Spitzner, Melanie

[["dc.bibliographiccitation.journal","Cancer Research"],["dc.bibliographiccitation.volume","72"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Roesler, Birte"],["dc.contributor.author","Bielfeld, Christian"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Rave-Fränk, Margret"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Ried, Thomas"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Grade, Marian"],["dc.date.accessioned","2018-11-07T09:11:10Z"],["dc.date.available","2018-11-07T09:11:10Z"],["dc.date.issued","2012"],["dc.identifier.doi","10.1158/1538-7445.AM2012-3446"],["dc.identifier.isi","000209701502014"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26663"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.publisher.place","Philadelphia"],["dc.title","Stat3 is a potential molecular target for chemoradiosensitization of colorectal cancer cells"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","EJC SUPPLEMENTS"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Hummon, Amanda B."],["dc.contributor.author","Camps, Jordi"],["dc.contributor.author","Emons, G."],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Difilippantonio, Michael J."],["dc.contributor.author","Ghadimi, B. Michael"],["dc.contributor.author","Caplen, Natasha J."],["dc.contributor.author","Ried, Thomas"],["dc.date.accessioned","2018-11-07T11:10:28Z"],["dc.date.available","2018-11-07T11:10:28Z"],["dc.date.issued","2008"],["dc.format.extent","174"],["dc.identifier.doi","10.1016/S1359-6349(08)72485-6"],["dc.identifier.isi","000261221200548"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53216"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.publisher.place","Oxford"],["dc.relation.conference","20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics"],["dc.relation.eventlocation","Geneva, SWITZERLAND"],["dc.relation.issn","1359-6349"],["dc.title","RNAi-based identification of potential targets in colorectal cancers"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Cancer Research"],["dc.bibliographiccitation.volume","71"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Emons, Georg"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Rave-Fränk, Margret"],["dc.contributor.author","Scharf, Jens-Gerd"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Ried, Thomas"],["dc.date.accessioned","2018-11-07T08:57:01Z"],["dc.date.available","2018-11-07T08:57:01Z"],["dc.date.issued","2011"],["dc.identifier.doi","10.1158/1538-7445.AM2011-2508"],["dc.identifier.isi","000209701302047"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23286"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.publisher.place","Philadelphia"],["dc.relation.issn","1538-7445"],["dc.relation.issn","0008-5472"],["dc.title","Identification of potential relevant pathways and genes for resistance to chemoradiotherapy in colorectal cancer cells"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1481"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Molecular Cancer Research"],["dc.bibliographiccitation.lastpage","1490"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Emons, Georg"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Reineke, Sebastian"],["dc.contributor.author","Möller, Janneke"],["dc.contributor.author","Auslander, Noam"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Hu, Yue"],["dc.contributor.author","Beissbarth, Tim"],["dc.contributor.author","Wolff, Hendrik A."],["dc.contributor.author","Rave-Fränk, Margret"],["dc.contributor.author","Heßmann, Elisabeth"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Ghadimi, B. Michael"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Ried, Thomas"],["dc.contributor.author","Grade, Marian"],["dc.date.accessioned","2020-12-10T18:37:47Z"],["dc.date.available","2020-12-10T18:37:47Z"],["dc.date.issued","2017"],["dc.description.abstract","Activation of Wnt/β-catenin signaling plays a central role in the development and progression of colorectal cancer. The Wnt-transcription factor, TCF7L2, is overexpressed in primary rectal cancers that are resistant to chemoradiotherapy and TCF7L2 mediates resistance to chemoradiotherapy. However, it is unclear whether the resistance is mediated by a TCF7L2 inherent mechanism or Wnt/β-catenin signaling in general. Here, inhibition of β-catenin by siRNAs or a small-molecule inhibitor (XAV-939) resulted in sensitization of colorectal cancer cells to chemoradiotherapy. To investigate the potential role of Wnt/β-catenin signaling in controlling therapeutic responsiveness, nontumorigenic RPE-1 cells were stimulated with Wnt-3a, a physiologic ligand of Frizzled receptors, which increased resistance to chemoradiotherapy. This effect could be recapitulated by overexpression of a degradation-resistant mutant of β-catenin (S33Y), also boosting resistance of RPE-1 cells to chemoradiotherapy, which was, conversely, abrogated by siRNA-mediated silencing of β-catenin. Consistent with these findings, higher expression levels of active β-catenin were observed as well as increased TCF/LEF reporter activity in SW1463 cells that evolved radiation resistance due to repeated radiation treatment. Global gene expression profiling identified several altered pathways, including PPAR signaling and other metabolic pathways, associated with cellular response to radiation. In summary, aberrant activation of Wnt/β-catenin signaling not only regulates the development and progression of colorectal cancer, but also mediates resistance of rectal cancers to chemoradiotherapy.Implications: Targeting Wnt/β-catenin signaling or one of the downstream pathways represents a promising strategy to increase response to chemoradiotherapy. Mol Cancer Res; 15(11); 1481-90. ©2017 AACR."],["dc.identifier.doi","10.1158/1541-7786.MCR-17-0205"],["dc.identifier.eissn","1557-3125"],["dc.identifier.issn","1541-7786"],["dc.identifier.pmid","28811361"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77090"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation.eissn","1557-3125"],["dc.relation.issn","1541-7786"],["dc.title","Chemoradiotherapy Resistance in Colorectal Cancer Cells is Mediated by Wnt/β-catenin Signaling"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","EJC SUPPLEMENTS"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Kendziorra, Emil"],["dc.contributor.author","Ahlborn, Kerstin"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Rave-Fraenk, Margret"],["dc.contributor.author","Becker, H."],["dc.contributor.author","Ghadimi, B. Michael"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Ried, Thomas"],["dc.date.accessioned","2018-11-07T08:37:08Z"],["dc.date.available","2018-11-07T08:37:08Z"],["dc.date.issued","2010"],["dc.format.extent","97"],["dc.identifier.doi","10.1016/S1359-6349(10)72008-5"],["dc.identifier.isi","000288460100295"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18461"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.publisher.place","Oxford"],["dc.relation.conference","22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics"],["dc.relation.eventlocation","Berlin, GERMANY"],["dc.relation.issn","1359-6349"],["dc.title","Silencing of TCF7L2 sensitizes colorectal cancer cells to radiation therapy"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","451"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Radiotherapy and Oncology"],["dc.bibliographiccitation.lastpage","457"],["dc.bibliographiccitation.volume","108"],["dc.contributor.author","Salendo, Junius"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Zhang, X."],["dc.contributor.author","Jo, Peter"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Kaulfuß, Silke"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Dobbelstein, Matthias"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Gaedcke, Jochen"],["dc.date.accessioned","2018-11-07T09:20:18Z"],["dc.date.available","2018-11-07T09:20:18Z"],["dc.date.issued","2013"],["dc.description.abstract","Background and purpose: Preoperative chemoradiotherapy (CRT) represents the standard treatment for locally advanced rectal cancer. Tumor response and progression vary considerably. MicroRNAs represent master regulators of gene expression, and may therefore contribute to this diversity. Material and methods: Genome-wide microRNA (miRNA) profiling was performed for 12 colorectal cancer (CRC) cell lines and an individual in vitro signature of chemoradiosensitivity was established. Functional relevance of selected miRNAs was established by transfecting miRNA-mimics into SW480 and SW837 cells. The prognostic value of selected miRNAs was assessed in 128 pretherapeutic patient biopsies. Results: Thirty-six miRNAs were identified to significantly correlate with sensitivity to CRT (Q < 0.05) including miR-320a and other miRNAs involved in the MAPK-, TGF- and Wnt-pathway. Transfection of selected miRNAs (let-7g, miR-132, miR-224, miR-320a) each induced a shift of sensitivity. High expression of let-7g was associated with a good prognosis in rectal cancer patients (P = 0.03). Conclusions: This is the first report of a miRNA expression signature for in vitro chemoradiosensitivity of cell lines. Many of the identified miRNAs have not been linked to the response to CRT and may represent potential molecular targets to sensitize resistant cancers. If further validated, let7g expression may serve as predictive biomarker. (C) 2013 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 108 (2013) 451-457"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [KFO 179]"],["dc.identifier.doi","10.1016/j.radonc.2013.06.032"],["dc.identifier.isi","000327004700015"],["dc.identifier.pmid","23932154"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28850"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Ireland Ltd"],["dc.publisher.place","Clare"],["dc.relation.conference","13th International Wolfsberg Meeting on Molecular Radiation Biology/Oncology"],["dc.relation.eventlocation","Ermatingen, SWITZERLAND"],["dc.relation.issn","0167-8140"],["dc.title","Identification of a microRNA expression signature for chemoradiosensitivity of colorectal cancer cells, involving miRNAs-320a,-224,-132 and let7g"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Oncology Research and Treatment"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Roesler, Birte"],["dc.contributor.author","Bielfeld, Christian"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Ghadimi, Michael B."],["dc.date.accessioned","2018-11-07T09:44:11Z"],["dc.date.available","2018-11-07T09:44:11Z"],["dc.date.issued","2014"],["dc.identifier.isi","000332306700320"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34336"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.publisher.place","Basel"],["dc.title","Targeting STAT3 as a therapeutic strategy to sensitize colorectal cancer to chemoradiotherapy"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Cancer Research"],["dc.bibliographiccitation.volume","72"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Eimer, Christine"],["dc.contributor.author","Emons, Georg"],["dc.contributor.author","Kendziorra, Emil"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Ried, Thomas"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Ghadimi, Michael B."],["dc.date.accessioned","2018-11-07T09:11:10Z"],["dc.date.available","2018-11-07T09:11:10Z"],["dc.date.issued","2012"],["dc.identifier.doi","10.1158/1538-7445.AM2012-5729"],["dc.identifier.isi","209701500032"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26661"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.publisher.place","Philadelphia"],["dc.title","The Wnt transcription factor TCF4 mediates resistance of colorectal cancer cells to (chemo-) radiotherapy in a beta-catenin independent manner"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1184"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","International Journal of Radiation Oncology*Biology*Physics"],["dc.bibliographiccitation.lastpage","1192"],["dc.bibliographiccitation.volume","78"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Emons, Georg"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Rave-Fränk, Margret"],["dc.contributor.author","Scharf, Jens-Gerd"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Ried, Thomas"],["dc.contributor.author","Grade, Marian"],["dc.date.accessioned","2018-11-07T08:36:51Z"],["dc.date.available","2018-11-07T08:36:51Z"],["dc.date.issued","2010"],["dc.description.abstract","Purpose: The standard treatment of patients with locally advanced rectal cancers comprises preoperative 5-fluorouracil based chemoradiotherapy followed by standardized surgery. However, tumor response to multimodal treatment has varied greatly, ranging from complete resistance to complete pathologic regression. The prediction of the response is, therefore, an important clinical need. Methods and Materials: To establish in vitro models for studying the molecular basis of this heterogeneous tumor response, we exposed 12 colorectal cancer cell lines to 3 mu M of 5-fluorouracil and 2 Gy of radiation. The differences in treatment sensitivity were then correlated with the pretherapeutic gene expression profiles of these cell lines. Results: We observed a heterogeneous response, with surviving fractions ranging from 0.28 to 0.81, closely recapitulating clinical reality. Using a linear model analysis, we identified 4,796 features whose expression levels correlated significantly with the sensitivity to chemoradiotherapy (Q < .05), including many genes involved in the mitogen-activated protein kinase signaling pathway or cell cycle genes. These data have suggested a potential relevance of the insulin and Wnt signaling pathways for treatment response, and we identified STAT3, RASSF1, DOK3, and ERBB2 as potential therapeutic targets. The microarray measurements were independently validated for a subset of these genes using real-time polymerase chain reactions. Conclusion: We are the first to report a gene expression signature for the in vitro chemoradiosensitivity of colorectal cancer cells. We anticipate that this analysis will unveil molecular biomarkers predictive of the response of rectal cancers to chemoradiotherapy and enable the identification of genes that could serve as targets to sensitize a priori resistant primary tumors. (C) 2010 Elsevier Inc."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [KFO 179]"],["dc.identifier.doi","10.1016/j.ijrobp.2010.06.023"],["dc.identifier.isi","000283963100030"],["dc.identifier.pmid","20970032"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6106"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18405"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","0360-3016"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","A GENE EXPRESSION SIGNATURE FOR CHEMORADIOSENSITIVITY OF COLORECTAL CANCER CELLS"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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"]]