie sie in die pathologische Routinediagnostik integriert werden können.Materia und Methoden:Es wurden aktuelle Studien zu Proteomik, Epigenetik, Multiplex-Gewebefärbung und 3D-Gewebe-Bildgebung analysiert, um deren Anwendung und Herausforderungen in der klinischen Implementierung zu bewerten.Ergebnisse:Die Analyse zeigt erhebliches Potenzial für die pathologische Diagnostik. Proteomik ermöglicht ein tieferes Verständnis der molekularen Tumorarchitektur, während Epigenetik und 3D-Genomarchitektur neue Einblicke in genetische Regulation und Tumorheterogenität geben. Multiplex-Gewebefärbung und 3D-Gewebe-Bildgebung verbessern die räumliche Gewebeanalyse.Diskussion:Trotz des Potenzials zur Verbesserung der Diagnostik behindern hohe Kosten, technische Komplexität und fehlende Standardisierung die Integration in die klinische Praxis. Dennoch bieten diese Technologien vielversprechende Ansätze zur Optimierung der Diagnostik und Therapieauswahl. Forschung und interdisziplinäre Zusammenarbeit sind entscheidend, um diese Innovationen in die klinische Routine zu integrieren.Background:Pathology, traditionally focused on classification and diagnosis, is continuously evolving through new technologies. Advances in proteomics, epigenetics, tissue staining, and 3D imaging expand the possibilities of classical morphology.Aim of the study:The aim of this study was to investigate how modern technologies can improve diagnostic accuracy and therapy selection and how they can be integrated into pathologic routine diagnostics.Materials and methods:Recent studies in proteomics, epigenetics, multiplex tissue staining, and 3D tissue imaging were analyzed to assess their application and the challenges of clinical implementation.Results:The analysis shows significant potential for pathologic diagnostics. Proteomics provides a deeper understanding of the molecular architecture of tumors, while epigenetics and 3D genome architecture offer new insights into genetic regulation and tumor heterogeneity. Multiplex tissue staining and 3D tissue imaging improve spatial tissue analysis.Discussion:Despite the potential to improve diagnostics, high costs, technical complexity, and lack of standardization hinder integration into clinical practice. Nevertheless, these technologies offer promising approaches for optimizing diagnostics and therapy selection. Research and interdisciplinary collaboration are crucial to successfully integrating these innovations into routine clinical practice

    Recent advances and conceptual changes in the classification of neuroendocrine tumors of the thymus

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    Abstract Neuroendocrine tumors of the thymus (TNET) are exceedingly rare neoplasms. Their histomorphology is identical to neuroendocrine tumors elsewhere in the body (in particular the lungs) and bears no similarity with thymomas and thymic carcinomas. Recent molecular findings have profoundly changed our perception of these tumors and may impact future histological classification systems.Projekt DEA

    The prognostic capacities of CBP and p300 in locally advanced rectal cancer

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    CREB-binding protein (CBP) and p300 represent histone acetyltransferases (HATs) and transcriptional coactivators that play essential roles in tumour initiation and progression. Both proteins are generally thought to function as tumour suppressors, although their distinct roles in colorectal cancer (CRC) remain inconsistent and ambiguous. Thus, we analysed the expression of these two HATs in human tissue samples from patients with locally advanced rectal cancer via immunohistochemistry and evaluated their potential impacts on future CRC diagnosis and treatment

    Ketoprofen allergic reactions

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    Topical ketoprofen (KP) is widely used because of its anti-inflammatory effect. Parallel with its popular usage, the number of reported cases of ketoprofen-induced photoallergic contact dermatitis has increased. A review of the literature was made to evaluate the spectrum of cross sensitization in patients with ketoprofen-induced photoallergic contact dermatitis using ketoprofen and other structurally similar chemicals and sunscreens, fragrance components, as well as the presence of prolonged photosensitivity related to it. Furthermore, the distinction between true cross-reactivity and concomitant sensitization may be difficult. Therefore, further investigations are needed to gain a more complete understanding of this important topic. This article also reviews some patents related to alternative treatment of musculoskeletal diseases and/or treatment of allergic reactions due to NSAIDs use

    Abstract 1500: The role of FUBP1 in the hematopoietic system and leukemia

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    Abstract The transcriptional regulator FUBP1 (Far Upstream Element Binding Protein 1) acts as an oncoprotein in hepatocellular carcinoma (HCC) and is important for hematopoietic stem cell (HSC) self-renewal and erythroid maturation in mice. In this study, we investigated the transcriptional network by which FUBP1 controls hematopoiesis and elucidated the relevance of FUBP1 for human erythropoiesis. Furthermore, we shed light on the role of FUBP1 in leukemia initiating cells. Searching for upstream-regulators of FUBP1, we identified E-boxes as potential TAL1 binding sites in the FUBP1 promoter. Indeed, we demonstrated the regulation of FUBP1 expression by TAL1 in human primary CD34+ donor cells. In chromatin immunoprecipitation (ChIP) experiments, the binding of TAL1 to the FUBP1 promoter increased during erythroid differentiation, correlating with up-regulated FUBP1 and TAL1 expression. Activation of the FUBP1 promoter by TAL1 binding was confirmed in luciferase assays. We observed a reduction in erythroid colony-forming units and glycophorin A positive cells derived from erythroid differentiated human CD34+ cells upon knockdown of FUBP1, supporting the hypothesis that FUBP1 is required for efficient erythropoiesis. In the transduction/transplantation leukemia mouse models for BCR-ABL1+ CML and MLL-AF9+ AML, we observed that Fubp1 knockdown resulted in reduced total cell and progenitor cell numbers. In CML, Fubp1 knockdown cells showed lower cell cycle activity and increased apoptosis. Consistently, CML and AML mice transplanted with Fubp1 knockdown cells survived longer than control mice that received transduced bone marrow expressing wildtype FUBP1 levels. Furthermore, pharmacological treatment of AML mice with the FUBP1 inhibitor irinotecan prolonged their survival significantly as a single drug or in combination with Ara-C. Analysis of FUBP1 expression in bone sections derived from CML and AML patients, and from healthy donors by immunohistochemistry showed no increased FUBP1 expression in leukemic samples, but we noticed a shorter overall survival in those AML patients with strong FUBP1 expression. In CML patients, FUBP1 levels correlate with the disease stage. Thus, elevated expression of FUBP1 might be an indicator for the aggressiveness of leukemia. Our data identify TAL1 as an FUBP1 upstream-regulator and confirm the importance of FUBP1 for HSC self-renewal and erythroid maturation, not only in murine but also in human cells. Furthermore, FUBP1 acts as an oncogenic factor in leukemia. Our findings might provide important evidence for the potential use of FUBP1 in clinical settings, e.g. as a molecular target for the treatment of leukemia patients and as a modulator for the production of red cells. Citation Format: Marlene Steiner, Van T. Hoang, Jasmin Yillah, Katharina Gerlach, Jörn Lausen, Hans-Michael Kvasnicka, Thomas Oellerich, Hanibal Bohnenberger, Daniela Krause, Martin Zörnig. The role of FUBP1 in the hematopoietic system and leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1500
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