Hamdan, Feda Hisham Mohd

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Clinical Epigenetics"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Sen, Madhobi"],["dc.contributor.author","Wang, Xin"],["dc.contributor.author","Hamdan, Feda H."],["dc.contributor.author","Rapp, Jacobe"],["dc.contributor.author","Eggert, Jessica"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Kutschat, Ana Patricia"],["dc.contributor.author","Younesi, Fereshteh S."],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Papantonis, Argyris"],["dc.contributor.author","Strӧbel, Philipp"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2020-12-10T18:39:06Z"],["dc.date.available","2020-12-10T18:39:06Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1186/s13148-019-0690-5"],["dc.identifier.eissn","1868-7083"],["dc.identifier.issn","1868-7075"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16438"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77543"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","ARID1A facilitates KRAS signaling-regulated enhancer activity in an AP1-dependent manner in colorectal cancer cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["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"]]

[["dc.bibliographiccitation.artnumber","1142"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Cancers"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Flebbe, Hannah"],["dc.contributor.author","Hamdan, Feda H."],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Ghadimi, B. Michael"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Grade, Marian"],["dc.date.accessioned","2019-08-14T10:46:50Z"],["dc.date.available","2019-08-14T10:46:50Z"],["dc.date.issued","2019"],["dc.description.abstract","Epigenetic alterations play a central role in cancer development and progression. The acetylation of histone 3 at lysine 27 (H3K27ac) specifically marks active genes. While chromatin immunoprecipitation (ChIP) followed by next-generation sequencing (ChIP-seq) analyses are commonly performed in cell lines, only limited data are available from primary tumors. We therefore examined whether cancer-specific alterations in H3K27ac occupancy can be identified in primary rectal cancer. Tissue samples from primary rectal cancer and matched mucosa were obtained. ChIP-seq for H3K27ac was performed and differentially occupied regions were identified. The expression of selected genes displaying differential occupancy between tumor and mucosa were examined in gene expression data from an independent patient cohort. Differential expression of four proteins was further examined by immunohistochemistry. ChIP-seq for H3K27ac in primary rectal cancer and matched mucosa was successfully performed and revealed differential binding on 44 regions. This led to the identification of genes with increased H3K27ac, i.e., RIPK2, FOXQ1, KRT23, and EPHX4, which were also highly upregulated in primary rectal cancer in an independent dataset. The increased expression of these four proteins was confirmed by immunohistochemistry. This study demonstrates the feasibility of ChIP-seq-based epigenome mapping of primary rectal cancer and confirms the value of H3K27ac occupancy to predict gene expression differences."],["dc.identifier.doi","10.3390/cancers11081142"],["dc.identifier.pmid","31404997"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16348"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62383"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.issn","2072-6694"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Epigenome Mapping Identifies Tumor-Specific Gene Expression in Primary Rectal Cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]