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Beißbarth, Tim
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Beißbarth, Tim
Official Name
Beißbarth, Tim
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Beißbarth, T.
Beißbarth, Timothy
Beissbarth, T.
Beissbarth, Tim
Beissbarth, Timothy
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2017Journal Article [["dc.bibliographiccitation.artnumber","135"],["dc.bibliographiccitation.journal","Frontiers in Oncology"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Bayerlová, Michaela"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Wolff, Alexander"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Bleckmann, Annalen"],["dc.date.accessioned","2019-07-09T11:43:27Z"],["dc.date.available","2019-07-09T11:43:27Z"],["dc.date.issued","2017"],["dc.description.abstract","Breast cancer is a heterogeneous disease and has been classified into five molecular subtypes based on gene expression profiles. Signaling processes linked to different breast cancer molecular subtypes and different clinical outcomes are still poorly understood. Aberrant regulation of Wnt signaling has been implicated in breast cancer progression. In particular Ror1/2 receptors and several other members of the non-canonical Wnt signaling pathway were associated with aggressive breast cancer behavior. However, Wnt signals are mediated via multiple complex pathways, and it is clinically important to determine which particular Wnt cascades, including their domains and targets, are deregulated in poor prognosis breast cancer. To investigate activation and outcome of the Ror2-dependent non-canonical Wnt signaling pathway, we overexpressed the Ror2 receptor in MCF-7 and MDA-MB231 breast cancer cells, stimulated the cells with its ligand Wnt5a, and we knocked-down Ror1 in MDA-MB231 cells. We measured the invasive capacity of perturbed cells to assess phenotypic changes, and mRNA was profiled to quantify gene expression changes. Differentially expressed genes were integrated into a literature-based non-canonical Wnt signaling network. The results were further used in the analysis of an independent dataset of breast cancer patients with metastasis-free survival annotation. Overexpression of the Ror2 receptor, stimulation with Wnt5a, as well as the combination of both perturbations enhanced invasiveness of MCF-7 cells. The expression-responsive targets of Ror2 overexpression in MCF-7 induced a Ror2/Wnt module of the non-canonical Wnt signaling pathway. These targets alter regulation of other pathways involved in cell remodeling processing and cell metabolism. Furthermore, the genes of the Ror2/Wnt module were assessed as a gene signature in patient gene expression data and showed an association with clinical outcome. In summary, results of this study indicate a role of a newly defined Ror2/Wnt module in breast cancer progression and present a link between Ror2 expression and increased cell invasiveness."],["dc.identifier.doi","10.3389/fonc.2017.00135"],["dc.identifier.pmid","28695110"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14538"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58892"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","2234-943X"],["dc.relation.issn","2234-943X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Ror2 Signaling and Its Relevance in Breast Cancer Progression."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC2019Journal Article [["dc.bibliographiccitation.artnumber","70"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Clinical Medicine"],["dc.bibliographiccitation.volume","8"],["dc.contributor.affiliation","Mewes, Caspar; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany,"],["dc.contributor.affiliation","Büttner, Benedikt; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany,"],["dc.contributor.affiliation","Hinz, José; \t\t \r\n\t\t Department of Anesthesiology and Intensive Care Medicine, Klinikum Region Hannover, D-30459 Hannover, Germany,"],["dc.contributor.affiliation","Alpert, Ayelet; \t\t \r\n\t\t Faculty of Medicine, Technion−Israeli Institute of Technology, 31096 Haifa, Israel,"],["dc.contributor.affiliation","Popov, Aron-Frederik; \t\t \r\n\t\t Department of Thoracic and Cardiovascular Surgery, University Medical Center, Eberhard Karls University, D-72076 Tuebingen, Germany,"],["dc.contributor.affiliation","Ghadimi, Michael; \t\t \r\n\t\t Department of General and Visceral Surgery, University Medical Center, Georg August University, D-37075 Goettingen, Germany,"],["dc.contributor.affiliation","Beissbarth, Tim; \t\t \r\n\t\t Department of Medical Bioinformatics, University Medical Center, Georg August University, D-37077 Goettingen, Germany,"],["dc.contributor.affiliation","Tzvetkov, Mladen; \t\t \r\n\t\t Department of Pharmacology, University Medical Center, Ernst-Moritz-Arndt-University, D-17487 Greifswald, Germany,"],["dc.contributor.affiliation","Jensen, Ole; \t\t \r\n\t\t Department of Clinical Pharmacology, University Medical Center, Georg August University, D-37075 Goettingen, Germany,"],["dc.contributor.affiliation","Runzheimer, Julius; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany,"],["dc.contributor.affiliation","Quintel, Michael; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany,"],["dc.contributor.affiliation","Shen-Orr, Shai; \t\t \r\n\t\t Faculty of Medicine, Technion−Israeli Institute of Technology, 31096 Haifa, Israel,"],["dc.contributor.affiliation","Bergmann, Ingo; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany,"],["dc.contributor.affiliation","Mansur, Ashham; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany,"],["dc.contributor.author","Mewes, Caspar"],["dc.contributor.author","Büttner, Benedikt"],["dc.contributor.author","Hinz, José Maria"],["dc.contributor.author","Alpert, Ayelet"],["dc.contributor.author","Popov, Aron-Frederik"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Tzvetkov, Mladen Vassilev"],["dc.contributor.author","Jensen, Ole"],["dc.contributor.author","Runzheimer, Julius"],["dc.contributor.author","Quintel, Michael I."],["dc.contributor.author","Shen-Orr, Shai"],["dc.contributor.author","Bergmann, Ingo"],["dc.contributor.author","Mansur, Ashham"],["dc.date.accessioned","2019-07-09T11:49:58Z"],["dc.date.available","2019-07-09T11:49:58Z"],["dc.date.issued","2019"],["dc.date.updated","2022-02-09T13:23:19Z"],["dc.description.abstract","Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is a coinhibitory checkpoint protein expressed on the surface of T cells. A recent study by our working group revealed that the rs231775 single nucleotide polymorphism (SNP) in the CTLA-4 gene was associated with the survival of patients with sepsis and served as an independent prognostic variable. To further investigate the impact of CTLA-4 genetic variants on sepsis survival, we examined the effect of two functional SNPs, CTLA-4 rs733618 and CTLA-4 rs3087243, and inferred haplotypes, on the survival of 644 prospectively enrolled septic patients. Kaplan⁻Meier survival analysis revealed significantly lower 90-day mortality for rs3087243 G allele carriers (n = 502) than for AA-homozygous (n = 142) patients (27.3% vs. 40.8%, p = 0.0024). Likewise, lower 90-day mortality was observed for TAA haplotype-negative patients (n = 197; compound rs733618 T/rs231775 A/rs3087243 A) than for patients carrying the TAA haplotype (n = 447; 24.4% vs. 32.9%, p = 0.0265). Carrying the rs3087243 G allele hazard ratio (HR): 0.667; 95% confidence interval (CI): 0.489⁻0.909; p = 0.0103) or not carrying the TAA haplotype (HR: 0.685; 95% CI: 0.491⁻0.956; p = 0.0262) remained significant covariates for 90-day survival in the multivariate Cox regression analysis and thus served as independent prognostic variables. In conclusion, our findings underscore the significance of CTLA-4 genetic variants as predictors of survival of patients with sepsis."],["dc.description.sponsorship","Volkswagen Foundation"],["dc.identifier.doi","10.3390/jcm8010070"],["dc.identifier.eissn","2077-0383"],["dc.identifier.pmid","30634576"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15817"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59664"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","MDPI"],["dc.relation.eissn","2077-0383"],["dc.relation.issn","2077-0383"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","CTLA-4 Genetic Variants Predict Survival in Patients with Sepsis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC2012Journal Article [["dc.bibliographiccitation.artnumber","14"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","GMS Zeitschrift für medizinische Ausbildung"],["dc.bibliographiccitation.lastpage","14"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Raupach, Tobias"],["dc.contributor.author","Schiekirka, Sarah"],["dc.contributor.author","Münscher, Christian"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Himmel, Wolfgang"],["dc.contributor.author","Burckhardt, Gerhard"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2019-07-10T08:14:07Z"],["dc.date.available","2019-07-10T08:14:07Z"],["dc.date.issued","2012"],["dc.description.abstract","Zielsetzung: Aktuell werden an den deutschen medizinischen Fakultäten unterschiedliche Konzepte zur leistungsorientierten Mittelvergabe (LOM)in der Lehre diskutiert. Die Umsetzung scheitert mitunter am Mangel valider Messkriterien zur Beurteilung der Lehrqualität. Neben der Struktur und den Prozessen der Lehre sollte das Ergebnis der Lehre im Mittelpunkt der Qualitätsbewertung stehen. Ziele dieser Arbeit waren die Erprobung eines neuen, lernzielbezogenen Evaluationssystems im klinischen Abschnitt des Studiums der Humanmedizin und der Vergleich der Ergebnisse mit den Daten eines traditionellen Evaluationsverfahrens. Methodik: Aus studentischen Selbsteinschätzungen zu Beginn und Ende eines jeden Lehrmoduls wurde nach einer neu entwickelten Formel der lernzielbezogene, prozentuale Lernerfolg berechnet. Die Lernerfolgs- Mittelwerte pro Modul wurden mit traditionellen Evaluationsparametern, insbesondere mit Globalbewertungen, ins Verhältnis gesetzt. Ergebnisse: Der mittels vergleichender Selbsteinschätzungen berechnete Lernerfolg und die Globalbewertungen produzierten deutlich unterschiedliche Rangfolgen der 21 klinischen Module. Zwischen dem Lernerfolg und den Globalbewertungen fand sich keine statistisch signifikante Korrelation. Allerdings korrelierten die Globalbewertungen stark mit den studentischen Erwartungen vor Modulbeginn und mit strukturellen und prozeduralen Parametern der Lehre (Pearson’s r zwischen 0,7 und 0,9). Schlussfolgerung: Die Messung des Lernzuwachses mittels vergleichender studentischer Selbsteinschätzungen kann die traditionelle Evaluation um eine wichtige Dimension erweitern. Im Unterschied zu studentischen Globalbewertungen ist das neue Instrument lernzielbezogen und unabhängiger vom Einfluss Konstrukt-irrelevanter Parameter. Hinsichtlich der Entwicklung eines LOM-Algorithmus eignet sich das neue Instrument gut zur Beurteilung der Lehrqualität."],["dc.identifier.fs","591967"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9538"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61439"],["dc.language.iso","de"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1860-3572"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Implementierung und Erprobung eines Lernziel-basierten Evaluationssystems im Studium der Humanmedizin"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details2018Journal Article [["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Mewes, Caspar"],["dc.contributor.author","Büttner, Benedikt"],["dc.contributor.author","Hinz, José Maria"],["dc.contributor.author","Alpert, Ayelet"],["dc.contributor.author","Popov, Aron-Frederik"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Tzvetkov, Mladen Vassilev"],["dc.contributor.author","Shen-Orr, Shai"],["dc.contributor.author","Bergmann, Ingo"],["dc.contributor.author","Mansur, Ashham"],["dc.date.accessioned","2019-07-09T11:45:59Z"],["dc.date.available","2019-07-09T11:45:59Z"],["dc.date.issued","2018"],["dc.description.abstract","Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a surface protein on T cells, that has an inhibitory effect on the host immune reaction and prevents overreaction of the immune system. Because the functional single-nucleotide polymorphism (SNP) rs231775 of the CTLA-4 gene is associated with autoimmune diseases and because of the critical role of the immune reaction in sepsis, we intended to examine the effect of this polymorphism on survival in patients with sepsis. 644 septic adult Caucasian patients were prospectively enrolled in this study. Patients were followed up for 90 days. Mortality risk within this period was defined as primary outcome parameter. Kaplan-Meier survival analysis revealed a significantly lower 90-day mortality risk among GG homozygous patients (n = 101) than among A allele carriers (n = 543; 22% and 32%, respectively; p = 0.03565). Furthermore, the CTLA-4 rs231775 GG genotype remained a significant covariate for 90-day mortality risk after controlling for confounders in the multivariate Cox regression analysis (hazard ratio: 0.624; 95% CI: 0.399–0.975; p = 0.03858). In conclusion, our study provides the first evidence for CTLA-4 rs231775 as a prognostic variable for the survival of patients with sepsis and emphasizes the need for further research to reveal potential functional associations between CTLA-4 and the immune pathophysiology of sepsis."],["dc.identifier.doi","10.1038/s41598-018-33246-9"],["dc.identifier.pmid","30310101"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15369"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59355"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","The CTLA-4 rs231775 GG genotype is associated with favorable 90-day survival in Caucasian patients with sepsis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC2018Journal Article [["dc.bibliographiccitation.firstpage","18"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Genome Medicine"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Perera-Bel, Júlia"],["dc.contributor.author","Hutter, Barbara"],["dc.contributor.author","Heining, Christoph"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Fröhlich, Martina"],["dc.contributor.author","Fröhling, Stefan"],["dc.contributor.author","Glimm, Hanno"],["dc.contributor.author","Brors, Benedikt"],["dc.contributor.author","Beißbarth, Tim"],["dc.date.accessioned","2019-01-25T08:41:44Z"],["dc.date.available","2019-01-25T08:41:44Z"],["dc.date.issued","2018"],["dc.description.abstract","A comprehensive understanding of cancer has been furthered with technological improvements and decreasing costs of next-generation sequencing (NGS). However, the complexity of interpreting genomic data is hindering the implementation of high-throughput technologies in the clinical context: increasing evidence on gene-drug interactions complicates the task of assigning clinical significance to genomic variants."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2018"],["dc.identifier.doi","10.1186/s13073-018-0529-2"],["dc.identifier.pmid","29544535"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15160"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57380"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","In goescholar not merged with http://resolver.sub.uni-goettingen.de/purl?gs-1/15091 but duplicate"],["dc.notes.status","zu prüfen"],["dc.relation.eissn","1756-994X"],["dc.rights","CC BY 4.0"],["dc.rights.access","openAccess"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","From somatic variants towards precision oncology: Evidence-driven reporting of treatment options in molecular tumor boards"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC2018Journal Article [["dc.bibliographiccitation.artnumber","e453"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Experimental & Molecular Medicine"],["dc.bibliographiccitation.volume","50"],["dc.contributor.author","Apweiler, Rolf"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Berthold, Michael R."],["dc.contributor.author","Blüthgen, Nils"],["dc.contributor.author","Burmeister, Yvonne"],["dc.contributor.author","Dammann, Olaf"],["dc.contributor.author","Deutsch, Andreas"],["dc.contributor.author","Feuerhake, Friedrich"],["dc.contributor.author","Franke, Andre"],["dc.contributor.author","Hasenauer, Jan"],["dc.contributor.author","Hoffmann, Steve"],["dc.contributor.author","Höfer, Thomas"],["dc.contributor.author","Jansen, Peter L. M."],["dc.contributor.author","Kaderali, Lars"],["dc.contributor.author","Klingmüller, Ursula"],["dc.contributor.author","Koch, Ina"],["dc.contributor.author","Kohlbacher, Oliver"],["dc.contributor.author","Kuepfer, Lars"],["dc.contributor.author","Lammert, Frank"],["dc.contributor.author","Maier, Dieter"],["dc.contributor.author","Pfeifer, Nico"],["dc.contributor.author","Radde, Nicole"],["dc.contributor.author","Rehm, Markus"],["dc.contributor.author","Roeder, Ingo"],["dc.contributor.author","Saez-Rodriguez, Julio"],["dc.contributor.author","Sax, Ulrich"],["dc.contributor.author","Schmeck, Bernd"],["dc.contributor.author","Schuppert, Andreas"],["dc.contributor.author","Seilheimer, Bernd"],["dc.contributor.author","Theis, Fabian J."],["dc.contributor.author","Vera, Julio"],["dc.contributor.author","Wolkenhauer, Olaf"],["dc.date.accessioned","2019-07-09T11:45:27Z"],["dc.date.available","2019-07-09T11:45:27Z"],["dc.date.issued","2018"],["dc.description.abstract","New technologies to generate, store and retrieve medical and research data are inducing a rapid change in clinical and translational research and health care. Systems medicine is the interdisciplinary approach wherein physicians and clinical investigators team up with experts from biology, biostatistics, informatics, mathematics and computational modeling to develop methods to use new and stored data to the benefit of the patient. We here provide a critical assessment of the opportunities and challenges arising out of systems approaches in medicine and from this provide a definition of what systems medicine entails. Based on our analysis of current developments in medicine and healthcare and associated research needs, we emphasize the role of systems medicine as a multilevel and multidisciplinary methodological framework for informed data acquisition and interdisciplinary data analysis to extract previously inaccessible knowledge for the benefit of patients."],["dc.identifier.doi","10.1038/emm.2017.290"],["dc.identifier.pmid","29497170"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15213"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59233"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/305033/EU//CASYM"],["dc.relation","info:eu-repo/grantAgreement/EC/H2020/643271/EU//ERACoSysMed"],["dc.relation.issn","2092-6413"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Whither systems medicine?"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC2009Journal Article [["dc.bibliographiccitation.firstpage","20"],["dc.bibliographiccitation.journal","BMC systems biology"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Sahin, Özgür"],["dc.contributor.author","Fröhlich, Holger"],["dc.contributor.author","Löbke, Christian"],["dc.contributor.author","Korf, Ulrike"],["dc.contributor.author","Burmester, Sara"],["dc.contributor.author","Majety, Meher"],["dc.contributor.author","Mattern, Jens"],["dc.contributor.author","Schupp, Ingo"],["dc.contributor.author","Chaouiya, Claudine"],["dc.contributor.author","Thieffry, Denis"],["dc.contributor.author","Poustka, Annemarie"],["dc.contributor.author","Wiemann, Stefan"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Arlt, Dorit"],["dc.date.accessioned","2019-07-09T11:52:38Z"],["dc.date.available","2019-07-09T11:52:38Z"],["dc.date.issued","2009"],["dc.description.abstract","In breast cancer, overexpression of the transmembrane tyrosine kinase ERBB2 is an adverse prognostic marker, and occurs in almost 30% of the patients. For therapeutic intervention, ERBB2 is targeted by monoclonal antibody trastuzumab in adjuvant settings; however, de novo resistance to this antibody is still a serious issue, requiring the identification of additional targets to overcome resistance. In this study, we have combined computational simulations, experimental testing of simulation results, and finally reverse engineering of a protein interaction network to define potential therapeutic strategies for de novo trastuzumab resistant breast cancer."],["dc.description.abstract","First, we employed Boolean logic to model regulatory interactions and simulated single and multiple protein loss-of-functions. Then, our simulation results were tested experimentally by producing single and double knockdowns of the network components and measuring their effects on G1/S transition during cell cycle progression. Combinatorial targeting of ERBB2 and EGFR did not affect the response to trastuzumab in de novo resistant cells, which might be due to decoupling of receptor activation and cell cycle progression. Furthermore, examination of c-MYC in resistant as well as in sensitive cell lines, using a specific chemical inhibitor of c-MYC (alone or in combination with trastuzumab), demonstrated that both trastuzumab sensitive and resistant cells responded to c-MYC perturbation."],["dc.description.abstract","In this study, we connected ERBB signaling with G1/S transition of the cell cycle via two major cell signaling pathways and two key transcription factors, to model an interaction network that allows for the identification of novel targets in the treatment of trastuzumab resistant breast cancer. Applying this new strategy, we found that, in contrast to trastuzumab sensitive breast cancer cells, combinatorial targeting of ERBB receptors or of key signaling intermediates does not have potential for treatment of de novo trastuzumab resistant cells. Instead, c-MYC was identified as a novel potential target protein in breast cancer cells."],["dc.identifier.doi","10.1186/1752-0509-3-1"],["dc.identifier.pmid","19118495"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5813"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60247"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1752-0509"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.subject.mesh","Antibodies, Monoclonal"],["dc.subject.mesh","Blotting, Western"],["dc.subject.mesh","Breast Neoplasms"],["dc.subject.mesh","Cell Line, Tumor"],["dc.subject.mesh","Computer Simulation"],["dc.subject.mesh","DNA-Binding Proteins"],["dc.subject.mesh","Drug Delivery Systems"],["dc.subject.mesh","Female"],["dc.subject.mesh","G1 Phase"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Models, Biological"],["dc.subject.mesh","Protein Engineering"],["dc.subject.mesh","Receptor, Epidermal Growth Factor"],["dc.subject.mesh","Reverse Transcriptase Polymerase Chain Reaction"],["dc.subject.mesh","Signal Transduction"],["dc.subject.mesh","Transcription Factors"],["dc.title","Modeling ERBB receptor-regulated G1/S transition to find novel targets for de novo trastuzumab resistance."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC2018Journal Article [["dc.bibliographiccitation.artnumber","e0197162"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","PLOS ONE"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Wolff, Alexander"],["dc.contributor.author","Bayerlová, Michaela"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Kube, Dieter"],["dc.contributor.author","Beißbarth, Tim"],["dc.date.accessioned","2019-07-09T11:45:42Z"],["dc.date.available","2019-07-09T11:45:42Z"],["dc.date.issued","2018"],["dc.description.abstract","BACKGROUND: Pipeline comparisons for gene expression data are highly valuable for applied real data analyses, as they enable the selection of suitable analysis strategies for the dataset at hand. Such pipelines for RNA-Seq data should include mapping of reads, counting and differential gene expression analysis or preprocessing, normalization and differential gene expression in case of microarray analysis, in order to give a global insight into pipeline performances. METHODS: Four commonly used RNA-Seq pipelines (STAR/HTSeq-Count/edgeR, STAR/RSEM/edgeR, Sailfish/edgeR, TopHat2/Cufflinks/CuffDiff)) were investigated on multiple levels (alignment and counting) and cross-compared with the microarray counterpart on the level of gene expression and gene ontology enrichment. For these comparisons we generated two matched microarray and RNA-Seq datasets: Burkitt Lymphoma cell line data and rectal cancer patient data. RESULTS: The overall mapping rate of STAR was 98.98% for the cell line dataset and 98.49% for the patient dataset. Tophat's overall mapping rate was 97.02% and 96.73%, respectively, while Sailfish had only an overall mapping rate of 84.81% and 54.44%. The correlation of gene expression in microarray and RNA-Seq data was moderately worse for the patient dataset (ρ = 0.67-0.69) than for the cell line dataset (ρ = 0.87-0.88). An exception were the correlation results of Cufflinks, which were substantially lower (ρ = 0.21-0.29 and 0.34-0.53). For both datasets we identified very low numbers of differentially expressed genes using the microarray platform. For RNA-Seq we checked the agreement of differentially expressed genes identified in the different pipelines and of GO-term enrichment results. CONCLUSION: In conclusion the combination of STAR aligner with HTSeq-Count followed by STAR aligner with RSEM and Sailfish generated differentially expressed genes best suited for the dataset at hand and in agreement with most of the other transcriptomics pipelines."],["dc.identifier.doi","10.1371/journal.pone.0197162"],["dc.identifier.pmid","29768462"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15290"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59290"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.haserratum","/handle/2/63504"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.subject.mesh","Burkitt Lymphoma"],["dc.subject.mesh","Cell Line, Tumor"],["dc.subject.mesh","Gene Expression Regulation, Neoplastic"],["dc.subject.mesh","High-Throughput Nucleotide Sequencing"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Oligonucleotide Array Sequence Analysis"],["dc.subject.mesh","RNA, Neoplasm"],["dc.subject.mesh","Rectal Neoplasms"],["dc.title","A comparative study of RNA-Seq and microarray data analysis on the two examples of rectal-cancer patients and Burkitt Lymphoma cells."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC2017-08-29Journal Article [["dc.bibliographiccitation.artnumber","9887"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific reports"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Hinz, José Maria"],["dc.contributor.author","Büttner, Benedikt"],["dc.contributor.author","Kriesel, Fabian"],["dc.contributor.author","Steinau, Maximilian"],["dc.contributor.author","Popov, Aron-Frederik"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Tzvetkov, Mladen Vassilev"],["dc.contributor.author","Bergmann, Ingo"],["dc.contributor.author","Mansur, Ashham"],["dc.date.accessioned","2019-07-09T11:43:39Z"],["dc.date.available","2019-07-09T11:43:39Z"],["dc.date.issued","2017-08-29"],["dc.description.abstract","A recent genome-wide association study showed that a genetic variant within the FER gene is associated with survival in patients with sepsis due to pneumonia. Because severe pneumonia is the main cause of acute respiratory distress syndrome (ARDS), we aimed to investigate the effect of the FER polymorphism rs4957796 on the 90-day survival in patients with ARDS due to pneumonia. An assessment of a prospectively collected cohort of 441 patients with ARDS admitted to three intensive care units at the University Medical Centre identified 274 patients with ARDS due to pneumonia. The 90-day mortality risk was recorded as the primary outcome parameter. Sepsis-related organ failure assessment (SOFA) scores and organ support-free days were used as the secondary variables. FER rs4957796 TT-homozygous patients were compared with C-allele carriers. The survival analysis revealed a higher 90-day mortality risk among T homozygotes than among C-allele carriers (p = 0.0144) exclusively in patients with severe ARDS due to pneumonia. The FER rs4957796 TT genotype remained a significant covariate for the 90-day mortality risk in the multivariate analysis (hazard ratio, 4.62; 95% CI, 1.58-13.50; p = 0.0050). In conclusion, FER rs4957796 might act as a prognostic variable for survival in patients with severe ARDS due to pneumonia."],["dc.identifier.doi","10.1038/s41598-017-08540-7"],["dc.identifier.pmid","28851893"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14613"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58938"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","The FER rs4957796 TT genotype is associated with unfavorable 90-day survival in Caucasian patients with severe ARDS due to pneumonia."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC