Ströbel, Philipp

[["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.journal","Pathology & Oncology Research"],["dc.bibliographiccitation.volume","27"],["dc.contributor.affiliation","Jain, Deepali; \r\n\r\n1\r\nDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India"],["dc.contributor.affiliation","Guleria, Prerna; \r\n\r\n1\r\nDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India"],["dc.contributor.affiliation","Singh, Varsha; \r\n\r\n1\r\nDepartment of Pathology, All India Institute of Medical Sciences, New Delhi, India"],["dc.contributor.affiliation","Parshad, Rajinder; \r\n\r\n2\r\nDepartment of Surgery, All India Institute of Medical Sciences, New Delhi, India"],["dc.contributor.affiliation","Kumar, Sunil; \r\n\r\n3\r\nSurgical Oncology, All India Institute of Medical Sciences, New Delhi, India"],["dc.contributor.affiliation","Gaiser, Timo; \r\n\r\n4\r\nInstitute of Pathology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany"],["dc.contributor.affiliation","Kurz, Katrin S.; \r\n\r\n5\r\nDr. Margarete Fischer-Bosch Institute for Clinical Pharmacology, Stuttgart, Germany"],["dc.contributor.affiliation","Ott, German; \r\n\r\n5\r\nDr. Margarete Fischer-Bosch Institute for Clinical Pharmacology, Stuttgart, Germany"],["dc.contributor.affiliation","Porubsky, Stefan; \r\n\r\n4\r\nInstitute of Pathology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany"],["dc.contributor.affiliation","Preissler, Gerhard; \r\n\r\n8\r\nDepartment of Thoracic Surgery, Schillerhöhe Clinics, Robert-Bosch-Krankenhaus, Gerlingen, Germany"],["dc.contributor.affiliation","Sauer, Christian G.; \r\n\r\n4\r\nInstitute of Pathology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany"],["dc.contributor.affiliation","Schölch, Sebastian; \r\n\r\n9\r\nDepartment of Surgery, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany"],["dc.contributor.affiliation","Ströbel, Philipp; \r\n\r\n11\r\nInstitute of Pathology, University Medical Center Göttingen, University of Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Hielscher, Thomas; \r\n\r\n12\r\nDepartment of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany"],["dc.contributor.affiliation","Marx, Alexander; \r\n\r\n4\r\nInstitute of Pathology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany"],["dc.contributor.affiliation","Popovic, Zoran V.; \r\n\r\n4\r\nInstitute of Pathology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany"],["dc.contributor.author","Jain, Deepali"],["dc.contributor.author","Guleria, Prerna"],["dc.contributor.author","Singh, Varsha"],["dc.contributor.author","Parshad, Rajinder"],["dc.contributor.author","Kumar, Sunil"],["dc.contributor.author","Gaiser, Timo"],["dc.contributor.author","Kurz, Katrin S."],["dc.contributor.author","Ott, German"],["dc.contributor.author","Porubsky, Stefan"],["dc.contributor.author","Preissler, Gerhard"],["dc.contributor.author","Popovic, Zoran V."],["dc.contributor.author","Sauer, Christian G."],["dc.contributor.author","Schölch, Sebastian"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Hielscher, Thomas"],["dc.contributor.author","Marx, Alexander"],["dc.date.accessioned","2021-10-01T09:58:20Z"],["dc.date.available","2021-10-01T09:58:20Z"],["dc.date.issued","2021"],["dc.date.updated","2022-09-04T10:01:51Z"],["dc.description.abstract","Thymomas are the most frequent adult mediastinal cancers. Their etiology is unknown and their pathogenesis poorly understood. Racial, ethnic and environmental factors influence tumorigenesis in many cancers, but their role in thymomas remains unclear to date. In this study that included pretreatment thymoma cases from India and Germany ( n = 37 and n = 77, respectively) we compared i) the prevalence of the thymoma-specific chromosome 7 c.74146970T > A mutation of the GTF2I gene in type A and AB thymomas; ii) epidemiological features; and iii) the frequency of myasthenia gravis (MG). Due to a known predominance of GTF2I mutation in A and AB histotypes, we included only a marginal number of type B thymomas as a control group in both cohorts. While the distribution of histological types between the cohorts was similar ( p = 0.1622), Indian patients were strikingly younger ( p < 0.0001; median age 50 vs. 65 years) and showed significantly lower tumour stage (Masaoka-Koga stage I) at primary diagnosis ( p = 0.0005) than the German patients. In patients with known MG status ( n = 17 in Indian and n = 25 in German cohort), a clear trend towards more frequent MG was observed in the Indian group ( p = 0.0504; 48 vs. 82%). The prevalence of the GTF2I mutation (analysed in n = 34 Indian and n = 77 German patients) was identical in the two cohorts. We conclude that racial-ethnic and environmental factors do not significantly influence the most common molecular feature of thymomas but may have an impact on the timing of clinical presentation."],["dc.identifier.doi","10.3389/pore.2021.1609858"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/90044"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-469"],["dc.relation.eissn","1532-2807"],["dc.rights","CC BY 4.0"],["dc.rights.uri","http://creativecommons.org/licenses/by/4.0/"],["dc.title","GTF2I Mutation in Thymomas: Independence From Racial-Ethnic Backgrounds. An Indian/German Comparative Study"],["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","381"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Histopathology"],["dc.bibliographiccitation.lastpage","396"],["dc.bibliographiccitation.volume","80"],["dc.contributor.affiliation","Richter, Annika; 1Institute of Pathology University Medical Centre Göttingen Göttingen Germany"],["dc.contributor.affiliation","Filmar, Simon; 1Institute of Pathology University Medical Centre Göttingen Göttingen Germany"],["dc.contributor.affiliation","Kircher, Stefan; 2Institute of Pathology University of Würzburg Würzburg Germany"],["dc.contributor.affiliation","Rosenwald, Andreas; 2Institute of Pathology University of Würzburg Würzburg Germany"],["dc.contributor.affiliation","Küffer, Stefan; 1Institute of Pathology University Medical Centre Göttingen Göttingen Germany"],["dc.contributor.affiliation","Nettersheim, Daniel; 3Department of Urology Urological Research Laboratory Translational UroOncology Medical Faculty and University Hospital Düsseldorf Heinrich‐Heine‐University Düsseldorf Germany"],["dc.contributor.affiliation","Oing, Christoph; 4Division of Pneumology Department of Oncology, Haematology and Bone Marrow Transplantation University Medical Centre Hamburg‐Eppendorf Hamburg Germany"],["dc.contributor.affiliation","Marx, Alexander; 6Institute of Pathology University Medical Centre Mannheim Mannheim Germany"],["dc.contributor.affiliation","Ströbel, Philipp; 1Institute of Pathology University Medical Centre Göttingen Göttingen Germany"],["dc.contributor.affiliation","Bremmer, Felix; 1Institute of Pathology University Medical Centre Göttingen Göttingen Germany"],["dc.contributor.author","Fichtner, Alexander"],["dc.contributor.author","Richter, Annika"],["dc.contributor.author","Filmar, Simon"],["dc.contributor.author","Kircher, Stefan"],["dc.contributor.author","Rosenwald, Andreas"],["dc.contributor.author","Küffer, Stefan"],["dc.contributor.author","Nettersheim, Daniel"],["dc.contributor.author","Oing, Christoph"],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Bremmer, Felix"],["dc.date.accessioned","2021-12-01T09:21:14Z"],["dc.date.available","2021-12-01T09:21:14Z"],["dc.date.issued","2021"],["dc.date.updated","2022-03-21T09:57:31Z"],["dc.description.abstract","Aims Primary mediastinal germ cell tumours (PMGCTs) are rare mediastinal neoplasms, and their diagnosis can be challenging, owing to small biopsy samples. The aim of this study was to develop a diagnostic algorithm using immunohistochemical staining, with a focus on novel markers, and molecular analysis of isochromosome 12p [i(12p)]. Methods and results Paraffin‐embedded tissues of 32 mediastinal tumours were analysed with immunohistochemical staining for sal‐like transcription factor 4 (SALL4), Lin‐28 homologue A (LIN28), octamer‐binding transcription factor 3/4 (OCT3/4), D2‐40, cluster of differentiation 117 (CD117), sex‐determining region Y‐box 17, sex‐determining region Y‐box 2 (SOX2), cluster of differentiation 30, the β‐subunit of human chorionic gonadotropin (β‐hCG), GATA‐binding protein 3 (GATA3), forkhead box protein A2 (FOXA2), glypican‐3 (GPC3), α‐fetoprotein (AFP), terminal deoxynucleotidyl transferase (TdT), nuclear protein of the testis (NUT), and pan‐cytokeratin. Quantitative real‐time polymerase chain reaction was performed to investigate the i(12p) status. Fifteen seminomas, seven teratomas, one yolk sac tumour, one choriocarcinoma and seven mixed PMGCTs were diagnosed. Each entity had different immunohistochemical staining patterns, which helped to distinguish them: OCT3/4, D2‐40, CD117 and TdT for seminoma; OCT3/4 and SOX2 for embryonal carcinoma; FOXA2, GPC3 and AFP for yolk sac tumour; and β‐hCG and GATA3 for choriocarcinoma. Mature teratomas stained positively for pan‐cytokeratin in epithelial components and focally for SALL4, SOX2, GATA3, D2‐40, and FOXA2. Furthermore, a NUT carcinoma mimicking a PMGCT was diagnosed, showing strong nuclear SOX2 staining and speckled nuclear NUT staining. i(12p) was detected in 24 of 27 PMGCTs (89%). Conclusion A diagnostic algorithm is of great importance for a reliable diagnosis of PMGCT in, usually small, tissue biopsy samples. Therefore, a combination of three to four antibodies to identify the correct histological subtype is usually necessary, in addition to morphological features. The i(12p) status serves as an additional option to indicate a germ cell origin in selected cases."],["dc.description.abstract","image"],["dc.description.sponsorship","Wilhelm Sander‐Stiftung http://dx.doi.org/10.13039/100008672"],["dc.identifier.doi","10.1111/his.14560"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94381"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation.eissn","1365-2559"],["dc.relation.issn","0309-0167"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made."],["dc.rights.uri","http://creativecommons.org/licenses/by-nc-nd/4.0/"],["dc.title","Primary mediastinal germ cell tumours: an immunohistochemical and molecular diagnostic approach"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","487"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Virchows Archiv"],["dc.bibliographiccitation.lastpage","500"],["dc.bibliographiccitation.volume","467"],["dc.contributor.author","den Bakker, Michael A."],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Mukai, Kiyoshi"],["dc.contributor.author","Stroebel, Philipp"],["dc.date.accessioned","2018-11-07T09:49:22Z"],["dc.date.available","2018-11-07T09:49:22Z"],["dc.date.issued","2015"],["dc.description.abstract","The mediastinum is an anatomically defined space in which organs and major blood vessels reside with surrounding soft tissue elements. The thymus is an important organ in the mediastinum, and many of the masses encountered in the mediastinum are related to this organ. Most neoplasms diagnosed in the mediastinum are epithelial tumours (thymomas and thymic carcinomas), lymphomas or germ cell tumours. In contrast, soft tissue tumours of the mediastinum are rare. In 1963, Pachter and Lattes systematically reviewed soft tissue pathology of the mediastinum, covering the hitherto described [2, 226, 227] In this review, based on the 2013 WHO classification of soft tissue tumours and the 2015 WHO classification of tumours of the lung, pleura, thymus and heart, we provide an updated overview of mesenchymal tumours that may be encountered in the mediastinum."],["dc.identifier.doi","10.1007/s00428-015-1830-8"],["dc.identifier.isi","000365516200002"],["dc.identifier.pmid","26358059"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12590"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35495"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1432-2307"],["dc.relation.issn","0945-6317"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Mesenchymal tumours of the mediastinum-part I"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","315"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Cancers"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Porubsky, Stefan"],["dc.contributor.author","Popovic, Zoran V."],["dc.contributor.author","Badve, Sunil"],["dc.contributor.author","Banz, Yara"],["dc.contributor.author","Berezowska, Sabina"],["dc.contributor.author","Borchert, Dietmar"],["dc.contributor.author","Brüggemann, Monika"],["dc.contributor.author","Gaiser, Timo"],["dc.contributor.author","Graeter, Thomas"],["dc.contributor.author","Hollaus, Peter"],["dc.contributor.author","Huettl, Katrin S."],["dc.contributor.author","Kotrova, Michaela"],["dc.contributor.author","Kreft, Andreas"],["dc.contributor.author","Kugler, Christian"],["dc.contributor.author","Lötscher, Fabian"],["dc.contributor.author","Möller, Burkhard"],["dc.contributor.author","Ott, German"],["dc.contributor.author","Preissler, Gerhard"],["dc.contributor.author","Roessner, Eric"],["dc.contributor.author","Rosenwald, Andreas"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Marx, Alexander"],["dc.date.accessioned","2021-04-14T08:29:47Z"],["dc.date.available","2021-04-14T08:29:47Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.3390/cancers13020315"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82986"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.publisher","MDPI"],["dc.relation.eissn","2072-6694"],["dc.rights","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Thymic Hyperplasia with Lymphoepithelial Sialadenitis (LESA)-Like Features: Strong Association with Lymphomas and Non-Myasthenic Autoimmune Diseases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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.firstpage","367"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Thoracic Oncology"],["dc.bibliographiccitation.lastpage","372"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Weis, Cleo-Aron"],["dc.contributor.author","Yao, Xiaopan"],["dc.contributor.author","Deng, Yanhong"],["dc.contributor.author","Detterbeck, Frank C."],["dc.contributor.author","Marino, Mirella"],["dc.contributor.author","Nicholson, Andrew G."],["dc.contributor.author","Huang, James"],["dc.contributor.author","Stroebel, Philipp"],["dc.contributor.author","Antonicelli, Alberto"],["dc.contributor.author","Marx, Alexander"],["dc.date.accessioned","2018-11-07T10:01:37Z"],["dc.date.available","2018-11-07T10:01:37Z"],["dc.date.issued","2015"],["dc.description.abstract","Introduction: The rarity of thymomas and lack of multi-institutional studies have hampered therapeutic progress for decades. To overcome this, the members of the International Thymic Malignancy Interest Group created a worldwide retrospective database. This database was analyzed regarding the demographic and geographic distribution of thymomas and the impact of different variables on survival and recurrence. Methods: This study analyzed 4221 thymomas diagnosed between 1983 and 2012 with World Health Organization histotype information from the International Thymic Malignancy Interest Group database. Associations to survival and recurrence were studied by univariate and multivariate analyses. Results: Type B2 thymoma is the most common (28%) and type A the least common (12%) histotypes. They are significantly more frequent in Europe and the United States than Asia. Type A and AB occur at significantly higher age than other thymomas (64 and 57 years, respectively). There are no differences in gender distribution. Stage is lower in type A (90% in stages I-II) and AB than B1 to B3 thymomas (38% of type B3 in stage III). In univariate analysis, recurrence is significantly less frequent among stage I/II tumors, in type A and AB (recurrence rates, 1-2%) than B1 to B3 thymomas (2-7%). Multivariate analysis reveals an impact of age, stage, and resection status on survival and recurrence, whereas for histology there is only a significant impact on recurrence. Conclusion: New findings are (1) geographic differences such as a lower incidence of type A and B2 thymoma in Asia; and (2) impact of stage and histology, the latter partially limited to early stage disease, on recurrence."],["dc.identifier.doi","10.1097/JTO.0000000000000393"],["dc.identifier.isi","000348829400024"],["dc.identifier.pmid","25616178"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13820"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38056"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1556-1380"],["dc.relation.issn","1556-0864"],["dc.rights","CC BY-NC-ND 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/3.0"],["dc.title","The Impact of Thymoma Histotype on Prognosis in a Worldwide Database"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["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.artnumber","972"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","BMC Cancer"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Haen, Sebastian P."],["dc.contributor.author","Stroebel, Philipp"],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Suesskind, Daniela"],["dc.contributor.author","Fend, Falko"],["dc.contributor.author","Reichmann, Ursula"],["dc.contributor.author","Kopp, Hans-Georg"],["dc.contributor.author","Kanz, Lothar"],["dc.contributor.author","Mayer, Frank"],["dc.date.accessioned","2019-07-09T11:41:58Z"],["dc.date.available","2019-07-09T11:41:58Z"],["dc.date.issued","2015"],["dc.description.abstract","Abstract Background Rare sites of metastases, atypical symptoms and paraneoplastic syndromes are often neglected or misinterpreted, especially when they represent early symptoms of an underlying malignant disease. Hence, an interdisciplinary approach to these patients is essential to avoid tumor progression and metastatic spread in order to provide curative treatment options to the patients. We here report the case of a young woman presenting with visual loss which led to diagnosis of a thymic carcinoma. Case presentation A 28-year old white woman presented with subacute loss of vision in the last trimester of her first pregnancy which was first interpreted as an exacerbation of a pre-existing dermatomyositis and treated with steroids. After failure of steroid therapy choroidal metastases from an undifferentiated thymic carcinoma were diagnosed. This also shed a new light on the dermatomyositis the patient had been suffering from for seven years possibly representing a paraneoplastic syndrome from the tumor. Despite aggressive chemotherapy, the patient died from progressive disease eight years after first onset of dermatomyositis and 14 months after initial diagnosis of the thymic carcinoma. Conclusions Choroidal metastases from a thymic carcinoma have never been reported before but should be included into the differential diagnosis of choroidal masses."],["dc.identifier.doi","10.1186/s12885-015-1968-4"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12651"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58562"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Choroidal metastases from thymic carcinoma during pregnancy: Case Report"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["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"]]