5 results on '"Coch, Christoph"'
Search Results
2. PrImary decompressive Craniectomy in AneurySmal Subarachnoid hemOrrhage (PICASSO) trial: study protocol for a randomized controlled trial
- Author
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Güresir, Erdem, Lampmann, Tim, Brandecker, Simon, Czabanka, Marcus, Fimmers, Rolf, Gempt, Jens, Haas, Patrick, Haj, Amer, Jabbarli, Ramazan, Kalasauskas, Darius, König, Ralph, Mielke, Dorothee, Németh, Robert, Oppong, Marvin Darkwah, Pala, Andrej, Prinz, Vincent, Ringel, Florian, Roder, Constantin, Rohde, Veit, Schebesch, Karl-Michael, Wagner, Arthur, Coch, Christoph, and Vatter, Hartmut
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- 2022
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3. Innate immune receptor signaling induces transient melanoma dedifferentiation while preserving immunogenicity
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Thier, Beatrice, Zhao, Fang, Stupia, Simone, Brüggemann, Alicia, Koch, Johannes, Schulze, Nina, Horn, Susanne, Coch, Christoph, Hartmann, Gunter, Sucker, Antje, Schadendorf, Dirk, Paschen, Annette, Thier, Beatrice, Zhao, Fang, Stupia, Simone, Brüggemann, Alicia, Koch, Johannes, Schulze, Nina, Horn, Susanne, Coch, Christoph, Hartmann, Gunter, Sucker, Antje, Schadendorf, Dirk, and Paschen, Annette
- Abstract
Background Immune-stimulatory agents, like agonists of the innate immune receptor RIG-I, are currently tested in clinical trials as an intratumoral treatment option for patients with unresectable melanoma, aiming to enhance anti-tumor T cell responses. Switching of melanoma toward a dedifferentiated cell state has recently been linked to T cell and therapy resistance. It remains to be determined whether RIG-I agonists affect melanoma differentiation, potentially leading to T cell resistance. Methods Patient metastases-derived melanoma cell lines were treated with the synthetic RIG-I agonist 3pRNA, and effects on tumor cell survival, phenotype and differentiation were determined. Transcriptomic data sets from cell lines and metastases were analyzed for associations between RIG-I (DDX58) and melanoma differentiation markers and used to define signaling pathways involved in RIG-I- driven dedifferentiation. The impact of 3pRNA-induced melanoma dedifferentiation on CD8 T cell activation was studied in autologous tumor T cell models. Results RIG-I activation by 3pRNA induced apoptosis in a subpopulation of melanoma cells, while the majority of tumor cells switched into a non-proliferative cell state. Those persisters displayed a dedifferentiated cell phenotype, marked by downregulation of the melanocytic lineage transcription factor MITF and its target genes, including melanoma differentiation antigens (MDA). Transition into the MITFlow/MDAlow cell state was JAK-dependent, with some cells acquiring nerve growth factor receptor expression. MITFlow/MDAlow persisters switched back to the proliferative differentiated cell state when RIG-I signaling declined. Consistent with our in vitro findings, an association between melanoma dedifferentiation and high RIG-I (DDX58) levels was detected in transcriptomic data from patient metastases. Notably, despite their dedifferentiated cell phenotype, 3pRNA-induced MITFlow/ MDAlow persisters were still efficiently targeted by autologous
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- 2022
4. Individualized versus standardized risk assessment in patients at high risk for adverse drug reactions (IDrug) - study protocol for a pragmatic randomized controlled trial.
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Stingl, Julia Carolin, Kaumanns, Katharina Luise, Claus, Katrin, Lehmann, Marie-Louise, Kastenmüller, Kathrin, Bleckwenn, Markus, Hartmann, Gunther, Steffens, Michael, Wirtz, Dorothee, Leuchs, Ann-Kristin, Benda, Norbert, Meier, Florian, Schöffski, Oliver, Holdenrieder, Stefan, Coch, Christoph, and Weckbecker, Klaus
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THROMBOEMBOLISM risk factors ,HEMORRHAGE risk factors ,DRUG therapy ,WARFARIN ,DRUG side effects ,CONFIDENCE intervals ,DISEASES ,DRUG labeling ,CLINICAL drug trials ,FAMILY medicine ,PATIENT aftercare ,KIDNEY diseases ,MEDICAL needs assessment ,RESEARCH protocols ,PATIENT education ,PHARMACOLOGY ,RISK assessment ,EVIDENCE-based medicine ,DATA analysis ,RANDOMIZED controlled trials ,POLYPHARMACY - Abstract
Background: Elderly patients are particularly vulnerable to adverse drug reactions, especially if they are affected by additional risk factors such as multimorbidity, polypharmacy, impaired renal function and intake of drugs with high risk potential. Apart from these clinical parameters, drug safety and efficacy can be influenced by pharmacogenetic factors. Evidence-based recommendations concerning drug-gene-combinations have been issued by international consortia and in drug labels. However, clinical benefit of providing information on individual patient factors in a comprehensive risk assessment aiming to reduce the occurrence and severity of adverse drug reactions is not evident. Purpose of this randomized controlled trial is to compare the effect of a concise individual risk information leaflet with standard information on risk factors for side effects. Methods/Design: The trial was designed as a prospective, two-arm, randomized, controlled, multicenter, pragmatic study. 960 elderly, multimorbid outpatients in general medicine are included if they take at least one high risk and one other long-term drug (polymedication). As high risk "index drugs" oral anticoagulants and antiplatelets were chosen because of their specific, objectively assessable side effects. Following randomization, test group patients receive an individualized risk assessment leaflet evaluating their personal data concerning bleeding- and thromboembolic-risk-scores, potential drug-drug-interactions, age, renal function and pharmacogenetic factors. Control group patients obtain a standardized leaflet only containing general information on these criteria. Follow-up period is 9 months for each patient. Primary endpoint is the occurrence of a thromboembolic/bleeding event or death. Secondary endpoints are other adverse drug reactions, hospital admissions, specialist referrals and medication changes due to adverse drug reactions, the patients' adherence to medication regimen as well as health related quality of life, mortality and resulting costs. Discussion: Despite extensive evidence of risk factors for adverse drug reactions, there are few prospective trial data about an individualized risk assessment including pharmacogenetic information to increase patient safety. By conducting a health economic analysis, we will evaluate if the application of an individualized drug therapy in daily routine is cost-effective. [ABSTRACT FROM AUTHOR]
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- 2016
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5. Immune- and miRNA-response to recombinant interferon beta-1a: a biomarker evaluation study to guide the development of novel type I interferon- based therapies.
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Coenen, Martin, Hinze, Annette Viktoria, Mengel, Martin, Fuhrmann, Christine, Lüdenbach, Bastian, Zimmermann, Julian, Dykstra, Verena, Fimmers, Rolf, Viviani, Roberto, Stingl, Julia, Holdenrieder, Stefan, Müller, Marcus, Hartmann, Gunther, and Coch, Christoph
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MICRORNA ,IMMUNE response ,INTERFERON beta-1a ,BIOMARKERS ,TYPE I interferons ,TUMOR growth ,ANTIVIRAL agents - Abstract
Background: The innate immune receptor RIG-I detects viral RNA within the cytosol of infected cells. Activation of RIG-I leads to the induction of antiviral cytokines, in particular type I interferon, the inhibition of a T(H)17 response as well as to the suppression of tumor growth. Therefore, RIG-I is a promising drug target for the treatment of cancer as well as multiple sclerosis. A specific ligand for RIG-I is currently in preclinical testing. The first-in-human trial will need to be carefully designed to avoid an overshooting cytokine response. Therefore, the ResI study was set up to analyze the human immune response to standard treatment with recombinant interferon-beta to establish biomarkers for safety and efficacy of the upcoming first-in-human trial investigating the RIG-I ligand. Methods/Design: ResI is a single center, prospective, open label, non-randomized phase I clinical trial. Three different cohorts (20 healthy volunteers, 20 patients with RRMS and ongoing interferon-beta treatment and 10 patients starting on interferon-beta) will receive standard interferon-beta-1a therapy for nine days. The study will be conducted according to the principles of the german medicinal products act, ICH-GCP, and the Declaration of Helsinki on the phase I unit of the Institute of Clinical Chemistry and Clinical Pharmacology and in the Department of Neurology, both University Hospital Bonn. Interferon-beta-induced cytokine levels, surface marker on immune cells, mRNA- and miRNA-expression as well as psychometric response will be investigated as target variables. Discussion: The ResI study will assess biomarkers in response to interferon-β treatment to guide the dose steps within the first-in-human trial with a newly developed RIG-I ligand. Thus, ResI is a biomarker study to enhance the safety of the clinical development of a first-in-class compound. The data can additionally be used for the development of other therapies based on type I interferon induction such as TLR ligands. Moreover, it will help to understand the interferon-beta induced immune response in a controlled in vivo setting in the human system. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
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