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.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","229"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Cellular Oncology"],["dc.bibliographiccitation.lastpage","230"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Kendziorra, Emil"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Emons, G."],["dc.contributor.author","Ahlborn, Kerstin"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Rave-Fränk, Margret"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Becker, H."],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Ried, Thomas"],["dc.contributor.author","Grade, Marian"],["dc.date.accessioned","2018-11-07T08:47:17Z"],["dc.date.available","2018-11-07T08:47:17Z"],["dc.date.issued","2010"],["dc.identifier.isi","000276461900140"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20910"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Ios Press"],["dc.publisher.place","Amsterdam"],["dc.relation.conference","Congress of the International-Society-for-Cellular-Oncology"],["dc.relation.eventlocation","Dresden, GERMANY"],["dc.relation.issn","1570-5870"],["dc.title","RNAi-MEDIATED SILENCING OF TCF7L2 SENSITIZES COLORECTAL CANCER CELLS TO RADIATION"],["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","Kendziorra, Emil"],["dc.contributor.author","Ahlborn, Kerstin"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Rave-Fränk, Margret"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Emons, Georg"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Ebner, Reinhard"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Ried, Thomas"],["dc.contributor.author","Grade, Marian"],["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.AM2011-2490"],["dc.identifier.isi","000209701302028"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23287"],["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","Silencing of TCF7L2 sensitizes Wnt/beta-catenin signaling-dependent colorectal cancer cells to radiation"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","164"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Cellular Oncology"],["dc.bibliographiccitation.lastpage","165"],["dc.bibliographiccitation.volume","32"],["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","Hoermann, Patrick"],["dc.contributor.author","Ebner, Reinhard"],["dc.contributor.author","Becker, H."],["dc.contributor.author","Difilippantonio, Michael J."],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Caplen, Natasha J."],["dc.contributor.author","Ried, Thomas"],["dc.date.accessioned","2018-11-07T08:47:16Z"],["dc.date.available","2018-11-07T08:47:16Z"],["dc.date.issued","2010"],["dc.identifier.isi","000276461900019"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20906"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Ios Press"],["dc.publisher.place","Amsterdam"],["dc.relation.conference","Congress of the International-Society-for-Cellular-Oncology"],["dc.relation.eventlocation","Dresden, GERMANY"],["dc.relation.issn","1570-5870"],["dc.title","A COMBINED FUNCTIONAL AND SYSTEMS BIOLOGY APPROACH IDENTIFIES COLORECTAL CANCER GENES AS NOVEL POTENTIAL THERAPEUTIC TARGETS"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","997"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","International Journal of Cancer"],["dc.bibliographiccitation.lastpage","1007"],["dc.bibliographiccitation.volume","134"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Roesler, Birte"],["dc.contributor.author","Bielfeld, Christian"],["dc.contributor.author","Emons, Georg"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Rave-Fränk, Margret"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Ebner, Reinhard"],["dc.contributor.author","Ried, Thomas"],["dc.contributor.author","Grade, Marian"],["dc.date.accessioned","2018-11-07T09:44:52Z"],["dc.date.available","2018-11-07T09:44:52Z"],["dc.date.issued","2014"],["dc.description.abstract","Increased activity of signal transducer and activator of transcription 3 (STAT3) is common in human malignancies, including colorectal cancers (CRCs). We have recently reported that STAT3 gene expression correlates with resistance of CRC cell lines to 5-fluorouracil (5-FU)-based chemoradiotherapy (CT/RT). This is of considerable clinical importance, because a large proportion of rectal cancers are resistant to preoperative multimodal treatment. To test whether STAT3 contributes to CT/RT-resistance, we first confirmed that STAT3 protein expression correlated positively with increasing resistance. While STAT3 was not constitutively active, stimulation with interleukin-6 (IL-6) resulted in remarkably higher expression levels of phosphorylated STAT3 in CT/RT-resistant cell lines. A similar result was observed when we determined IL-6-induced expression levels of phosphorylated STAT3 following irradiation. Next, STAT3 was inhibited in SW480 and SW837 using siRNA, shRNA and the small-molecule inhibitor STATTIC. Successful silencing and inhibition of phosphorylation was confirmed using Western blot analysis and a luciferase reporter assay. RNAi-mediated silencing as well as STATTIC treatment resulted in significantly decreased clonogenic survival following exposure to 3 mu M of 5-FU and irradiation in a dose-dependent manner, with dose-modifying factors of 1.3-2.5 at a surviving fraction of 0.37. Finally, STAT3 inhibition led to a profound CT/RT-sensitization in a subcutaneous xenograft model, with a significantly delayed tumor regrowth in STATTIC-treated mice compared with control animals. These results highlight a potential role of STAT3 in mediating treatment resistance and provide first proof of concept that STAT3 represents a promising novel molecular target for sensitizing resistant rectal cancers to CT/RT. What's new? A considerable percentage of rectal cancers are resistant to preoperative chemoradiotherapy, which exposes patients to the potential side effects of both irradiation and chemotherapy without clear benefits. In this study, IL-6-stimulated expression levels of phosphorylated STAT3 were remarkably higher in chemoradiotherapy-resistant colorectal cancer cell lines. RNAi- and small molecule-mediated STAT3 inhibition sensitized to chemoradiotherapy in vitro in a dose-dependent manner, which led to a profound chemoradiotherapy-sensitization in a subcutaneous xenograft model. These results highlight a potential role of STAT3 in treatment resistance, and provide first proof of concept that STAT3 represents a promising novel molecular target for sensitizing resistant rectal cancers to chemoradiotherapy."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaf [KFO 179: GR 3376/1-1, GR 3376/1-2]"],["dc.identifier.doi","10.1002/ijc.28429"],["dc.identifier.isi","000327889700029"],["dc.identifier.pmid","23934972"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34492"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1097-0215"],["dc.relation.issn","0020-7136"],["dc.title","STAT3 inhibition sensitizes colorectal cancer to chemoradiotherapy in vitro and in vivo"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]