Neeße, Albrecht

[["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"]]

[["dc.bibliographiccitation.artnumber","e000258"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","BMJ Open Gastroenterology"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Mavropoulou, Eirini"],["dc.contributor.author","Ternes, Kristin"],["dc.contributor.author","Mechie, Nicolae-Catalin"],["dc.contributor.author","Bremer, Sebastian Christopher Benjamin"],["dc.contributor.author","Kunsch, Steffen"],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Neesse, Albrecht"],["dc.contributor.author","Amanzada, Ahmad"],["dc.date.accessioned","2019-07-09T11:50:10Z"],["dc.date.available","2019-07-09T11:50:10Z"],["dc.date.issued","2019"],["dc.description.abstract","Background Concurrent cytomegalovirus (CMV) colitis in inflammatory bowel disease (IBD) and after haematopoietic stem cell transplantation (HSCT) is an important clinical entity associated with high rates of morbidity and mortality. Methods A retrospective study of 47 patients with IBD and 61 HSCT patients was performed regarding the evaluation of diagnostic accuracy of applied methods, predictors, risk factors for CMV disease manifestation, the proportion of patients with antiviral treatment and disease outcome. Results The sensitivity of quantitative PCR (qPCR) with a cut-off value of >250 copies/mg for CMV colitis in patients with IBD and HSCT patients was 79% and 92%, respectively. Predictors for CMV colitis in the IBD cohort were anaemia and the presence of endoscopic ulcers. Glucocorticoids, calcineurin inhibitors and >2 concurrent lines of treatment with immunosuppressive drugs could be identified as risk factors for CMV colitis in the IBD cohort with an OR of 7.1 (95% CI 1.7 to 29.9), 21.3 (95% CI 2.4 to 188.7) and 13.4 (95% CI 3.2 to 56.1), respectively. Predictors and risk factors for CMV gastroenteritis in the HSCT cohort was the presence of endoscopic ulcers (OR 18.6, 95% CI 3.3 to 103.7) and >2 concurrent lines of treatment with immunosuppressive drugs. Antiviral therapy was administered in 70% of patients with IBD and 77% of HSCT patients with CMV disease. 71% of antiviraltreated patients with IBD showed an improvement of their disease activity and 14% underwent colectomy. The mortality rate of HSCT patients was 21% irrespective of their CMV status. Conclusions In addition to the implementation of histological methods, qPCR may be performed in patients with suspected high-risk IBD and HSCT patients for CMV colitis. Independent validations of these results in further prospective studies are needed."],["dc.identifier.doi","10.1136/bmjgast-2018-000258"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15876"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59717"],["dc.language.iso","en"],["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.subject.ddc","610"],["dc.title","Cytomegalovirus colitis in inflammatory bowel disease and after haematopoietic stem cell transplantation: diagnostic accuracy, predictors, risk factors and disease outcome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]