König, Alexander Otto

[["dc.bibliographiccitation.firstpage","S29"],["dc.bibliographiccitation.journal","Translational Cancer Research"],["dc.bibliographiccitation.lastpage","S30"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Koenig, Alexander O."],["dc.date.accessioned","2018-11-07T10:27:48Z"],["dc.date.available","2018-11-07T10:27:48Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.21037/tcr.2017.02.32"],["dc.identifier.isi","000397306100010"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43301"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Ame Publ Co"],["dc.relation.issn","2219-6803"],["dc.relation.issn","2218-676X"],["dc.title","Interaction of tumor and stromal cells in pancreatic cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.subtype","letter_note"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2828"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Cancers"],["dc.bibliographiccitation.volume","14"],["dc.contributor.affiliation","Bremer, Sebastian C. B.; 1Clinic for Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; alexander.koenig@med.uni-goettingen.de (A.O.K.); ahmad.amanzada@med.uni-goettingen.de (A.A.); volker.ellenrieder@med.uni-goettingen.de (V.E.)"],["dc.contributor.affiliation","Bittner, Gabi; 2Institute of Pathology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; bittnergabi@outlook.de (G.B.); omar.elakad@med.uni-goettingen.de (O.E.); dinterhelen@gmail.com (H.D.); philipp.stroebel@med.uni-goettingen.de (P.S.); hanibal.bohnenberger@med.uni-goettingen.de (H.B.)"],["dc.contributor.affiliation","Elakad, Omar; 2Institute of Pathology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; bittnergabi@outlook.de (G.B.); omar.elakad@med.uni-goettingen.de (O.E.); dinterhelen@gmail.com (H.D.); philipp.stroebel@med.uni-goettingen.de (P.S.); hanibal.bohnenberger@med.uni-goettingen.de (H.B.)"],["dc.contributor.affiliation","Dinter, Helen; 2Institute of Pathology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; bittnergabi@outlook.de (G.B.); omar.elakad@med.uni-goettingen.de (O.E.); dinterhelen@gmail.com (H.D.); philipp.stroebel@med.uni-goettingen.de (P.S.); hanibal.bohnenberger@med.uni-goettingen.de (H.B.)"],["dc.contributor.affiliation","Gaedcke, Jochen; 3Clinic for General, Visceral and Pediatric Surgery, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; jochen.gaedcke@med.uni-goettingen.de"],["dc.contributor.affiliation","König, Alexander O.; 1Clinic for Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; alexander.koenig@med.uni-goettingen.de (A.O.K.); ahmad.amanzada@med.uni-goettingen.de (A.A.); volker.ellenrieder@med.uni-goettingen.de (V.E.)"],["dc.contributor.affiliation","Amanzada, Ahmad; 1Clinic for Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; alexander.koenig@med.uni-goettingen.de (A.O.K.); ahmad.amanzada@med.uni-goettingen.de (A.A.); volker.ellenrieder@med.uni-goettingen.de (V.E.)"],["dc.contributor.affiliation","Ellenrieder, Volker; 1Clinic for Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; alexander.koenig@med.uni-goettingen.de (A.O.K.); ahmad.amanzada@med.uni-goettingen.de (A.A.); volker.ellenrieder@med.uni-goettingen.de (V.E.)"],["dc.contributor.affiliation","Freiherr von Hammerstein-Equord, Alexander; 4Clinic for Cardiac, Thoracic and Vascular Surgery, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; alexander.hammerstein@med.uni-goettingen.de"],["dc.contributor.affiliation","Ströbel, Philipp; 2Institute of Pathology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; bittnergabi@outlook.de (G.B.); omar.elakad@med.uni-goettingen.de (O.E.); dinterhelen@gmail.com (H.D.); philipp.stroebel@med.uni-goettingen.de (P.S.); hanibal.bohnenberger@med.uni-goettingen.de (H.B.)"],["dc.contributor.affiliation","Bohnenberger, Hanibal; 2Institute of Pathology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; bittnergabi@outlook.de (G.B.); omar.elakad@med.uni-goettingen.de (O.E.); dinterhelen@gmail.com (H.D.); philipp.stroebel@med.uni-goettingen.de (P.S.); hanibal.bohnenberger@med.uni-goettingen.de (H.B.)"],["dc.contributor.author","Bremer, Sebastian C. B."],["dc.contributor.author","Bittner, Gabi"],["dc.contributor.author","Elakad, Omar"],["dc.contributor.author","Dinter, Helen"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","König, Alexander O."],["dc.contributor.author","Amanzada, Ahmad"],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Freiherr von Hammerstein-Equord, Alexander"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.date.accessioned","2022-07-01T07:35:31Z"],["dc.date.available","2022-07-01T07:35:31Z"],["dc.date.issued","2022"],["dc.date.updated","2022-07-08T10:03:36Z"],["dc.description.abstract","Tumor grading is a robust prognostic predictor in patients with neuroendocrine neoplasms (NEN) and guides therapy, especially in tumors with high proliferation. NEN can be separated into well-differentiated and poorly differentiated types. The more aggressive NEN have been further separated into neuroendocrine tumors (NET G3) with a better prognosis and neuroendocrine carcinomas (NEC) with a worse prognosis. Despite this distinction’s tremendous clinical and therapeutic relevance, optimal diagnostic biomarkers are still lacking. In this study, we analyzed the protein expression and prognostic impact of Enhancer of Zeste Homolog 2 (EZH2) by immunohistochemistry in 219 tissue samples of gastroenteropancreatic (GEP-NEN) and pulmonary NEN (P-NEN). EZH2 was almost exclusively expressed in NEN with a proliferation rate above 20% (G3), while all low-grade tumors were nearly negative. Among high-grade NEN, 65% showed high and 35% low expression of EZH2. In this group, the high expression of EZH2 was significantly associated with poor overall survival and NEC histology. Interestingly, EZH2 seems to act independently of Polycomb Repressive Complex 2 (PRC2) in NEN. In conclusion, we propose EZH2 as a robust biomarker for distinguishing between NET G3 and NEC among gastroenteropancreatic and pulmonary NEN."],["dc.description.sponsorship","Deutsche Krebshilfe"],["dc.description.sponsorship","University Medical Center Göttingen"],["dc.description.sponsorship","Else-Kröner-Fresenius-Stiftung"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.3390/cancers14122828"],["dc.identifier.pii","cancers14122828"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112190"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112412"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-581"],["dc.relation.eissn","2072-6694"],["dc.rights","CC BY 4.0"],["dc.title","Enhancer of Zeste Homolog 2 (EZH2) Is a Marker of High-Grade Neuroendocrine Neoplasia in Gastroenteropancreatic and Pulmonary Tract and Predicts Poor Prognosis"],["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","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Azizian, Azadeh"],["dc.contributor.author","Rühlmann, Felix"],["dc.contributor.author","Krause, Tanja"],["dc.contributor.author","Bernhardt, Markus"],["dc.contributor.author","Jo, Peter"],["dc.contributor.author","König, Alexander"],["dc.contributor.author","Kleiß, Mathias"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Ghadimi, Michael"],["dc.contributor.author","Gaedcke, Jochen"],["dc.date.accessioned","2021-04-14T08:27:35Z"],["dc.date.available","2021-04-14T08:27:35Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1038/s41598-020-57930-x"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82341"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","2045-2322"],["dc.title","CA19-9 for detecting recurrence of pancreatic cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1301"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Cancers"],["dc.bibliographiccitation.volume","14"],["dc.contributor.affiliation","Flebbe, Hannah; 1Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, Germany; hannah.flebbe@med.uni-goettingen.de (H.F.); melanie.spitzner@med.uni-goettingen.de (M.S.); pmarquet@tabea-krankenhaus.de (P.E.M.); jochen.gaedcke@med.uni-goettingen.de (J.G.); mghadim@uni-goettingen.de (B.M.G.); guenter.schneider@med.uni-goettingen.de (G.S.)"],["dc.contributor.affiliation","Spitzner, Melanie; 1Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, Germany; hannah.flebbe@med.uni-goettingen.de (H.F.); melanie.spitzner@med.uni-goettingen.de (M.S.); pmarquet@tabea-krankenhaus.de (P.E.M.); jochen.gaedcke@med.uni-goettingen.de (J.G.); mghadim@uni-goettingen.de (B.M.G.); guenter.schneider@med.uni-goettingen.de (G.S.)"],["dc.contributor.affiliation","Marquet, Philipp Enno; 1Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, Germany; hannah.flebbe@med.uni-goettingen.de (H.F.); melanie.spitzner@med.uni-goettingen.de (M.S.); pmarquet@tabea-krankenhaus.de (P.E.M.); jochen.gaedcke@med.uni-goettingen.de (J.G.); mghadim@uni-goettingen.de (B.M.G.); guenter.schneider@med.uni-goettingen.de (G.S.)"],["dc.contributor.affiliation","Gaedcke, Jochen; 1Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, Germany; hannah.flebbe@med.uni-goettingen.de (H.F.); melanie.spitzner@med.uni-goettingen.de (M.S.); pmarquet@tabea-krankenhaus.de (P.E.M.); jochen.gaedcke@med.uni-goettingen.de (J.G.); mghadim@uni-goettingen.de (B.M.G.); guenter.schneider@med.uni-goettingen.de (G.S.)"],["dc.contributor.affiliation","Ghadimi, B. Michael; 1Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, Germany; hannah.flebbe@med.uni-goettingen.de (H.F.); melanie.spitzner@med.uni-goettingen.de (M.S.); pmarquet@tabea-krankenhaus.de (P.E.M.); jochen.gaedcke@med.uni-goettingen.de (J.G.); mghadim@uni-goettingen.de (B.M.G.); guenter.schneider@med.uni-goettingen.de (G.S.)"],["dc.contributor.affiliation","Rieken, Stefan; 3Department of Radiotherapy and Radiooncology, University Medical Center Goettingen, 37075 Goettingen, Germany; stefan.rieken@med.uni-goettingen.de"],["dc.contributor.affiliation","Schneider, Günter; 1Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, Germany; hannah.flebbe@med.uni-goettingen.de (H.F.); melanie.spitzner@med.uni-goettingen.de (M.S.); pmarquet@tabea-krankenhaus.de (P.E.M.); jochen.gaedcke@med.uni-goettingen.de (J.G.); mghadim@uni-goettingen.de (B.M.G.); guenter.schneider@med.uni-goettingen.de (G.S.)"],["dc.contributor.affiliation","Koenig, Alexander O.; 4Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, 37075 Goettingen, Germany; alexander.koenig@med.uni-goettingen.de"],["dc.contributor.affiliation","Grade, Marian; 1Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, Germany; hannah.flebbe@med.uni-goettingen.de (H.F.); melanie.spitzner@med.uni-goettingen.de (M.S.); pmarquet@tabea-krankenhaus.de (P.E.M.); jochen.gaedcke@med.uni-goettingen.de (J.G.); mghadim@uni-goettingen.de (B.M.G.); guenter.schneider@med.uni-goettingen.de (G.S.)"],["dc.contributor.author","Flebbe, Hannah"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Marquet, Philipp Enno"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Ghadimi, B. Michael"],["dc.contributor.author","Rieken, Stefan"],["dc.contributor.author","Schneider, Günter"],["dc.contributor.author","Koenig, Alexander O."],["dc.contributor.author","Grade, Marian"],["dc.date.accessioned","2022-04-01T10:00:34Z"],["dc.date.available","2022-04-01T10:00:34Z"],["dc.date.issued","2022"],["dc.date.updated","2022-04-08T08:31:13Z"],["dc.description.abstract","The debate is ongoing regarding the potential role of preoperative chemoradiotherapy (CRT) for patients with pancreatic ductal adenocarcinoma (PDAC), and whether it should be reserved for borderline resectable or unresectable tumors. However, treatment response is heterogeneous, implicating the need to unveil and overcome the underlying mechanisms of resistance. Activation of the transcription factor STAT3 was recently linked to CRT resistance in other gastrointestinal cancers such as rectal and esophageal cancers, but its role in PDAC needs to be clarified. Protein expression and phosphorylation of STAT3 was determined in PDAC cell lines and connected to transcriptional activity measured by dual-luciferase reporter gene assays. Inhibition of STAT3 signaling was achieved by RNAi or the small-molecule inhibitor napabucasin. We observed a positive correlation between STAT3 signaling activity and CRT resistance. Importantly, genetical and pharmacological perturbation of the IL-6/STAT3 pathway resulted in CRT sensitization specifically in those cell lines, in which STAT3 activity was augmented by IL-6. In conclusion, our data underscore the general importance of IL-6/STAT3 signaling for CRT resistance and suggest that pathway inhibition may represents a putative treatment strategy in order to increase the fraction of patients with PDAC who are candidates for surgical approaches."],["dc.identifier.doi","10.3390/cancers14051301"],["dc.identifier.pii","cancers14051301"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105459"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["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","Targeting STAT3 Signaling Facilitates Responsiveness of Pancreatic Cancer Cells to Chemoradiotherapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1507"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Gastroenterology"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","152"],["dc.contributor.author","Chen, Nai-Ming"],["dc.contributor.author","Neeße, Albrecht"],["dc.contributor.author","Dyck, Moritz Lino"],["dc.contributor.author","Steuber, Benjamin"],["dc.contributor.author","König, Alexander Otto"],["dc.contributor.author","Lubeseder-Martellato, Clara"],["dc.contributor.author","Winter, Thore"],["dc.contributor.author","Forster, Teresa"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Reuter-Jessen, Kirsten"],["dc.contributor.author","Griesmann, Heidi"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Tsai, Wan-Chi"],["dc.contributor.author","Siveke, Jens T."],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Johnsen, Steven Arthur"],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Heßmann, Elisabeth"],["dc.date.accessioned","2018-11-07T10:24:16Z"],["dc.date.available","2018-11-07T10:24:16Z"],["dc.date.issued","2017"],["dc.description.abstract","BACKGROUND & AIMS: The ability of exocrine pancreatic cells to change the cellular phenotype is required for tissue regeneration upon injury, but also contributes to their malignant transformation and tumor progression. We investigated context-dependent signaling and transcription mechanisms that determine pancreatic cell fate decisions toward regeneration and malignancy. In particular, we studied the function and regulation of the inflammatory transcription factor nuclear factor of activated T cells 1 (NFATC1) in pancreatic cell plasticity and tissue adaptation. METHODS: We analyzed cell plasticity during pancreatic regeneration and transformation in mice with pancreas-specific expression of a constitutively active form of NFATC1, or depletion of enhancer of zeste 2 homologue 2 (EZH2), in the context of wild-type or constitutively activate Kras, respectively. Acute and chronic pancreatitis were induced by intraperitoneal injection of caerulein. EZH2-dependent regulation of NFATC1 expression was studied in mouse in human pancreatic tissue and cells by immunohistochemistry, immunoblotting, and quantitative reverse transcription polymerase chain reaction. We used genetic and pharmacologic approaches of EZH2 and NFATC1 inhibition to study the consequences of pathway disruption on pancreatic morphology and function. Epigenetic modifications on the NFATC1 gene were investigated by chromatin immunoprecipitation assays. RESULTS: NFATC1 was rapidly and transiently induced in early adaptation to acinar cell injury in human samples and in mice, where it promoted acinar cell trans-differentiation and blocked proliferation of metaplastic pancreatic cells. However, in late stages of regeneration, Nfatc1 was epigenetically silenced by EZH2-dependent histone methylation, to enable acinar cell redifferentiation and prevent organ atrophy and exocrine insufficiency. In contrast, oncogenic activation of KRAS signaling in pancreatic ductal adenocarcinoma cells reversed the EZH2-dependent effects on the NFATC1 gene and was required for EZH2-mediated transcriptional activation of NFATC1. CONCLUSIONS: In studies of human and mouse pancreatic cells and tissue, we identified context-specific epigenetic regulation of NFATc1 activity as an important mechanism of pancreatic cell plasticity. Inhibitors of EZH2 might therefore interfere with oncogenic activity of NFATC1 and be used in treatment of pancreatic ductal adenocarcinoma."],["dc.identifier.doi","10.1053/j.gastro.2017.01.043"],["dc.identifier.isi","000401811300041"],["dc.identifier.pmid","28188746"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42625"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","W B Saunders Co-elsevier Inc"],["dc.relation.issn","1528-0012"],["dc.relation.issn","0016-5085"],["dc.title","Context-Dependent Epigenetic Regulation of Nuclear Factor of Activated T Cells 1 in Pancreatic Plasticity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0153278"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Jo, Peter"],["dc.contributor.author","Koenig, Alexander O."],["dc.contributor.author","Schirmer, Markus"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Conradi, Lena-Christin"],["dc.contributor.author","Azizian, Azadeh"],["dc.contributor.author","Bernhardt, Markus"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Stroebel, Philipp"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Gaedcke, Jochen"],["dc.date.accessioned","2018-11-07T10:15:34Z"],["dc.date.available","2018-11-07T10:15:34Z"],["dc.date.issued","2016"],["dc.description.abstract","Introduction Anti-EGFR targeted therapy is of increasing importance in advanced colorectal cancer and prior KRAS mutation testing is mandatory for therapy. However, at which occasions this should be performed is still under debate. We aimed to assess in patients with locally advanced rectal cancer whether there is intra-specimen KRAS heterogeneity prior to and upon preoperative chemoradiotherapy (CRT), and if there are any changes in KRAS mutation status due to this intervention. Materials and Methods KRAS mutation status analyses were performed in 199 tumor samples from 47 patients with rectal cancer. To evaluate the heterogeneity between different tumor areas within the same tumor prior to preoperative CRT, 114 biopsies from 34 patients (mean 3 biopsies per patient) were analyzed (pre-therapeutic intratumoral heterogeneity). For the assessment of heterogeneity after CRT residual tumor tissue (85 samples) from 12 patients (mean 4.2 tissue samples per patient) were analyzed (post-therapeutic intratumoral heterogeneity) and assessment of heterogeneity before and after CRT was evaluated in corresponding patient samples (interventional heterogeneity). Primer extension method (SNaPshot (TM)) was used for initial KRAS mutation status testing for Codon 12, 13, 61, and 146. Discordant results by this method were reevaluated by using the FDA-approved KRAS Pyro Kit 24, V1 and the RAS Extension Pyro Kit 24, V1 Kit (therascreen (R) KRAS test). Results For 20 (43%) out of the 47 patients, a KRAS mutation was detected. With 12 out of 20, the majority of these mutations affected codon 35. We did not obtained evidence that CRT results in changes of the KRAS mutation pattern. In addition, no intratumoral heterogeneity in the KRAS mutational status could be proven. This was true for both the biopsies prior to CRT and the resection specimens thereafter. The discrepancy observed in some samples when using the SNaPshot (TM) assay was due to insufficient sensitivity of this technique upon massive tumor regression by CRT as application of the therascreen (R) KRAS test revealed concordant results. Conclusion Our results indicate that the KRAS mutation status at the primary tumor site of rectal cancer is homogenous. Its assessment for therapeutic decisions is feasible in pre-therapeutic biopsies as well as in post-therapeutic resected specimens. The amount of viable tumor cells seems to be an important determinant for assay sensitivity and should thus be considered for selection of the analytical method."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2016"],["dc.identifier.doi","10.1371/journal.pone.0153278"],["dc.identifier.isi","000373891000040"],["dc.identifier.pmid","27064574"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13201"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40835"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Heterogeneity of KRAS Mutation Status in Rectal Cancer"],["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.firstpage","517"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The EMBO Journal"],["dc.bibliographiccitation.lastpage","530"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Singh, Shiv K."],["dc.contributor.author","Chen, Nai-Ming"],["dc.contributor.author","Heßmann, Elisabeth"],["dc.contributor.author","Siveke, Jens T."],["dc.contributor.author","Lahmann, Marlen"],["dc.contributor.author","Singh, Garima"],["dc.contributor.author","Voelker, Nadine"],["dc.contributor.author","Vogt, Sophia"],["dc.contributor.author","Esposito, Irene"],["dc.contributor.author","Schmidt, Ansgar"],["dc.contributor.author","Brendel, Cornelia"],["dc.contributor.author","Stiewe, Thorsten"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Mernberger, Marco"],["dc.contributor.author","Crawford, Howard C."],["dc.contributor.author","Bamlet, William R."],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Li, Xiao-Kun"],["dc.contributor.author","Smyrk, Thomas C."],["dc.contributor.author","Billadeau, Daniel D."],["dc.contributor.author","Hebrok, Matthias"],["dc.contributor.author","Neeße, Albrecht"],["dc.contributor.author","Koenig, Alexander O."],["dc.contributor.author","Ellenrieder, Volker"],["dc.date.accessioned","2018-11-07T10:00:56Z"],["dc.date.available","2018-11-07T10:00:56Z"],["dc.date.issued","2015"],["dc.description.abstract","In adaptation to oncogenic signals, pancreatic ductal adenocarcinoma (PDAC) cells undergo epithelial-mesenchymal transition (EMT), a process combining tumor cell dedifferentiation with acquisition of stemness features. However, the mechanisms linking oncogene-induced signaling pathways with EMT and stemness remain largely elusive. Here, we uncover the inflammation-induced transcription factor NFATc1 as a central regulator of pancreatic cancer cell plasticity. In particular, we show that NFATc1 drives EMT reprogramming and maintains pancreatic cancer cells in a stem cell-like state through Sox2-dependent transcription of EMT and stemness factors. Intriguingly, NFATc1-Sox2 complex-mediated PDAC dedifferentiation and progression is opposed by antithetical p53-miR200c signaling, and inactivation of the tumor suppressor pathway is essential for tumor dedifferentiation and dissemination both in genetically engineered mouse models (GEMM) and human PDAC. Based on these findings, we propose the existence of a hierarchical signaling network regulating PDAC cell plasticity and suggest that the molecular decision between epithelial cell preservation and conversion into a dedifferentiated cancer stem cell-like phenotype depends on opposing levels of p53 and NFATc1 signaling activities."],["dc.identifier.doi","10.15252/embj.201489574"],["dc.identifier.isi","000349695100009"],["dc.identifier.pmid","25586376"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37913"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley"],["dc.relation.issn","1460-2075"],["dc.relation.issn","0261-4189"],["dc.title","Antithetical NFATc1-Sox2 and p53-miR200 signaling networks govern pancreatic cancer cell plasticity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e0239806"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","PLoS One"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Jo, Peter"],["dc.contributor.author","Bernhardt, Markus"],["dc.contributor.author","Nietert, Manuel"],["dc.contributor.author","König, Alexander"],["dc.contributor.author","Azizian, Azadeh"],["dc.contributor.author","Schirmer, Markus A."],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Reuter-Jessen, Kirsten"],["dc.contributor.author","Ghadimi, Michael"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.editor","Deb, Sumitra"],["dc.date.accessioned","2021-04-14T08:31:16Z"],["dc.date.available","2021-04-14T08:31:16Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1371/journal.pone.0239806"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17654"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83536"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1932-6203"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","KRAS mutation status concordance between the primary tumor and the corresponding metastasis in patients with rectal cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","80"],["dc.bibliographiccitation.journal","Case Reports in Gastroenterology"],["dc.bibliographiccitation.lastpage","88"],["dc.contributor.author","Schade, Sebastian"],["dc.contributor.author","Koenig, Ute"],["dc.contributor.author","Mekolli, Ardian"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Neesse, Albrecht"],["dc.contributor.author","Reinecke, Johanna"],["dc.contributor.author","Brunner, Marius"],["dc.contributor.author","Amir Hosseini, Ali Seif"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Stroebel, Philipp"],["dc.contributor.author","Koenig, Alexander"],["dc.date.accessioned","2022-04-01T10:01:56Z"],["dc.date.available","2022-04-01T10:01:56Z"],["dc.date.issued","2022"],["dc.description.abstract","Gastric cancer (GC) represents one of the most fatal neoplasms in gastrointestinal oncology and affected patients can only hope for cure in limited disease. In a metastatic situation however, patients have a worse prognosis finally resulting in cancer-related death. Some improvements were made by using intensified chemotherapy such as the FLOT protocol (5-FU, leucovorin, oxaliplatin and docetaxel). However, a breakthrough in the treatment of advanced GC has been achieved by pre-therapeutical tumor analysis for potentially targetable alterations. Microsatellite instability, PD-L1 expression, Epstein Barr virus, and human epidermal growth factor receptor-2 (HER2) overexpression or amplification are the most beneficial targets, if addressed, can prolong survival in a palliative situation. Whether the combination of these targeted therapeutics with chemotherapy can bring long-term survival or even a chance of cure in a metastatic situation is not clear. Here, we report the case of a 30-year-old man with GC and extensive metastases who was cured by anti-HER2 antibody Trastuzumab combined with the FLOT regime. Initial staging showed an exophytic Siewert type III tumor and extensive hepatic metastases. Histology resulted in gastric adenocarcinoma with HER2 overexpression (2+, FISH positive). Twelve courses of chemotherapy comprising Trastuzumab and FLOT were administered. After treatment, the extensive liver metastases had disappeared with no evidence of residual tumor growth on the CT scans. Monotherapy of Trastuzumab was continued until gastrectomy with D2 lymph node dissection and probing of liver tissue, which revealed no residual tumor cells. Five years after surgery, there is continued complete remission. In conclusion, Trastuzumab in combination with FLOT may have curative potential even for metastatic stages of HER-2-positive GC."],["dc.identifier.doi","10.1159/000520057"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105784"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation.eissn","1662-0631"],["dc.title","Cure Is Possible: Extensively Metastatic HER2-Positive Gastric Carcinoma with 5 years of Complete Remission after Therapy with the FLOT Regimen and Trastuzumab"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]