A5016044284- Cell death mechanisms and regulation
- Cancer, Hypoxia, and Metabolism
- Effects of Radiation Exposure
- Synthesis and Characterization of Heterocyclic Compounds
- Glioma Diagnosis and Treatment
- Quinazolinone synthesis and applications
- Phenothiazines and Benzothiazines Synthesis and Activities
- Cancer-related Molecular Pathways
- PI3K/AKT/mTOR signaling in cancer
- Adenosine and Purinergic Signaling
- Mitochondrial Function and Pathology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Inflammatory mediators and NSAID effects
- Autophagy in Disease and Therapy
- DNA Repair Mechanisms
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Caveolin-1 and cellular processes
- Radiation Therapy and Dosimetry
- Cancer Mechanisms and Therapy
- Immune Response and Inflammation
- Cancer therapeutics and mechanisms
- Cancer Cells and Metastasis
- PARP inhibition in cancer therapy
University of Duisburg-Essen
2016-2025
Essen University Hospital
2015-2024
Institute of Cell Biology
2012-2017
Institute of Clinical Cancer Research
2016
Azienda Ospedaliera Citta' della Salute e della Scienza di Torino
2016
University of Turin
2016
Universidad de Málaga
2012
Helmholtz-Zentrum Dresden-Rossendorf
2012
University of Tübingen
2001-2010
Ludwig-Maximilians-Universität München
2010
Abstract Many receptor systems use clustering for transmembrane signaling. In this study, we show that acid sphingomyelinase (ASM) is essential the of CD40. Stimulation lymphocytes via CD40 ligation results in ASM translocation from intracellular stores, most likely vesicles, into distinct membrane domains on extracellular surface plasma membrane. Surface initiates a release extracellularly oriented ceramide, which turn mediates sphingolipid-rich domains. ASM, and colocalize cap-like...
Hypoxia occurs in many pathological conditions, including inflammation and cancer. Within this context, hypoxia was shown to inhibit but also promote T cell responses. Due controversial function, we aimed explore whether an insufficient anti-tumour response during colitis-associated colon cancer could be ascribed a hypoxic microenvironment.Colitis-associated induced wildtype mice, as well immunity were analysed the colonic tumour tissues. In addition, CD4+ effector cells regulatory cultured...
Targeting and stabilizing distinct kinase conformations is an instrumental strategy for dissecting conformation-dependent signaling of protein kinases. Herein the structure-based design, synthesis, evaluation pleckstrin homology (PH) domain-dependent covalent-allosteric inhibitors (CAIs) Akt reported. These bind covalently to a cysteine thereby stabilize inactive conformation. modulators exhibit high potency selectivity, represent innovative approach chemical biology medicinal chemistry research.
Osmotic erythrocyte shrinkage leads to activation of cation channels with subsequent Ca2+ entry and stimulates a sphingomyelinase formation ceramide. ceramide then activate scramblase leading breakdown phosphatidylserine asymmetry the cell membrane. The mediators accounting for exposure remained elusive. study demonstrates that platelet-activating factor (PAF) is released from erythrocytes upon hyperosmotic shrinkage. experiments further disclose presence PAF receptors in show sphingomyelin...
The cyclooxygenase (COX)-2 inhibitor Celecoxib may inhibit cancer cell growth independently of its capacity to block the COX-2 enzyme. inhibitory effect had been attributed pro-apoptotic effects. However, molecular details Celecoxib-induced apoptosis have not analyzed yet. To differentiate between death receptor and mitochondrial signaling pathways, induction upon treatment with was tested in Jurkat T- BJAB B-lymphoma lines defects either pathway. dose- time-dependent cells involving i)...
Radiation-induced normal tissue toxicity is closely linked to endothelial cell (EC) damage and dysfunction (acute effects). However, the underlying mechanisms of radiation-induced adverse late effects with respect vascular compartment remain elusive, no causative radioprotective treatment available date.The importance injury EC for in lungs after whole thorax irradiation (WTI) was investigated using a mouse model pneumopathy. We show that WTI induces loss as long-term complication, which...
Pronounced resistance of lung cancer cells to radiotherapy and chemotherapy is a major barrier successful treatment. Herein, both tumor hypoxia the upregulation cellular antioxidant defense systems observed during malignant progression can contribute radioresistance. We recently found that exposure chronic cycling severe hypoxia/reoxygenation stress results in glutamine-dependent glutathione (GSH) levels associated radiation opening novel routes for cell-specific radiosensitization. Here, we...
Abstract Radiation-induced pulmonary fibrosis is a severe side effect of thoracic irradiation, but its pathogenesis remains poorly understood and no effective treatment available. In this study, we investigated the role extracellular adenosine as generated by ecto-5′-nucleotidase CD73 in development after irradiation. Exposure wild-type C57BL/6 mice to single dose (15 Gray) whole thorax irradiation triggered progressive increase activity lung between 3 30 weeks postirradiation. parallel,...
Abstract Resistance against radio(chemo)therapy-induced cell death is a major determinant of oncological treatment failure and remains perpetual clinical challenge. The underlying mechanisms are manifold demand for comprehensive, cancer entity- subtype-specific examination. In the present study, resistance radiotherapy was systematically assessed in panel human head-and-neck squamous carcinoma (HNSCC) lines xenotransplants derived thereof with overarching aim to extract master regulators...
Abstract Metabolic rewiring is the result of increasing demands and proliferation cancer cells, leading to changes in biological activities responses treatment cells. The mitochondrial citrate transport protein SLC25A1 involved metabolic reprogramming offering a strategy induce bottlenecks relevant radiosensitization through accumulation oncometabolite D-2-hydroxyglutarate (D-2HG) upon inhibition (SLC25A1i). Previous studies have revealed comparative effects SLC25A1i or cell-permeable D-2HG...