Ströbel, Philipp

[["dc.bibliographiccitation.firstpage","894"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY"],["dc.bibliographiccitation.lastpage","905"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Belharazem, Djeda"],["dc.contributor.author","Schalke, Berthold"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Nix, Wilfred"],["dc.contributor.author","Vitacolonna, Mario"],["dc.contributor.author","Hohenberger, Peter"],["dc.contributor.author","Roessner, Eric"],["dc.contributor.author","Schulze, Torsten J."],["dc.contributor.author","Saruhan-Direskeneli, Gueher"],["dc.contributor.author","Yilmaz, Vuslat"],["dc.contributor.author","Ott, German"],["dc.contributor.author","Stroebel, Philipp"],["dc.contributor.author","Marx, Alexander"],["dc.date.accessioned","2018-11-07T09:51:57Z"],["dc.date.available","2018-11-07T09:51:57Z"],["dc.date.issued","2015"],["dc.description.abstract","Objective: The capacity of thymomas to generate mature CD4+ effector T cells from immature precursors inside the tumor and export them to the blood is associated with thymoma-associated myasthenia gravis (TAMG). Why TAMG (+) thymomas generate and export more mature CD4+ T cells than MG(-) thymomas is unknown. Methods: Unfixed thymoma tissue, thymocytes derived thereof, peripheral blood mononuclear cells (PBMCs), T-cell subsets and B cells were analysed using qRT-PCR and western blotting. Survival of PBMCs was measured by MTT assay. FAS-mediated apoptosis in PBMCs was quantified by flow cytometry. NF-kappa B in PBMCs was inhibited by the NF-kappa B-Inhibitor, EF24 prior to FAS-Ligand (FASLG) treatment for apoptosis induction. Results: Expression levels of the apoptosis inhibitor cellular FLICE-like inhibitory protein (c-FLIP) in blood T cells and intratumorous thymocytes were higher in TAMG(+) than in MG(-) thymomas and non-neoplastic thymic remnants. Thymocytes and PBMCs of TAMG patients showed nuclear NF-kappa B accumulation and apoptosis resistance to FASLG stimulation that was sensitive to NF-kappa B blockade. Thymoma removal reduced cFLIP expression in PBMCs. Interpretation: We conclude that thymomas induce cFLIP overexpression in thymocytes and their progeny, blood T cells. We suggest that the stronger cFLIP overexpression in TAMG(+) compared to MG(-) thymomas allows for the more efficient generation of mature CD4+ T cells in TAMG(+) thymomas. cFLIP overexpression in thymocytes and exported CD4+ T cells of patients with TAMG might contribute to the pathogenesis of TAMG by impairing central and peripheral T-cell tolerance."],["dc.identifier.doi","10.1002/acn3.210"],["dc.identifier.isi","000367238200003"],["dc.identifier.pmid","26401511"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36014"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","2328-9503"],["dc.title","cFLIP overexpression in T cells in thymoma-associated myasthenia gravis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","ENDOCRINE CONNECTIONS"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Belharazem, Djeda"],["dc.contributor.author","Kirchner, Matthias"],["dc.contributor.author","Geissler, Franziska"],["dc.contributor.author","Bugert, Peter"],["dc.contributor.author","Spahn, Martin"],["dc.contributor.author","Kneitz, Burkhard"],["dc.contributor.author","Riedmiller, Hubertus"],["dc.contributor.author","Sauer, Christian"],["dc.contributor.author","Kueffer, Stefan"],["dc.contributor.author","Trojan, Lutz"],["dc.contributor.author","Bolenz, Christian"],["dc.contributor.author","Michel, Maurice Stephan"],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Stroebel, Philipp"],["dc.date.accessioned","2018-11-07T09:04:21Z"],["dc.date.available","2018-11-07T09:04:21Z"],["dc.date.issued","2012"],["dc.description.abstract","Background: Insulin-like growth factor 2 (IGF2) is the predominant IGF in adults and regulates cell growth. In contrast to normal tissues, where IGF2 is imprinted and only expressed from the paternal allele, loss of imprinting (LOI) and biallelic IGF2 expression are observed in many cancers including prostate cancer (PCa). We here studied whether LOI of IGF2 in normal circulating peripheral blood lymphocytes can predict increased PCa risk. Samples and methods: We analyzed IGF2 protein levels, IGF2 820G/A genotype and imprinting status, as well as methylation status of the IGF2 imprinting control region (ICR) in 113 blood samples of patients with a history of radical prostatectomy (RPE) for PCa by ELISA, restriction-fragment length polymorphism, and bisulfite-DNA sequencing. Results were compared to 249 male blood donors with unknown prostate specific antigen (PSA) status. Results: The 820G/A genotype was enriched in the RPE group and was associated with younger age at cancer diagnosis. LOI in patients was only slightly more frequent than in controls, but IGF2 levels were significantly higher and uncoupled from the imprinting status. Analysis of the IGF2/H19 ICR revealed marked hypermethylation. Conclusions: The IGF 820G/A genotype is associated with PCa diagnosis at younger age. Increased IGF2 in patients with PCa appears to be the result of impaired imprinting in non-neoplastic cells rather than a paracrine tumor product. Uncoupling of IGF2 protein levels from imprinting status (not LOI alone) and hypermethylation of the ICR characterized PCa patients and could have the potential to indicate persons at risk in screening programs."],["dc.identifier.doi","10.1530/EC-12-0054"],["dc.identifier.isi","000209773300005"],["dc.identifier.pmid","23781309"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25099"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Bioscientifica Ltd"],["dc.relation.issn","2049-3614"],["dc.title","Relaxed imprinting of IGF2 in peripheral blood cells of patients with a history of prostate cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","101"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Virchows Archiv"],["dc.bibliographiccitation.lastpage","110"],["dc.bibliographiccitation.volume","478"],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Belharazem, Djeda"],["dc.contributor.author","Lee, De-Hyung"],["dc.contributor.author","Popovic, Zoran V."],["dc.contributor.author","Reißfelder, Christoph"],["dc.contributor.author","Schalke, Berthold"],["dc.contributor.author","Schölch, Sebastian"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Weis, Cleo-Aron"],["dc.contributor.author","Yamada, Yosuke"],["dc.date.accessioned","2021-04-14T08:29:13Z"],["dc.date.available","2021-04-14T08:29:13Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1007/s00428-021-03068-8"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82835"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1432-2307"],["dc.relation.issn","0945-6317"],["dc.title","Molecular pathology of thymomas: implications for diagnosis and therapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","693"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Histopathology"],["dc.bibliographiccitation.lastpage","703"],["dc.bibliographiccitation.volume","70"],["dc.contributor.author","Pfister, Frederick"],["dc.contributor.author","Hussain, Hussam"],["dc.contributor.author","Belharazem, Djeda"],["dc.contributor.author","Busch, Svenja"],["dc.contributor.author","Simon-Keller, Katja"],["dc.contributor.author","Becker, Dominic"],["dc.contributor.author","Pfister, Eva"],["dc.contributor.author","Rieker, Ralf J."],["dc.contributor.author","Stroebel, Philipp"],["dc.contributor.author","Marx, Alexander"],["dc.date.accessioned","2018-11-07T10:25:44Z"],["dc.date.available","2018-11-07T10:25:44Z"],["dc.date.issued","2017"],["dc.description.abstract","AimsThymomas and thymic squamous cell carcinomas (TSQCCs) are rare thymic epithelial tumours. Data on angiogenesis and vascular phenotype in these tumours are limited, and no study has taken histological World Health Organization (WHO) subtypes into account. The aim of this study was to compare vascularization, pericytes coverage and expression of angiogenic growth factors in different WHO-defined subtypes of thymoma Methods and resultsVascular density, diameter and architecture and expression of -smooth muscle actin (SMA), platelet-derived growth factor (PDGF) receptor- (PDGFR), vascular endothelial growth factor (VEGF) receptor 1 (VEGFR1) and VEGF receptor 2 (VEGFR2) were investigated in WHO type A, AB, B1, B2 and B3 thymomas and TSQCCs, by the use of immunostaining, quantitative morphometry, and tumour vessel isolation by trypsin digestion. Expression levels of angiopoietin 1 (Ang-1), angiopoietin 2 (Ang-2), VEGF-A, PDGF-B and Hif-1 were examined by quantitative reverse transcription polymerase chain reaction. A and AB thymomas were characterized by a dense network of capillary-like vessels with tight pericyte coverage, whereas B thymomas showed a loose vascular network with increasing vascular diameters and increasing expression of SMA and PDGFR from B1 to B3 thymomas and TSQCCs. VEGFR1 and VEGFR2 were expressed in vessels of all analysed tumour entities, and at higher levels in epithelial cells of A and B3 thymomas and TSQCCs. mRNA of Ang-2, but not of Ang-1, was significantly up-regulated in all thymoma subtypes, with the highest levels being found in A thymomas. In TSQCCs, Ang-1 and VEGF were the predominantly up-regulated growth factors. Hif-1 was only up-regulated in B3 thymomas and TSQCCs. ConclusionThymomas and TSQCCs differ significantly in their vascular architecture and expression of key angiogenic growth factors. The findings could help to improve the differential diagnosis of difficult-to-classify thymic epithelial tumours, and indicate different mechanisms of tumour angiogenesis and functional differences of tumour vessels of major thymoma subtypes and TSQCCs."],["dc.description.sponsorship","BMBF [01DL12027]"],["dc.identifier.doi","10.1111/his.13114"],["dc.identifier.isi","000397588600002"],["dc.identifier.pmid","27791295"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42915"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley"],["dc.relation.issn","1365-2559"],["dc.relation.issn","0309-0167"],["dc.title","Vascular architecture as a diagnostic marker for differentiation of World Health Organization thymoma subtypes and thymic carcinoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","971"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Journal of Gastroenterology"],["dc.bibliographiccitation.lastpage","984"],["dc.bibliographiccitation.volume","51"],["dc.contributor.author","Belharazem, Djeda"],["dc.contributor.author","Magdeburg, Julia"],["dc.contributor.author","Berton, Ann-Kristin"],["dc.contributor.author","Beissbarth, Li"],["dc.contributor.author","Sauer, Christian"],["dc.contributor.author","Sticht, Carsten"],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Hofheinz, Ralf"],["dc.contributor.author","Post, Stephen G."],["dc.contributor.author","Kienle, Peter"],["dc.contributor.author","Stroebel, Philipp"],["dc.date.accessioned","2018-11-07T10:07:55Z"],["dc.date.available","2018-11-07T10:07:55Z"],["dc.date.issued","2016"],["dc.description.abstract","Loss of imprinting (LOI) of the insulin-like growth factor 2 (IGF2) is an early event in the development of colorectal cancer (CRC). Whether LOI of IGF2 denotes a molecular or clinical cancer subgroup is currently unknown. Tumor biopsies and paired normal mucosa from 399 patients with extensive clinical annotations were analyzed for LOI and IGF2 expression. LOI status in 140 informative cases was correlated with clinicopathologic parameters and outcome. LOI was frequent in normal mucosa and tumors and occurred throughout the large intestine. LOI was unrelated to microsatellite instability, KRAS mutation status, stage, and survival. However, CRC with LOI showed increased IGF2 protein levels and activation of AKT1. Gene expression analysis of tumors with and without LOI and knockdown of IGF2 in cell lines revealed that IGF2 induced distinct sets of activated and repressed genes, including Wnt5a, CEACAM6, IGF2BP3, KPN2A, BRCA2, and CDK1. Inhibition of AKT1 in IGF2-stimulated cells showed that the downstream effects of IGF2 on cell proliferation and gene expression were strictly AKT1-dependent. LOI of IGF2 is a frequent and early event in CRC that occurs both in the adenomatous polyposis coli (APC) gene-mutated and serrated route of carcinogenesis. LOI leads to overexpression of IGF2, activates IGF1R and AKT1, and is a powerful driver of cell proliferation. Moreover, our results suggest that IGF2 via AKT1 also contributes to non-canonical wnt signaling. Although LOI had no significant impact on major clinical parameters and outcome, its potential as a target for preventive and therapeutic interventions merits further investigation."],["dc.identifier.doi","10.1007/s00535-016-1181-5"],["dc.identifier.isi","000385170300004"],["dc.identifier.pmid","26984550"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39375"],["dc.language.iso","en"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","1435-5922"],["dc.relation.issn","0944-1174"],["dc.title","Carcinoma of the colon and rectum with deregulation of insulin-like growth factor 2 signaling: clinical and molecular implications"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","256"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Molecular Oncology"],["dc.bibliographiccitation.lastpage","266"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Küffer, Stefan"],["dc.contributor.author","Gutting, Tobias"],["dc.contributor.author","Belharazem, Djeda"],["dc.contributor.author","Sauer, Christian"],["dc.contributor.author","Michel, Maurice S."],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Trojan, Lutz"],["dc.contributor.author","Ströbel, Philipp"],["dc.date.accessioned","2020-12-10T14:05:58Z"],["dc.date.available","2020-12-10T14:05:58Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1002/1878-0261.12164"],["dc.identifier.issn","1574-7891"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/69728"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Insulin-like growth factor 2 expression in prostate cancer is regulated by promoter-specific methylation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","55"],["dc.bibliographiccitation.journal","Experimental Neurology"],["dc.bibliographiccitation.lastpage","65"],["dc.bibliographiccitation.volume","270"],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Porubsky, Stefan"],["dc.contributor.author","Belharazem, Djeda"],["dc.contributor.author","Saruhan-Direskeneli, Guher"],["dc.contributor.author","Schalke, Berthold"],["dc.contributor.author","Stroebel, Philipp"],["dc.contributor.author","Weis, Cleo-Aron"],["dc.date.accessioned","2018-11-07T09:54:21Z"],["dc.date.available","2018-11-07T09:54:21Z"],["dc.date.issued","2015"],["dc.description.abstract","Thymoma-associated Myasthenia gravis (TAMG) is one of the anti-acetylcholine receptor MG (AChR-MG) sub-types. The clinico-pathological features of TAMG and its pathogenesis are described here in comparison with pathogenetic models suggested for the more common non-thymoma AChR-MG subtypes, early onset MG and late onset MG. Emphasis is put on the role of abnormal intratumorous T cell selection and activation, lack of intratumorous myoid cells and regulatory T cells as well as deficient expression of the autoimmune regulator (AIRE) by neoplastic thymic epithelial cells. We review spontaneous and genetically engineered thymoma models in a spectrum of animals and the extensive clinical and immunological overlap between canine, feline and human TAMG. Finally, limitations and perspectives of the transplantation of human and murine thymoma tissue into nude mice, as potential models for TAMG, are addressed. (C) 2015 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.expneurol.2015.02.010"],["dc.identifier.isi","000356563800007"],["dc.identifier.pmid","25700911"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36522"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.issn","1090-2430"],["dc.relation.issn","0014-4886"],["dc.title","Thymoma related myasthenia gravis in humans and potential animal models"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]