Heßmann, Elisabeth

[["dc.bibliographiccitation.firstpage","688"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Cancer Discovery"],["dc.bibliographiccitation.lastpage","701"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Baumgart, Sandra"],["dc.contributor.author","Chen, Nai-Ming"],["dc.contributor.author","Siveke, Jens T."],["dc.contributor.author","Koenig, Alexander O."],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Singh, Shiv K."],["dc.contributor.author","Wolf, Elmar"],["dc.contributor.author","Bartkuhn, Marek"],["dc.contributor.author","Esposito, Irene"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Reinecke, Johanna"],["dc.contributor.author","Nikorowitsch, Julius"],["dc.contributor.author","Brunner, Marius"],["dc.contributor.author","Singh, Garima"],["dc.contributor.author","Fernandez-Zapico, Martin E."],["dc.contributor.author","Smyrk, Thomas C."],["dc.contributor.author","Bamlet, William R."],["dc.contributor.author","Eilers, Martin"],["dc.contributor.author","Neesse, Albrecht"],["dc.contributor.author","Gress, Thomas M."],["dc.contributor.author","Billadeau, Daniel D."],["dc.contributor.author","Tuveson, David A."],["dc.contributor.author","Urrutia, Raul"],["dc.contributor.author","Ellenrieder, Volker"],["dc.date.accessioned","2018-11-07T09:39:31Z"],["dc.date.available","2018-11-07T09:39:31Z"],["dc.date.issued","2014"],["dc.description.abstract","Cancer-associated inflammation is a molecular key feature in pancreatic ductal adenocarcinoma. Oncogenic KRAS in conjunction with persistent inflammation is known to accelerate carcinogenesis, although the underlying mechanisms remain poorly understood. Here, we outline a novel pathway whereby the transcription factors NFATc1 and STAT3 cooperate in pancreatic epithelial cells to promote Kras(G12D) -driven carcinogenesis. NFATc1 activation is induced by inflammation and itself accelerates inflammation-induced carcinogenesis in Kras(G12D) mice, whereas genetic or pharmacologic ablation of NFATc1 attenuates this effect. Mechanistically, NFATc1 complexes with STAT3 for enhancer-promoter communications at jointly regulated genes involved in oncogenesis, for example, Cyclin, EGFR and WNT family members. The NFATc1-STAT3 cooperativity is operative in pancreatitis-mediated carcinogenesis as well as in established human pancreatic cancer. Together, these studies unravel new mechanisms of inflammatory-driven pancreatic carcinogenesis and suggest beneficial effects of chemopreventive strategies using drugs that are currently available for targeting these factors in clinical trials. SIGNIFICANCE: Our study points to the existence of an oncogenic NFATc1-STAT3 cooperativity that mechanistically links inflammation with pancreatic cancer initiation and progression. Because NFATc1STAT3 nucleoprotein complexes control the expression of gene networks at the intersection of inflammation and cancer, our study has significant relevance for potentially managing pancreatic cancer and other inflammatory-driven malignancies. (C) 2014 AACR."],["dc.identifier.doi","10.1158/2159-8290.CD-13-0593"],["dc.identifier.isi","000337185500025"],["dc.identifier.pmid","24694735"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33304"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","2159-8290"],["dc.relation.issn","2159-8274"],["dc.title","Inflammation-Induced NFATc1-STAT3 Transcription Complex Promotes Pancreatic Cancer Initiation by Kras(G12D)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4620"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","Cancer Research"],["dc.bibliographiccitation.lastpage","4632"],["dc.bibliographiccitation.volume","80"],["dc.contributor.author","Patil, Shilpa"],["dc.contributor.author","Steuber, Benjamin"],["dc.contributor.author","Kopp, Waltraut"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Urbach, Laura"],["dc.contributor.author","Wang, Xin"],["dc.contributor.author","Küffer, Stefan"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Spyropoulou, Dimitra"],["dc.contributor.author","Zhang, Zhe"],["dc.contributor.author","Versemann, Lennart"],["dc.contributor.author","Bösherz, Mark Sebastian"],["dc.contributor.author","Brunner, Marius"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Zhang, Jin-San"],["dc.contributor.author","Neesse, Albrecht"],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Singh, Shiv K."],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Hessmann, Elisabeth"],["dc.date.accessioned","2021-04-14T08:31:24Z"],["dc.date.available","2021-04-14T08:31:24Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1158/0008-5472.CAN-20-0672"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83584"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1538-7445"],["dc.relation.issn","0008-5472"],["dc.title","EZH2 Regulates Pancreatic Cancer Subtype Identity and Tumor Progression via Transcriptional Repression of GATA6"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","394"],["dc.bibliographiccitation.journal","EBioMedicine"],["dc.bibliographiccitation.lastpage","405"],["dc.bibliographiccitation.volume","40"],["dc.contributor.author","Patzak, Melanie S."],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Patil, Shilpa"],["dc.contributor.author","Hamdan, Feda H."],["dc.contributor.author","Goetze, Robert G."],["dc.contributor.author","Brunner, Marius"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Jodrell, Duncan I."],["dc.contributor.author","Richards, Frances M."],["dc.contributor.author","Pilarsky, Christian"],["dc.contributor.author","Gruetzmann, Robert"],["dc.contributor.author","Rümmele, Petra"],["dc.contributor.author","Knösel, Thomas"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Neesse, Albrecht"],["dc.date.accessioned","2019-07-09T11:50:10Z"],["dc.date.available","2019-07-09T11:50:10Z"],["dc.date.issued","2019"],["dc.description.abstract","BACKGROUND: Cytosolic 5'-nucleotidase 1A (NT5C1A) dephosphorylates non-cyclic nucleoside monophosphates to produce nucleosides and inorganic phosphates. Here, we investigate NT5C1A expression in pancreatic ductal adenocarcinoma (PDAC) and its impact on gemcitabine metabolism and therapeutic efficacy. METHODS: NT5C1A expression was determined by semiquantitative immunohistochemistry using tissue microarrays. Gemcitabine metabolites and response were assessed in several human and murine PDAC cell lines using crystal violet assays, Western blot, viability assays, and liquid chromatography tandem mass-spectrometry (LC-MS/MS). FINDINGS: NT5C1A was strongly expressed in tumor cells of a large subgroup of resected PDAC patients in two independent patient cohorts (44-56% score 2 and 8-26% score 3, n = 414). In contrast, NT5C1A was expressed at very low levels in the tumor stroma, and neither stromal nor tumoral expression was a prognostic marker for postoperative survival. In vitro, NT5C1A overexpression increased gemcitabine resistance by reducing apoptosis levels and significantly decreased intracellular amounts of cytotoxic dFdCTP in +NT5C1A tumor cells. Co-culture experiments with conditioned media from +NT5C1A PSCs improved gemcitabine efficacy in tumor cells. In vivo, therapeutic efficacy of gemcitabine was significantly decreased and serum levels of the inactive gemcitabine metabolite dFdU significantly increased in mice bearing NT5C1A overexpressing tumors. INTERPRETATION: NT5C1A is robustly expressed in tumor cells of resected PDAC patients. Moreover, NT5C1A mediates gemcitabine resistance by decreasing the amount of intracellular dFdCTP, leading to reduced tumor cell apoptosis and larger pancreatic tumors in mice. Further studies should clarify the role of NT5C1A as novel predictor for gemcitabine treatment response in patients with PDAC."],["dc.identifier.doi","10.1016/j.ebiom.2019.01.037"],["dc.identifier.pmid","30709769"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15875"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59716"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2352-3964"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.subject.ddc","610"],["dc.title","Cytosolic 5'-nucleotidase 1A is overexpressed in pancreatic cancer and mediates gemcitabine resistance by reducing intracellular gemcitabine metabolites."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]