Küffer, Stefan

[["dc.bibliographiccitation.firstpage","2523"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Translational Lung Cancer Research"],["dc.bibliographiccitation.lastpage","2538"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Yao, Sha"],["dc.contributor.author","Peng, Luogen"],["dc.contributor.author","Elakad, Omar"],["dc.contributor.author","Küffer, Stefan"],["dc.contributor.author","Hinterthaner, Marc"],["dc.contributor.author","Danner, Bernhard C."],["dc.contributor.author","Hammerstein-Equord, Alexander von"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.date.accessioned","2021-08-12T07:45:40Z"],["dc.date.available","2021-08-12T07:45:40Z"],["dc.date.issued","2021"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.21037/tlcr-20-1039"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/88522"],["dc.notes.intern","DOI Import GROB-448"],["dc.relation.eissn","2226-4477"],["dc.relation.issn","2218-6751"],["dc.relation.orgunit","Institut für Pathologie"],["dc.rights","CC BY-NC-ND 4.0"],["dc.title","One carbon metabolism in human lung cancer"],["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","593"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Histopathology"],["dc.bibliographiccitation.lastpage","606"],["dc.bibliographiccitation.volume","78"],["dc.contributor.author","Fichtner, Alexander"],["dc.contributor.author","Richter, Annika"],["dc.contributor.author","Filmar, Simon"],["dc.contributor.author","Gaisa, Nadine T"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Reis, Henning"],["dc.contributor.author","Nettersheim, Daniel"],["dc.contributor.author","Oing, Christoph"],["dc.contributor.author","Gayer, Fabian A"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Küffer, Stefan"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Kaulfuß, Silke"],["dc.contributor.author","Bremmer, Felix"],["dc.date.accessioned","2021-04-14T08:23:39Z"],["dc.date.available","2021-04-14T08:23:39Z"],["dc.date.issued","2020"],["dc.description.abstract","Aims Malignant germ cell tumours (GCTs) of the testis are rare neoplasms, but the most common solid malignancies in young men. World Health Organization guidelines divide GCTs into five types, for which numerous immunohistochemical markers allow exact histological subtyping in the majority of cases. In contrast, a germ cell origin is often hard to prove in metastatic GCTs that have developed so‐called somatic malignant transformation. A high percentage, up to 89%, of GCTs are characterised by the appearance of isochromosome 12p [i(12p)]. Fluorescence in‐situ hybridisation has been the most common diagnostic method for the detection of i(12p) so far, but has the disadvantages of being time‐consuming, demanding, and not being a stand‐alone method. The aim of the present study was to establish a quantitative real‐time polymerase chain reaction assay as an independent method for detecting i(12p) and regional amplifications of the short arm of chromosome 12 by using DNA extracted from formalin‐fixed paraffin‐embedded tissue. Methods and results A cut‐off value to distinguish between the presence and absence of i(12p) was established in a control set consisting of 36 tumour‐free samples. In a training set of 149 GCT samples, i(12p) was detectable in 133 tumours (89%), but not in 16 tumours (11%). In a test set containing 27 primary and metastatic GCTs, all 16 tumours with metastatic spread and/or somatic malignant transformation were successfully identified by the detection of i(12p). Conclusion In summary, the qPCR assay presented here can help to identify, further characterise and assign a large proportion of histologically inconclusive malignancies to a GCT origin."],["dc.description.sponsorship","Wilhelm Sander‐Stiftung http://dx.doi.org/10.13039/100008672"],["dc.identifier.doi","10.1111/his.14258"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81003"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["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 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited."],["dc.title","The detection of isochromosome i(12p) in malignant germ cell tumours and tumours with somatic malignant transformation by the use of quantitative real‐time polymerase chain reaction"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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","33"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The Journal of Pathology: Clinical Research"],["dc.bibliographiccitation.lastpage","47"],["dc.bibliographiccitation.volume","8"],["dc.contributor.affiliation","Fichtner, Alexander; 1\r\nInstitute of Pathology\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Joost, Jasmin; 1\r\nInstitute of Pathology\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Brockmeyer, Philipp; 2\r\nDepartment of Oral and Maxillofacial Surgery\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Kauffmann, Philipp; 2\r\nDepartment of Oral and Maxillofacial Surgery\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Schliephake, Henning; 2\r\nDepartment of Oral and Maxillofacial Surgery\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Hammerstein‐Equord, Alexander; 3\r\nDepartment of Thoracic and Cardiovascular Surgery\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Kueffer, Stefan; 1\r\nInstitute of Pathology\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Urlaub, Henning; 4\r\nBioanalytical Mass Spectrometry Group\r\nMax Planck Institute for Biophysical Chemistry\r\nGöttingen Germany"],["dc.contributor.affiliation","Oellerich, Thomas; 6\r\nDepartment of Medicine II, Haematology/Oncology\r\nGoethe University\r\nFrankfurt Germany"],["dc.contributor.affiliation","Ströbel, Philipp; 1\r\nInstitute of Pathology\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Bohnenberger, Hanibal; 1\r\nInstitute of Pathology\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Bremmer, Felix; 1\r\nInstitute of Pathology\r\nUniversity Medical Centre Göttingen\r\nGöttingen Germany"],["dc.contributor.author","Richter, Annika"],["dc.contributor.author","Fichtner, Alexander"],["dc.contributor.author","Joost, Jasmin"],["dc.contributor.author","Brockmeyer, Philipp"],["dc.contributor.author","Kauffmann, Philipp"],["dc.contributor.author","Schliephake, Henning"],["dc.contributor.author","Hammerstein‐Equord, Alexander"],["dc.contributor.author","Kueffer, Stefan"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.date.accessioned","2021-12-01T09:23:20Z"],["dc.date.available","2021-12-01T09:23:20Z"],["dc.date.issued","2021"],["dc.date.updated","2022-03-20T23:05:20Z"],["dc.description.abstract","Abstract The differentiation between a pulmonary metastasis and a newly developed squamous cell carcinoma of the lung in patients with prior head and neck squamous cell carcinoma (HNSCC) is difficult due to a lack of biomarkers but is crucially important for the prognosis and therapy of the affected patient. By using high‐resolution mass spectrometry in combination with stable isotope labelling by amino acids in cell culture, we identified 379 proteins that are differentially expressed in squamous cell carcinomas of the lung and the head and neck. Of those, CAV1, CAV2, LGALS1, LGALS7, CK19, and UGDH were tested by immunohistochemistry on 194 tissue samples (98 lung and 96 HNSCCs). The combination of CAV1 and LGALS7 was able to distinguish the origin of the squamous cell carcinoma with high accuracy (area under the curve 0.876). This biomarker panel was tested on a cohort of 12 clinically classified lung tumours of unknown origin after HNSCC. Nine of those tumours were immunohistochemically classifiable."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.1002/cjp2.244"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94624"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation.eissn","2056-4538"],["dc.rights","CC BY-NC-ND 4.0"],["dc.title","Quantitative proteomics identifies biomarkers to distinguish pulmonary from head and neck squamous cell carcinomas by immunohistochemistry"],["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","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.issue","7"],["dc.bibliographiccitation.journal","Metabolites"],["dc.bibliographiccitation.volume","12"],["dc.contributor.affiliation","Li, Yuchan; 1Institute of Pathology, University Medical Center, 37075 Göttingen, Germany; yuchan.li@stud.uni-goettingen.de (Y.L.); omarakkad14@gmail.com (O.E.); yaosha2016@gmail.com (S.Y.); carmelo.ferrai@med.uni-goettingen.de (C.F.); philipp.stroebel@med.uni-goettingen.de (P.S.)"],["dc.contributor.affiliation","Elakad, Omar; 1Institute of Pathology, University Medical Center, 37075 Göttingen, Germany; yuchan.li@stud.uni-goettingen.de (Y.L.); omarakkad14@gmail.com (O.E.); yaosha2016@gmail.com (S.Y.); carmelo.ferrai@med.uni-goettingen.de (C.F.); philipp.stroebel@med.uni-goettingen.de (P.S.)"],["dc.contributor.affiliation","Yao, Sha; 1Institute of Pathology, University Medical Center, 37075 Göttingen, Germany; yuchan.li@stud.uni-goettingen.de (Y.L.); omarakkad14@gmail.com (O.E.); yaosha2016@gmail.com (S.Y.); carmelo.ferrai@med.uni-goettingen.de (C.F.); philipp.stroebel@med.uni-goettingen.de (P.S.)"],["dc.contributor.affiliation","von Hammerstein-Equord, Alexander; 4Department of Thoracic and Cardiovascular Surgery, University Medical Center, 37075 Göttingen, Germany; alexander.hammerstein@med.uni-goettingen.de (A.v.H.-E.); marc.hinterthaner@med.uni-goettingen.de (M.H.); bernd.danner@med.uni-goettingen.de (B.C.D.)"],["dc.contributor.affiliation","Hinterthaner, Marc; 4Department of Thoracic and Cardiovascular Surgery, University Medical Center, 37075 Göttingen, Germany; alexander.hammerstein@med.uni-goettingen.de (A.v.H.-E.); marc.hinterthaner@med.uni-goettingen.de (M.H.); bernd.danner@med.uni-goettingen.de (B.C.D.)"],["dc.contributor.affiliation","Danner, Bernhard C.; 4Department of Thoracic and Cardiovascular Surgery, University Medical Center, 37075 Göttingen, Germany; alexander.hammerstein@med.uni-goettingen.de (A.v.H.-E.); marc.hinterthaner@med.uni-goettingen.de (M.H.); bernd.danner@med.uni-goettingen.de (B.C.D.)"],["dc.contributor.affiliation","Ferrai, Carmelo; 1Institute of Pathology, University Medical Center, 37075 Göttingen, Germany; yuchan.li@stud.uni-goettingen.de (Y.L.); omarakkad14@gmail.com (O.E.); yaosha2016@gmail.com (S.Y.); carmelo.ferrai@med.uni-goettingen.de (C.F.); philipp.stroebel@med.uni-goettingen.de (P.S.)"],["dc.contributor.affiliation","Ströbel, Philipp; 1Institute of Pathology, University Medical Center, 37075 Göttingen, Germany; yuchan.li@stud.uni-goettingen.de (Y.L.); omarakkad14@gmail.com (O.E.); yaosha2016@gmail.com (S.Y.); carmelo.ferrai@med.uni-goettingen.de (C.F.); philipp.stroebel@med.uni-goettingen.de (P.S.)"],["dc.contributor.affiliation","Küffer, Stefan; 1Institute of Pathology, University Medical Center, 37075 Göttingen, Germany; yuchan.li@stud.uni-goettingen.de (Y.L.); omarakkad14@gmail.com (O.E.); yaosha2016@gmail.com (S.Y.); carmelo.ferrai@med.uni-goettingen.de (C.F.); philipp.stroebel@med.uni-goettingen.de (P.S.)"],["dc.contributor.affiliation","Bohnenberger, Hanibal; 1Institute of Pathology, University Medical Center, 37075 Göttingen, Germany; yuchan.li@stud.uni-goettingen.de (Y.L.); omarakkad14@gmail.com (O.E.); yaosha2016@gmail.com (S.Y.); carmelo.ferrai@med.uni-goettingen.de (C.F.); philipp.stroebel@med.uni-goettingen.de (P.S.)"],["dc.contributor.author","Li, Yuchan"],["dc.contributor.author","Elakad, Omar"],["dc.contributor.author","Yao, Sha"],["dc.contributor.author","von Hammerstein-Equord, Alexander"],["dc.contributor.author","Hinterthaner, Marc"],["dc.contributor.author","Danner, Bernhard C."],["dc.contributor.author","Ferrai, Carmelo"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Küffer, Stefan"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.date.accessioned","2022-08-04T08:28:51Z"],["dc.date.available","2022-08-04T08:28:51Z"],["dc.date.issued","2022-07-15"],["dc.date.updated","2022-08-03T15:44:46Z"],["dc.description.abstract","Activating KRAS mutations occur in about 30% of pulmonary adenocarcinoma (AC) cases and the discovery of specific inhibitors of G12C-mutated KRAS has considerably improved the prognosis for a subgroup of about 14% of non-small cell lung cancer (NSCLC) patients. However, even in patients with a KRAS G12C mutation, the overall response rate only reaches about 40% and mutations other than G12C still cannot be targeted. Despite the fact that one-carbon metabolism (1CM) and epigenetic regulation are known to be dysregulated by aberrant KRAS activity, we still lack evidence that co-treatment with drugs that regulate these factors might ameliorate response rates and patient prognosis. In this study, we show a direct dependency of Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) and Enhancer of Zeste Homolog 2 (EZH2) expression on mutationally activated KRAS and their prognostic relevance in KRAS-mutated AC. We show that aberrant KRAS activity generates a vulnerability of AC cancer cell lines to both MTHFD2 and EZH2 inhibitors. Importantly, co-inhibition of both factors was synergistically effective and comparable to KRASG12C inhibition alone, paving the way for their use in a therapeutic approach for NSCLC cancer patients."],["dc.description.sponsorship","Deutsche Krebshilfe Foundation"],["dc.description.sponsorship","University Medical Center Göttingen"],["dc.description.sponsorship","Else-Kröner-Fresenius-Foundation"],["dc.description.sponsorship","Chinese Scholarship Counsil"],["dc.description.sponsorship","DFG"],["dc.identifier.doi","10.3390/metabo12070652"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112626"],["dc.language.iso","en"],["dc.relation.eissn","2218-1989"],["dc.rights","CC BY 4.0"],["dc.title","Regulation and Therapeutic Targeting of MTHFD2 and EZH2 in KRAS-Mutated Human Pulmonary Adenocarcinoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Disease Markers"],["dc.bibliographiccitation.lastpage","14"],["dc.bibliographiccitation.volume","2019"],["dc.contributor.author","Bremmer, Felix"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Küffer, Stefan"],["dc.contributor.author","Oellerich, Thomas"],["dc.contributor.author","Serve, Hubert"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Strauß, Arne"],["dc.contributor.author","Maatoug, Yasmine"],["dc.contributor.author","Behnes, Carl Ludwig"],["dc.contributor.author","Oing, Christoph"],["dc.contributor.author","Radzun, Heinz Joachim"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Balabanov, Stefan"],["dc.contributor.author","Honecker, Friedemann"],["dc.date.accessioned","2019-09-24T07:40:13Z"],["dc.date.available","2019-09-24T07:40:13Z"],["dc.date.issued","2019"],["dc.description.abstract","Malignant germ cell tumors (GCT) are the most common malignant tumors in young men between 18 and 40 years. The correct identification of histological subtypes, in difficult cases supported by immunohistochemistry, is essential for therapeutic management. Furthermore, biomarkers may help to understand pathophysiological processes in these tumor types. Two GCT cell lines, TCam-2 with seminoma-like characteristics, and NTERA-2, an embryonal carcinoma-like cell line, were compared by a quantitative proteomic approach using high-resolution mass spectrometry (MS) in combination with stable isotope labelling by amino acid in cell culture (SILAC). We were able to identify 4856 proteins and quantify the expression of 3936. 347 were significantly differentially expressed between the two cell lines. For further validation, CD81, CBX-3, PHF6, and ENSA were analyzed by western blot analysis. The results confirmed the MS results. Immunohistochemical analysis on 59 formalin-fixed and paraffin-embedded (FFPE) normal and GCT tissue samples (normal testis, GCNIS, seminomas, and embryonal carcinomas) of these proteins demonstrated the ability to distinguish different GCT subtypes, especially seminomas and embryonal carcinomas. In addition, siRNA-mediated knockdown of these proteins resulted in an antiproliferative effect in TCam-2, NTERA-2, and an additional embryonal carcinoma-like cell line, NCCIT. In summary, this study represents a proteomic resource for the discrimination of malignant germ cell tumor subtypes and the observed antiproliferative effect after knockdown of selected proteins paves the way for the identification of new potential drug targets."],["dc.identifier.doi","10.1155/2019/8298524"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16378"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62439"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","0278-0240"],["dc.relation.issn","1875-8630"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Proteomic Comparison of Malignant Human Germ Cell Tumor Cell Lines"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e154475"],["dc.bibliographiccitation.issue","16"],["dc.bibliographiccitation.journal","JCI Insight"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Krebs, Niklas"],["dc.contributor.author","Klein, Lukas"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Espinet, Elisa"],["dc.contributor.author","Maurer, Hans Carlo"],["dc.contributor.author","Tu, Mengyu"],["dc.contributor.author","Penz, Frederike"],["dc.contributor.author","Küffer, Stefan"],["dc.contributor.author","Xu, Xingbo"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Singh, Shiv K."],["dc.date.accessioned","2022-09-01T09:50:53Z"],["dc.date.available","2022-09-01T09:50:53Z"],["dc.date.issued","2022"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.1172/jci.insight.154475"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113823"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-597"],["dc.relation.eissn","2379-3708"],["dc.title","Axon guidance receptor ROBO3 modulates subtype identity and prognosis via AXL-associated inflammatory network in pancreatic cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1472"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Journal of Thoracic Oncology"],["dc.bibliographiccitation.lastpage","1483"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Dinter, Helen"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Beck, Julia"],["dc.contributor.author","Bornemann-Kolatzki, Kirsten"],["dc.contributor.author","Schütz, Ekkehard"],["dc.contributor.author","Küffer, Stefan"],["dc.contributor.author","Klein, Lukas"],["dc.contributor.author","Franks, Teri J."],["dc.contributor.author","Roden, Anja"],["dc.contributor.author","Emmert, Alexander"],["dc.contributor.author","Hinterthaner, Marc"],["dc.contributor.author","Marino, Mirella"],["dc.contributor.author","Brcic, Luka"],["dc.contributor.author","Popper, Helmut"],["dc.contributor.author","Weis, Cleo-Aron"],["dc.contributor.author","Pelosi, Giuseppe"],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Ströbel, Philipp"],["dc.date.accessioned","2020-12-10T15:20:08Z"],["dc.date.available","2020-12-10T15:20:08Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/j.jtho.2019.04.015"],["dc.identifier.issn","1556-0864"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16734"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72564"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Molecular Classification of Neuroendocrine Tumors of the Thymus"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4762"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Cancers"],["dc.bibliographiccitation.volume","14"],["dc.contributor.affiliation","Küffer, Stefan; 1Institute of Pathology, University Medical Center Göttingen, University of Göttingen, 37075 Göttingen, Germany"],["dc.contributor.affiliation","Grabowski, Jessica; 1Institute of Pathology, University Medical Center Göttingen, University of Göttingen, 37075 Göttingen, Germany"],["dc.contributor.affiliation","Okada, Satoru; 1Institute of Pathology, University Medical Center Göttingen, University of Göttingen, 37075 Göttingen, Germany"],["dc.contributor.affiliation","Sojka, Nikolai; 1Institute of Pathology, University Medical Center Göttingen, University of Göttingen, 37075 Göttingen, Germany"],["dc.contributor.affiliation","Welter, Stefan; 3Thoracic Surgery Department, Lung Clinic Hemer, 58675 Hemer, Germany"],["dc.contributor.affiliation","von Hammerstein-Equord, Alexander; 4Department of Thoracic and Cardiovascular Surgery, University Medical Center, 37075 Göttingen, Germany"],["dc.contributor.affiliation","Hinterthaner, Marc; 4Department of Thoracic and Cardiovascular Surgery, University Medical Center, 37075 Göttingen, Germany"],["dc.contributor.affiliation","Cordes, Lucia; 3Thoracic Surgery Department, Lung Clinic Hemer, 58675 Hemer, Germany"],["dc.contributor.affiliation","von Hahn, Xenia; 1Institute of Pathology, University Medical Center Göttingen, University of Göttingen, 37075 Göttingen, Germany"],["dc.contributor.affiliation","Müller, Denise; 1Institute of Pathology, University Medical Center Göttingen, University of Göttingen, 37075 Göttingen, Germany"],["dc.contributor.affiliation","Sauer, Christian; 5Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, Germany"],["dc.contributor.affiliation","Bohnenberger, Hanibal; 1Institute of Pathology, University Medical Center Göttingen, University of Göttingen, 37075 Göttingen, Germany"],["dc.contributor.affiliation","Marx, Alexander; 5Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, Germany"],["dc.contributor.affiliation","Ströbel, Philipp; 1Institute of Pathology, University Medical Center Göttingen, University of Göttingen, 37075 Göttingen, Germany"],["dc.contributor.author","Küffer, Stefan"],["dc.contributor.author","Grabowski, Jessica"],["dc.contributor.author","Okada, Satoru"],["dc.contributor.author","Sojka, Nikolai"],["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","von Hahn, Xenia"],["dc.contributor.author","Müller, Denise"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Sauer, Christian"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Marx, Alexander"],["dc.contributor.editor","Wong, David"],["dc.date.accessioned","2022-11-01T10:17:23Z"],["dc.date.available","2022-11-01T10:17:23Z"],["dc.date.issued","2022"],["dc.date.updated","2022-11-11T13:13:11Z"],["dc.description.abstract","Background: After initially responding to empiric radio-chemotherapy, most advanced thymomas (TH) and thymic carcinomas (TC) become refractory and require second-line therapy. The multi-target receptor tyrosine kinase (RTK) inhibitor, sunitinib, is one of the few options, especially in patients with thymic carcinomas, and has resulted in partial remissions and prolonged overall survival. However, sunitinib shows variable activity in thymomas, and not all patients benefit equally. A better understanding of its mode of action and the definition of predictive biomarkers would help select patients who profit most. Methods: Six cell lines were treated with sunitinib in vitro. Cell viability was measured by MTS assay and used to define in vitro responders and non-responders. A quantitative real-time assay simultaneously measuring the phosphorylation of 144 tyrosine kinase substrates was used to correlate cell viability with alterations of the phospho-kinome, calculate a sunitinib response index (SRI), and impute upstream tyrosine kinases. Sunitinib was added to protein lysates of 29 malignant TH and TC. Lysates were analyzed with the same phosphorylation assay. The SRI tentatively classified cases into potential clinical responders and non-responders. In addition, the activation patterns of 44 RTKs were studied by phospho-RTK arrays in 37 TH and TC. Results: SRI application separated thymic epithelial tumors (TET) in potential sunitinib responders and resistant cases. Upstream kinase prediction identified multiple RTKs potentially involved in sunitinib response, many of which were subsequently shown to be differentially overexpressed in TH and TC. Among these, TYRO3/Dtk stood out since it was exclusively present in metastatic TH. The function of TYRO3 as a mediator of sunitinib resistance was experimentally validated in vitro. Conclusions: Using indirect and direct phosphoproteomic analyses to predict sunitinib response in malignant TET, we have shown that TH and TC express multiple important sunitinib target RTKs. Among these, TYRO3 was identified as a potent mediator of sunitinib resistance activity, specifically in metastatic TH. TYRO3 may thus be both a novel biomarker of sunitinib resistance and a potential therapeutic target in advanced thymomas and thymic carcinomas."],["dc.identifier.doi","10.3390/cancers14194762"],["dc.identifier.pii","cancers14194762"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/116799"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-605"],["dc.publisher","MDPI"],["dc.relation.eissn","2072-6694"],["dc.rights","Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)."],["dc.title","Phosphoproteomic Analysis Identifies TYRO3 as a Mediator of Sunitinib Resistance in Metastatic Thymomas"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]