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.firstpage","89580"],["dc.bibliographiccitation.issue","52"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","89594"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Belharazem, Djeda"],["dc.contributor.author","Grass, Albert"],["dc.contributor.author","Paul, Cornelia"],["dc.contributor.author","Vitacolonna, Mario"],["dc.contributor.author","Schalke, Berthold"],["dc.contributor.author","Rieker, Ralf J."],["dc.contributor.author","Körner, Daniel"],["dc.contributor.author","Jungebluth, Philipp"],["dc.contributor.author","Simon-Keller, Katja"],["dc.contributor.author","Hohenberger, Peter"],["dc.contributor.author","Roessner, Eric M."],["dc.contributor.author","Wiebe, Karsten"],["dc.contributor.author","Gräter, Thomas"],["dc.contributor.author","Kyriss, Thomas"],["dc.contributor.author","Ott, German"],["dc.contributor.author","Geserick, Peter"],["dc.contributor.author","Leverkus, Martin"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Marx, Alexander"],["dc.date.accessioned","2019-12-17T11:02:35Z"],["dc.date.accessioned","2021-10-27T13:21:59Z"],["dc.date.available","2019-12-17T11:02:35Z"],["dc.date.available","2021-10-27T13:21:59Z"],["dc.date.issued","2017"],["dc.description.abstract","The anti-apoptotic cellular FLICE-like inhibitory protein cFLIP plays a pivotal role in normal tissues homoeostasis and the development of many tumors, but its role in normal thymus (NT), thymomas and thymic carcinomas (TC) is largely unknown. Expression, regulation and function of cFLIP were analyzed in biopsies of NT, thymomas, thymic squamous cell carcinomas (TSCC), thymic epithelial cells (TECs) derived thereof and in the TC line 1889c by qRT-PCR, western blot, shRNA techniques, and functional assays addressing survival, senescence and autophagy. More than 90% of thymomas and TSCCs showed increased cFLIP expression compared to NT. cFLIP expression declined with age in NTs but not in thymomas. During short term culture cFLIP expression levels declined significantly slower in neoplastic than non-neoplastic primary TECs. Down-regulation of cFLIP by shRNA or NF-κB inhibition accelerated senescence and induced autophagy and cell death in neoplastic TECs. The results suggest a role of cFLIP in the involution of normal thymus and the development of thymomas and TSCC. Since increased expression of cFLIP is a known tumor escape mechanism, it may serve as tissue-based biomarker in future clinical trials, including immune checkpoint inhibitor trials in the commonly PD-L1high thymomas and TCs."],["dc.identifier.doi","10.18632/oncotarget.15929"],["dc.identifier.eissn","1949-2553"],["dc.identifier.pmid","29163772"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17003"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92059"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","1949-2553"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.subject.ddc","610"],["dc.title","Increased cFLIP expression in thymic epithelial tumors blocks autophagy via NF-κB signalling"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["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.journal","Frontiers in Oncology"],["dc.bibliographiccitation.volume","12"],["dc.contributor.affiliation","Zhang, Xiaonan; \n1\nInstitute of Pathology and Medical Research Center, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany"],["dc.contributor.affiliation","Schalke, Berthold; \n2\nDepartment of Neurology, University of Regensburg, Regensburg, Germany"],["dc.contributor.affiliation","Kvell, Krisztian; \n3\nDepartment of Pharmaceutical Biotechnology, Faculty of Pharmacy, University of Pecs, Pecs, Hungary"],["dc.contributor.affiliation","Kriegsmann, Katharina; \n4\nDepartment of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany"],["dc.contributor.affiliation","Kriegsmann, Mark; \n5\nTranslational Lung Research Centre Heidelberg, German Centre for Lung Research, Heidelberg, Germany"],["dc.contributor.affiliation","Graeter, Thomas; \n7\nDepartment of Thoracic Surgery, University Medical Centre Erlangen, Erlangen, Germany"],["dc.contributor.affiliation","Preissler, Gerhard; \n8\nDepartment of Thoraxic Surgery, Clinic Schillerhöhe, Robert-Bosch-Hospital, Gerlingen, Löwenstein, Germany"],["dc.contributor.affiliation","Ott, German; \n9\nDepartment of Clinical Pathology, Robert-Bosch-Hospital, Stuttgart, Germany"],["dc.contributor.affiliation","Kurz, Katrin; \n9\nDepartment of Clinical Pathology, Robert-Bosch-Hospital, Stuttgart, Germany"],["dc.contributor.affiliation","Bulut, Elena; \n11\nDepartment of Thoraxic Surgery, Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany"],["dc.contributor.affiliation","Ströbel, Philipp; \n12\nInstitute of Pathology, University Medical Center Göttingen, University of Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Marx, Alexander; \n1\nInstitute of Pathology and Medical Research Center, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany"],["dc.contributor.affiliation","Belharazem, Djeda; \n1\nInstitute of Pathology and Medical Research Center, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany"],["dc.contributor.author","Zhang, Xiaonan"],["dc.contributor.author","Schalke, Berthold"],["dc.contributor.author","Kvell, Krisztian"],["dc.contributor.author","Kriegsmann, Katharina"],["dc.contributor.author","Kriegsmann, Mark"],["dc.contributor.author","Graeter, Thomas"],["dc.contributor.author","Preissler, Gerhard"],["dc.contributor.author","Ott, German"],["dc.contributor.author","Kurz, Katrin"],["dc.contributor.author","Bulut, Elena"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Belharazem, Djeda"],["dc.date.accessioned","2022-08-12T11:54:07Z"],["dc.date.available","2022-08-12T11:54:07Z"],["dc.date.issued","2022-07-29"],["dc.date.updated","2022-08-12T11:08:41Z"],["dc.description.abstract","Background\r\nWNT4-driven non-canonical signaling is crucial for homeostasis and age-related involution of the thymus. Abnormal WNT signaling is important in many cancers, but the role of WNT signaling in thymic tumors is largely unknown.\r\n\r\n\r\nMaterials & MethodsExpression and function of WNT4 and FZD6 were analyzed using qRT–PCR, Western blot, ELISA, in biopsies of non-neoplastic thymi (NT), thymoma and thymic carcinomas. ShRNA techniques and functional assays were used in primary thymic epithelial cells (pTECs) and TC cell line 1889c. Cells were conventionally (2D) grown and in three-dimensional (3D) spheroids.\r\n\r\n\r\nResults\r\nIn biopsy, WHO classified B3 thymomas and TCs showed increased WNT4 expression compared with NTs. During short-term 2D culture, WNT4 expression and secretion declined in neoplastic pTECs but not in 3D spheroids or medium supplemented with recombinant WNT4 cultures. Under the latter condition, the growth of pTECs was accompanied by increased expression of non-canonical targets RAC1 and JNK. Down-regulation of WNT4 by shRNA induced cell death in pTECs derived from B3 thymomas and led to decreased RAC1, but not JNK protein phosphorylation. Pharmacological inhibition of NF-κB decreased both RAC1 and JNK phosphorylation in neoplastic pTECs.\r\n\r\n\r\nConclusions\r\nLack of the age-related decline of non-canonical WNT4 expression in TETs and restoration of declining WNT4 expression through exogeneous WNT4 or 3D culture of pTECs hints at an oncogenic role of WNT4 in TETs and is compatible with the WNT4 autocrine loop model. Crosstalk between WNT4 and NF-κB signaling may present a promising target for combined interventions in TETs."],["dc.identifier.doi","10.3389/fonc.2022.920871"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112717"],["dc.language.iso","en"],["dc.relation.eissn","2234-943X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","http://creativecommons.org/licenses/by/4.0/"],["dc.title","WNT4 overexpression and secretion in thymic epithelial tumors drive an autocrine loop in tumor cells in vitro"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","300"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","BMC Medicine"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Müller, Denise"],["dc.contributor.author","Mazzeo, Paolo"],["dc.contributor.author","Koch, Raphael"],["dc.contributor.author","Bösherz, Mark-Sebastian"],["dc.contributor.author","Welter, Stefan"],["dc.contributor.author","von Hammerstein-Equord, Alexander"],["dc.contributor.author","Hinterthaner, Marc"],["dc.contributor.author","Cordes, Lucia"],["dc.contributor.author","Belharazem, Djeda"],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Küffer, Stefan"],["dc.date.accessioned","2021-11-25T11:03:44Z"],["dc.date.accessioned","2022-08-18T12:36:39Z"],["dc.date.available","2021-11-25T11:03:44Z"],["dc.date.available","2022-08-18T12:36:39Z"],["dc.date.issued","2021-11-16"],["dc.date.updated","2022-07-29T12:17:26Z"],["dc.description.abstract","Background Multi-omics studies have shown a high and lack of common driver mutations in most thymomas (TH) and thymic carcinomas (TC) that hamper the development of novel treatment approaches. However, deregulation of apoptosis has been proposed as a common hallmark of TH and TC. BH3 profiling can be utilized to study the readiness of living cancer cells to undergo apoptosis and their dependency on pro-survival BCL-2 family proteins. Methods We screened a cohort of 62 TH and TC patient samples for expression of BCL-2 family proteins and used the TC cell line 1889c and native TH for dynamic BH3 profiling and treatment with BH3 mimetics. Results Immunohistochemical overexpression of MCL-1 and BCL-xL was a strong prognostic marker of TH and TC, and BH3 profiling indicated a strong dependency on MCL-1 and BCL-xL in TH. Single inhibition of MCL-1 resulted in increased binding of BIM to BCL-xL as an escape mechanism that the combined inhibition of both factors could overcome. Indeed, the inhibition of MCL-1 and BCL-xL in combination induced apoptosis in a caspase-dependent manner in untreated and MCL-1-resistant 1889c cells. Conclusion TH and TC are exquisitely dependent on the pro-survival factors MCL-1 and BCL-xL, making them ideal candidates for co-inhibition by BH3 mimetics. Since TH show a heterogeneous dependency on BCL-2 family proteins, upfront BH3 profiling could select patients and tailor the optimal therapy with the least possible toxicity."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.citation","BMC Medicine. 2021 Nov 16;19(1):300"],["dc.identifier.doi","10.1186/s12916-021-02158-3"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/93525"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112954"],["dc.language.iso","en"],["dc.publisher","BioMed Central"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.subject","MCL-1"],["dc.subject","BCL-xL"],["dc.subject","BH3 mimetics"],["dc.subject","Thymoma"],["dc.subject","Thymic carcinoma"],["dc.title","Functional apoptosis profiling identifies MCL-1 and BCL-xL as prognostic markers and therapeutic targets in advanced thymomas and thymic carcinomas"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["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.artnumber","1564"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Cancers"],["dc.bibliographiccitation.volume","14"],["dc.contributor.affiliation","Alwahsh, Mohammad; 1Leibniz-Institut für Analytische Wissenschaften—ISAS-e.V., 44139 Dortmund, Germany; r.knitsch@gmx.de (R.K.); jlambert@lambertnet.de (J.L.); roland.hergenroeder@isas.de (R.H.)"],["dc.contributor.affiliation","Knitsch, Robert; 1Leibniz-Institut für Analytische Wissenschaften—ISAS-e.V., 44139 Dortmund, Germany; r.knitsch@gmx.de (R.K.); jlambert@lambertnet.de (J.L.); roland.hergenroeder@isas.de (R.H.)"],["dc.contributor.affiliation","Marchan, Rosemarie; 4Department of Toxicology, Leibniz Research Center for Working Environment and Human Factors at the TU Dortmund (IfADo), 44139 Dortmund, Germany; marchan@ifado.de"],["dc.contributor.affiliation","Lambert, Jörg; 1Leibniz-Institut für Analytische Wissenschaften—ISAS-e.V., 44139 Dortmund, Germany; r.knitsch@gmx.de (R.K.); jlambert@lambertnet.de (J.L.); roland.hergenroeder@isas.de (R.H.)"],["dc.contributor.affiliation","Hoerner, Christian; 2Institute of Pathology and Medical Research Center (ZMF), University Medical Center Mannheim, Heidelberg University, 68167 Mannheim, Germany; christian.hoerner@umm.de (C.H.); dr_zhangxn@outlook.com (X.Z.); zhihan.yao@medma.uni-heidelberg.de (Z.Y.); alexander.marx@umm.de (A.M.)"],["dc.contributor.affiliation","Zhang, Xiaonan; 2Institute of Pathology and Medical Research Center (ZMF), University Medical Center Mannheim, Heidelberg University, 68167 Mannheim, Germany; christian.hoerner@umm.de (C.H.); dr_zhangxn@outlook.com (X.Z.); zhihan.yao@medma.uni-heidelberg.de (Z.Y.); alexander.marx@umm.de (A.M.)"],["dc.contributor.affiliation","Schalke, Berthold; 5Department of Neurology, University of Regensburg, 93053 Regensburg, Germany; berthold.schalke@medbo.de (B.S.); de-hyung.lee@medbo.de (D.-H.L.)"],["dc.contributor.affiliation","Lee, De-Hyung; 5Department of Neurology, University of Regensburg, 93053 Regensburg, Germany; berthold.schalke@medbo.de (B.S.); de-hyung.lee@medbo.de (D.-H.L.)"],["dc.contributor.affiliation","Bulut, Elena; 6Department of Thoracic Surgery, Thoraxklinik at Heidelberg University Hospital, 69120 Heidelberg, Germany; elena.bulut@med.uni-heidelberg.de"],["dc.contributor.affiliation","Graeter, Thomas; 7Thoracic Surgery, Clinic Löwenstein, 74245 Löwenstein, Germany; thomas.graeter@klinik-loewenstein.de"],["dc.contributor.affiliation","Ott, German; 8Department of Clinical Pathology, Robert-Bosch-Krankenhaus and Dr. Margarete-Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, Germany; german.ott@rbk.de (G.O.); katrin.kurz@rbk.de (K.S.K.)"],["dc.contributor.affiliation","Kurz, Katrin S.; 8Department of Clinical Pathology, Robert-Bosch-Krankenhaus and Dr. Margarete-Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, Germany; german.ott@rbk.de (G.O.); katrin.kurz@rbk.de (K.S.K.)"],["dc.contributor.affiliation","Preissler, Gerhard; 9Department of Thoracic Surgery, RBK Lungenzentrum Stuttgart, Robert Bosch Hospital, Clinic Schillerhoehe, 70839 Gerlingen, Germany; gerhard.preissler@rbk.de"],["dc.contributor.affiliation","Schölch, Sebastian; 11JCCU Translational Surgical Oncology (A430), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; sebastian.schoelch@umm.de"],["dc.contributor.affiliation","Farhat, Joviana; 14Department of Pharmacy, Faculty of Pharmacy, Al Ain University, Abu Dhabi P.O. Box 122612, United Arab Emirates; joviana.farhat@aau.ac.ae"],["dc.contributor.affiliation","Yao, Zhihan; 2Institute of Pathology and Medical Research Center (ZMF), University Medical Center Mannheim, Heidelberg University, 68167 Mannheim, Germany; christian.hoerner@umm.de (C.H.); dr_zhangxn@outlook.com (X.Z.); zhihan.yao@medma.uni-heidelberg.de (Z.Y.); alexander.marx@umm.de (A.M.)"],["dc.contributor.affiliation","Sticht, Carsten; 15NGS Core Facility, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; carsten.sticht@medma.uni-heidelberg.de"],["dc.contributor.affiliation","Ströbel, Philipp; 16Institute of Pathology, University Medical Center Göttingen, University of Göttingen, 37075 Göttingen, Germany; philipp.stroebel@med.uni-goettingen.de"],["dc.contributor.affiliation","Hergenröder, Roland; 1Leibniz-Institut für Analytische Wissenschaften—ISAS-e.V., 44139 Dortmund, Germany; r.knitsch@gmx.de (R.K.); jlambert@lambertnet.de (J.L.); roland.hergenroeder@isas.de (R.H.)"],["dc.contributor.affiliation","Marx, Alexander; 2Institute of Pathology and Medical Research Center (ZMF), University Medical Center Mannheim, Heidelberg University, 68167 Mannheim, Germany; christian.hoerner@umm.de (C.H.); dr_zhangxn@outlook.com (X.Z.); zhihan.yao@medma.uni-heidelberg.de (Z.Y.); alexander.marx@umm.de (A.M.)"],["dc.contributor.affiliation","Belharazem, Djeda; 2Institute of Pathology and Medical Research Center (ZMF), University Medical Center Mannheim, Heidelberg University, 68167 Mannheim, Germany; christian.hoerner@umm.de (C.H.); dr_zhangxn@outlook.com (X.Z.); zhihan.yao@medma.uni-heidelberg.de (Z.Y.); alexander.marx@umm.de (A.M.)"],["dc.contributor.author","Alwahsh, Mohammad"],["dc.contributor.author","Knitsch, Robert"],["dc.contributor.author","Marchan, Rosemarie"],["dc.contributor.author","Lambert, Jörg"],["dc.contributor.author","Hoerner, Christian"],["dc.contributor.author","Zhang, Xiaonan"],["dc.contributor.author","Schalke, Berthold"],["dc.contributor.author","Lee, De-Hyung"],["dc.contributor.author","Bulut, Elena"],["dc.contributor.author","Graeter, Thomas"],["dc.contributor.author","Belharazem, Djeda"],["dc.contributor.author","Ott, German"],["dc.contributor.author","Kurz, Katrin S."],["dc.contributor.author","Preissler, Gerhard"],["dc.contributor.author","Schölch, Sebastian"],["dc.contributor.author","Farhat, Joviana"],["dc.contributor.author","Yao, Zhihan"],["dc.contributor.author","Sticht, Carsten"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Hergenröder, Roland"],["dc.contributor.author","Marx, Alexander"],["dc.date.accessioned","2022-04-01T10:02:05Z"],["dc.date.available","2022-04-01T10:02:05Z"],["dc.date.issued","2022"],["dc.date.updated","2022-04-08T08:44:06Z"],["dc.description.abstract","Thymomas and thymic carcinomas (TC) are malignant thymic epithelial tumors (TETs) with poor outcome, if non-resectable. Metabolic signatures of TETs have not yet been studied and may offer new therapeutic options. Metabolic profiles of snap-frozen thymomas (WHO types A, AB, B1, B2, B3, n = 12) and TCs (n = 3) were determined by high resolution magic angle spinning 1H nuclear magnetic resonance (HRMAS 1H-NMR) spectroscopy. Metabolite-based prediction of active KEGG metabolic pathways was achieved with MetPA. In relation to metabolite-based metabolic pathways, gene expression signatures of TETs (n = 115) were investigated in the public “The Cancer Genome Atlas” (TCGA) dataset using gene set enrichment analysis. Overall, thirty-seven metabolites were quantified in TETs, including acetylcholine that was not previously detected in other non-endocrine cancers. Metabolite-based cluster analysis distinguished clinically indolent (A, AB, B1) and aggressive TETs (B2, B3, TCs). Using MetPA, six KEGG metabolic pathways were predicted to be activated, including proline/arginine, glycolysis and glutathione pathways. The activated pathways as predicted by metabolite-profiling were generally enriched transcriptionally in the independent TCGA dataset. Shared high lactic acid and glutamine levels, together with associated gene expression signatures suggested a strong “Warburg effect”, glutaminolysis and redox homeostasis as potential vulnerabilities that need validation in a large, independent cohort of aggressive TETs. If confirmed, targeting metabolic pathways may eventually prove as adjunct therapeutic options in TETs, since the metabolic features identified here are known to confer resistance to cisplatin-based chemotherapy, kinase inhibitors and immune checkpoint blockers, i.e., currently used therapies for non-resectable TETs."],["dc.identifier.doi","10.3390/cancers14061564"],["dc.identifier.pii","cancers14061564"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105818"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation.eissn","2072-6694"],["dc.rights","CC BY 4.0"],["dc.title","Metabolic Profiling of Thymic Epithelial Tumors Hints to a Strong Warburg Effect, Glutaminolysis and Precarious Redox Homeostasis as Potential Therapeutic Targets"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","unpublished"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","316"],["dc.bibliographiccitation.journal","Frontiers in Oncology"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Huang, Bei"],["dc.contributor.author","Belharazem, Djeda"],["dc.contributor.author","Li, Li"],["dc.contributor.author","Kneitz, Susanne"],["dc.contributor.author","Schnabel, Philipp A."],["dc.contributor.author","Rieker, Ralf J."],["dc.contributor.author","Körner, Daniel"],["dc.contributor.author","Nix, Wilfred"],["dc.contributor.author","Schalke, Berthold"],["dc.contributor.author","Müller-Hermelink, Hans Konrad"],["dc.contributor.author","Ott, German"],["dc.contributor.author","Rosenwald, Andreas"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Marx, Alexander"],["dc.date.accessioned","2019-07-09T11:40:08Z"],["dc.date.available","2019-07-09T11:40:08Z"],["dc.date.issued","2013"],["dc.description.abstract","The molecular pathogenesis of thymomas and thymic carcinomas (TCs) is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and TCs, suggesting that other oncogenic principles might be important. This made us re-analyze historic expression data obtained in a spectrum of thymomas and thymic squamous cell carcinomas (TSCCs) with a custom-made cDNA microarray. By cluster analysis, different anti-apoptotic signatures were detected in type B3 thymoma and TSCC, including overexpression of BIRC3 in TSCCs. This was confirmed by qRT-PCR in the original and an independent validation set of tumors. In contrast to several other cancer cell lines, the BIRC3-positive TSCC cell line, 1889c showed spontaneous apoptosis after BIRC3 knock-down. Targeting apoptosis genes is worth testing as therapeutic principle in TSCC."],["dc.identifier.doi","10.3389/fonc.2013.00316"],["dc.identifier.fs","603329"],["dc.identifier.pmid","24427739"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10689"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58099"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2234-943X"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Anti-Apoptotic Signature in Thymic Squamous Cell Carcinomas - Functional Relevance of Anti-Apoptotic BIRC3 Expression in the Thymic Carcinoma Cell Line 1889c."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["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"]]