Emons, Georg

[["dc.bibliographiccitation.artnumber","36"],["dc.bibliographiccitation.journal","BMC Medical Genomics"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Opitz, Lennart"],["dc.contributor.author","Salinas-Riester, Gabriela"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Jung, Klaus"],["dc.contributor.author","Jo, Peter"],["dc.contributor.author","Emons, Georg"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Gaedcke, Jochen"],["dc.date.accessioned","2018-11-07T08:40:26Z"],["dc.date.available","2018-11-07T08:40:26Z"],["dc.date.issued","2010"],["dc.description.abstract","Background: Gene expression profiling is a highly sensitive technique which is used for profiling tumor samples for medical prognosis. RNA quality and degradation influence the analysis results of gene expression profiles. The impact of this influence on the profiles and its medical impact is not fully understood. As patient samples are very valuable for clinical studies, it is necessary to establish criteria for the RNA quality to be able to use these samples in later analysis. Methods: To investigate the effects of RNA integrity on gene expression profiling, whole genome expression arrays were used. We used tumor biopsies from patients diagnosed with locally advanced rectal cancer. To simulate degradation, the isolated total RNA of all patients was subjected to heat-induced degradation in a time-dependent manner. Expression profiling was then performed and data were analyzed bioinformatically to assess the differences. Results: The differences introduced by RNA degradation were largely outweighed by the biological differences between the patients. Only a relatively small number of probes (275 out of 41,000) show a significant effect due to degradation. The genes that show the strongest effect due to RNA degradation were, especially, those with short mRNAs and probe positions near the 5' end. Conclusions: Degraded RNA from tumor samples (RIN > 5) can still be used to perform gene expression analysis. A much higher biological variance between patients is observed compared to the effect that is imposed by degradation of RNA. Nevertheless there are genes, very short ones and those with the probe binding side close to the 5' end that should be excluded from gene expression analysis when working with degraded RNA. These results are limited to the Agilent 44 k microarray platform and should be carefully interpreted when transferring to other settings."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [KFO 179]; BMBF [01GS0890]; BreastSys"],["dc.identifier.doi","10.1186/1755-8794-3-36"],["dc.identifier.isi","000283179600001"],["dc.identifier.pmid","20696062"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5664"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19230"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1755-8794"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Impact of RNA degradation on gene expression profiling"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["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","10301"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","22"],["dc.contributor.affiliation","Spitzner, Melanie; 1Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, Germany; melanie.spitzner@med.uni-goettingen.de (M.S.); georg.emons@med.uni-goettingen.de (G.E.); karlburkhard.schuetz@sanktgeorg.de (K.B.S.); mghadim@uni-goettingen.de (B.M.G.); guenter.schneider@med.uni-goettingen.de (G.S.)"],["dc.contributor.affiliation","Emons, Georg; 1Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, Germany; melanie.spitzner@med.uni-goettingen.de (M.S.); georg.emons@med.uni-goettingen.de (G.E.); karlburkhard.schuetz@sanktgeorg.de (K.B.S.); mghadim@uni-goettingen.de (B.M.G.); guenter.schneider@med.uni-goettingen.de (G.S.)"],["dc.contributor.affiliation","Schütz, Karl Burkhard; 1Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, Germany; melanie.spitzner@med.uni-goettingen.de (M.S.); georg.emons@med.uni-goettingen.de (G.E.); karlburkhard.schuetz@sanktgeorg.de (K.B.S.); mghadim@uni-goettingen.de (B.M.G.); guenter.schneider@med.uni-goettingen.de (G.S.)"],["dc.contributor.affiliation","Wolff, Hendrik A.; 3Department of Radiotherapy and Radiooncology, University Medical Center Goettingen, 37075 Goettingen, Germany; h.wolff@strahlentherapie-muenchen.eu (H.A.W.); stefan.rieken@med.uni-goettingen.de (S.R.)"],["dc.contributor.affiliation","Rieken, Stefan; 3Department of Radiotherapy and Radiooncology, University Medical Center Goettingen, 37075 Goettingen, Germany; h.wolff@strahlentherapie-muenchen.eu (H.A.W.); stefan.rieken@med.uni-goettingen.de (S.R.)"],["dc.contributor.affiliation","Ghadimi, B. Michael; 1Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, Germany; melanie.spitzner@med.uni-goettingen.de (M.S.); georg.emons@med.uni-goettingen.de (G.E.); karlburkhard.schuetz@sanktgeorg.de (K.B.S.); mghadim@uni-goettingen.de (B.M.G.); guenter.schneider@med.uni-goettingen.de (G.S.)"],["dc.contributor.affiliation","Schneider, Günter; 1Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, Germany; melanie.spitzner@med.uni-goettingen.de (M.S.); georg.emons@med.uni-goettingen.de (G.E.); karlburkhard.schuetz@sanktgeorg.de (K.B.S.); mghadim@uni-goettingen.de (B.M.G.); guenter.schneider@med.uni-goettingen.de (G.S.)"],["dc.contributor.affiliation","Grade, Marian; 1Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, Germany; melanie.spitzner@med.uni-goettingen.de (M.S.); georg.emons@med.uni-goettingen.de (G.E.); karlburkhard.schuetz@sanktgeorg.de (K.B.S.); mghadim@uni-goettingen.de (B.M.G.); guenter.schneider@med.uni-goettingen.de (G.S.)"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Emons, Georg"],["dc.contributor.author","Schütz, Karl Burkhard"],["dc.contributor.author","Wolff, Hendrik A."],["dc.contributor.author","Rieken, Stefan"],["dc.contributor.author","Ghadimi, B. Michael"],["dc.contributor.author","Schneider, Günter"],["dc.contributor.author","Grade, Marian"],["dc.date.accessioned","2021-12-01T09:23:14Z"],["dc.date.available","2021-12-01T09:23:14Z"],["dc.date.issued","2021"],["dc.date.updated","2022-09-03T10:10:11Z"],["dc.description.abstract","The standard treatment of locally advanced esophageal cancer comprises multimodal treatment concepts including preoperative chemoradiotherapy (CRT) followed by radical surgical resection. However, despite intensified treatment approaches, 5-year survival rates are still low. Therefore, new strategies are required to overcome treatment resistance, and to improve patients’ outcome. In this study, we investigated the impact of Wnt/β-catenin signaling on CRT resistance in esophageal cancer cells. Experiments were conducted in adenocarcinoma and squamous cell carcinoma cell lines with varying expression levels of Wnt proteins and Wnt/β-catenin signaling activities. To investigate the effect of Wnt/β-catenin signaling on CRT responsiveness, we genetically or pharmacologically inhibited Wnt/β-catenin signaling. Our experiments revealed that inhibition of Wnt/β-catenin signaling sensitizes cell lines with robust pathway activity to CRT. In conclusion, Wnt/β-catenin activity may guide precision therapies in esophageal carcinoma patients."],["dc.description.abstract","The standard treatment of locally advanced esophageal cancer comprises multimodal treatment concepts including preoperative chemoradiotherapy (CRT) followed by radical surgical resection. However, despite intensified treatment approaches, 5-year survival rates are still low. Therefore, new strategies are required to overcome treatment resistance, and to improve patients’ outcome. In this study, we investigated the impact of Wnt/β-catenin signaling on CRT resistance in esophageal cancer cells. Experiments were conducted in adenocarcinoma and squamous cell carcinoma cell lines with varying expression levels of Wnt proteins and Wnt/β-catenin signaling activities. To investigate the effect of Wnt/β-catenin signaling on CRT responsiveness, we genetically or pharmacologically inhibited Wnt/β-catenin signaling. Our experiments revealed that inhibition of Wnt/β-catenin signaling sensitizes cell lines with robust pathway activity to CRT. In conclusion, Wnt/β-catenin activity may guide precision therapies in esophageal carcinoma patients."],["dc.identifier.doi","10.3390/ijms221910301"],["dc.identifier.pii","ijms221910301"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94598"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation.eissn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Inhibition of Wnt/β-Catenin Signaling Sensitizes Esophageal Cancer Cells to Chemoradiotherapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1"],["dc.bibliographiccitation.journal","Molecular Cancer"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Hummon, Amanda B."],["dc.contributor.author","Pitt, Jason J."],["dc.contributor.author","Camps, Jordi"],["dc.contributor.author","Emons, Georg"],["dc.contributor.author","Skube, Susan B."],["dc.contributor.author","Huppi, Konrad"],["dc.contributor.author","Jones, Tamara L."],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Difilippantonio, Michael J."],["dc.contributor.author","Ried, Thomas"],["dc.contributor.author","Caplen, Natasha J."],["dc.date.accessioned","2018-11-07T09:14:27Z"],["dc.date.available","2018-11-07T09:14:27Z"],["dc.date.issued","2012"],["dc.description.abstract","Background: Colorectal carcinomas (CRC) carry massive genetic and transcriptional alterations that influence multiple cellular pathways. The study of proteins whose loss-of-function (LOF) alters the growth of CRC cells can be used to further understand the cellular processes cancer cells depend upon for survival. Results: A small-scale RNAi screen of similar to 400 genes conducted in SW480 CRC cells identified several candidate genes as required for the viability of CRC cells, most prominently CASP8AP2/FLASH. To understand the function of this gene in maintaining the viability of CRC cells in an unbiased manner, we generated gene specific expression profiles following RNAi. Silencing of CASP8AP2/FLASH resulted in altered expression of over 2500 genes enriched for genes associated with cellular growth and proliferation. Loss of CASP8AP2/FLASH function was significantly associated with altered transcription of the genes encoding the replication-dependent histone proteins as a result of the expression of the non-canonical polyA variants of these transcripts. Silencing of CASP8AP2/FLASH also mediated enrichment of changes in the expression of targets of the NF kappa B and MYC transcription factors. These findings were confirmed by whole transcriptome analysis of CASP8AP2/FLASH silenced cells at multiple time points. Finally, we identified and validated that CASP8AP2/FLASH LOF increases the expression of neurofilament heavy polypeptide (NEFH), a protein recently linked to regulation of the AKT1/beta-catenin pathway. Conclusions: We have used unbiased RNAi based approaches to identify and characterize the function of CASP8AP2/FLASH, a protein not previously reported as required for cell survival. This study further defines the role CASP8AP2/FLASH plays in the regulating expression of the replication-dependent histones and shows that its LOF results in broad and reproducible effects on the transcriptome of colorectal cancer cells including the induction of expression of the recently described tumor suppressor gene NEFH."],["dc.description.sponsorship","NIH, National Cancer Institute, Center for Cancer Research; NCI"],["dc.identifier.doi","10.1186/1476-4598-11-1"],["dc.identifier.isi","000301603300001"],["dc.identifier.pmid","22216762"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7195"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27412"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1476-4598"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Systems-wide RNAi analysis of CASP8AP2/FLASH shows transcriptional deregulation of the replication-dependent histone genes and extensive effects on the transcriptome of colorectal cancer cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]