Kramer, Frank

[["dc.bibliographiccitation.artnumber","1140"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","18"],["dc.contributor.affiliation","Jo, Peter; \t\t \r\n\t\t Department of General-, Visceral-, and Pediatric Surgery, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany, jo.peter@chirurgie-goettingen.de"],["dc.contributor.affiliation","Azizian, Azadeh; \t\t \r\n\t\t Department of General-, Visceral-, and Pediatric Surgery, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany, azadeh.azizian@med.uni-goettingen.de"],["dc.contributor.affiliation","Salendo, Junius; \t\t \r\n\t\t Department of General-, Visceral-, and Pediatric Surgery, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany, juniussalendo@gmail.com"],["dc.contributor.affiliation","Kramer, Frank; \t\t \r\n\t\t Department of Medical Statistics, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany, frank.kramer@med.uni-goettingen.de"],["dc.contributor.affiliation","Bernhardt, Markus; \t\t \r\n\t\t Department of General-, Visceral-, and Pediatric Surgery, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany, markus.bernhardt@med.uni-goettingen.de"],["dc.contributor.affiliation","Wolff, Hendrik; \t\t \r\n\t\t Department of Radiology, Nuclear Medicine and Radiotherapy, Radiology Munich, Burgstr. 7, 80333 Munich, Germany, drhawolff@googlemail.com"],["dc.contributor.affiliation","Gruber, Jens; \t\t \r\n\t\t German Primate Center, Medical RNA Biology, Kellnerweg 4, 37075 Goettingen, Germany, jgruber@dpz.eu"],["dc.contributor.affiliation","Grade, Marian; \t\t \r\n\t\t Department of General-, Visceral-, and Pediatric Surgery, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany, marian.grade@med.uni-goettingen.de"],["dc.contributor.affiliation","Beißbarth, Tim; \t\t \r\n\t\t Department of Medical Statistics, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany, tim.beissbarth@med.uni-goettingen.de"],["dc.contributor.affiliation","Ghadimi, B.; \t\t \r\n\t\t Department of General-, Visceral-, and Pediatric Surgery, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany, mghadim@uni-goettingen.de"],["dc.contributor.affiliation","Gaedcke, Jochen; \t\t \r\n\t\t Department of General-, Visceral-, and Pediatric Surgery, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany, jochen.gaedcke@med.uni-goettingen.de"],["dc.contributor.author","Jo, Peter"],["dc.contributor.author","Azizian, Azadeh"],["dc.contributor.author","Salendo, Junius"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Bernhardt, Markus"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Gruber, Jens"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Gaedcke, Jochen"],["dc.date.accessioned","2018-11-07T10:22:50Z"],["dc.date.available","2018-11-07T10:22:50Z"],["dc.date.issued","2017"],["dc.date.updated","2022-09-06T05:14:56Z"],["dc.description.abstract","Since the response to chemoradiotherapy in patients with locally advanced rectal cancer is heterogeneous, valid biomarkers are needed to monitor tumor response. Circulating microRNAs are promising candidates, however analyses of circulating microRNAs in rectal cancer are still rare. 111 patients with rectal cancer and 46 age-matched normal controls were enrolled. The expression levels of 30 microRNAs were analyzed in 17 pre-treatment patients' plasma samples. Differentially regulated microRNAs were validated in 94 independent patients. For 52 of the 94 patients a paired comparison between pre-treatment and post-treatment samples was performed. miR-17, miR-18b, miR-20a, miR-31, and miR-193a_3p, were significantly downregulated in pre-treatment plasma samples of patients with rectal cancer (p < 0.05). miR-29c, miR-30c, and miR-195 showed a trend of differential regulation. After validation, miR-31 and miR-30c were significantly deregulated by a decrease of expression. In 52 patients expression analyses of the 8 microRNAs in matched pre-treatment and post-treatment samples showed a significant decrease for all microRNAs (p < 0.05) after treatment. Expression levels of miR-31 and miR-30c could serve as valid biomarkers if validated in a prospective study. Plasma microRNA expression levels do not necessarily represent miRNA expression levels in tumor tissue. Also, expression levels of microRNAs change during multimodal therapy."],["dc.description.sponsorship","DFG (German Research Foundation)"],["dc.identifier.doi","10.3390/ijms18061140"],["dc.identifier.isi","000404581500040"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14793"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42349"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Mdpi Ag"],["dc.relation.eissn","1422-0067"],["dc.relation.issn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Changes of Microrna Levels in Plasma of Patients with Rectal Cancer during Chemoradiotherapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["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.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.artnumber","568"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Azizian, Azadeh"],["dc.contributor.author","Epping, Ingo"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Jo, Peter"],["dc.contributor.author","Bernhardt, Markus"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Salinas, Gabriela"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Beissbarath, Tim"],["dc.contributor.author","Ghadimi, B. Michael"],["dc.contributor.author","Gaedcke, Jochen"],["dc.date.accessioned","2018-11-07T10:16:01Z"],["dc.date.available","2018-11-07T10:16:01Z"],["dc.date.issued","2016"],["dc.description.abstract","Background: Patients with locally advanced rectal cancer are treated with preoperative chemoradiotherapy followed by surgical resection. Despite similar clinical parameters (uT2-3, uN+) and standard therapy, patients' prognoses differ widely. A possible prediction of prognosis through microRNAs as biomarkers out of treatment-naive biopsies would allow individualized therapy options. Methods: Microarray analysis of 45 microdissected preoperative biopsies from patients with rectal cancer was performed to identify potential microRNAs to predict overall survival, disease-free survival, cancer-specific survival, distant-metastasis-free survival, tumor regression grade, or nodal stage. Quantitative real-time polymerase chain reaction (qPCR) was performed on an independent set of 147 rectal cancer patients to validate relevant miRNAs. Results: In the microarray screen, 14 microRNAs were significantly correlated to overall survival. Five microRNAs were included from previous work. Finally, 19 miRNAs were evaluated by qPCR. miR-515-5p, miR-573, miR-579 and miR-802 demonstrated significant correlation with overall survival and cancer-specific survival (p<0.05). miR-573 was also significantly correlated with the tumor regression grade after preoperative chemoradiotherapy. miR-133b showed a significant correlation with distant-metastasis-free survival. miR-146b expression levels showed a significant correlation with nodal stage. Conclusion: Specific microRNAs can be used as biomarkers to predict prognosis of patients with rectal cancer and possibly stratify patients' therapy if validated in a prospective study."],["dc.identifier.doi","10.3390/ijms17040568"],["dc.identifier.isi","000374585300147"],["dc.identifier.pmid","27092493"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13222"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40949"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Mdpi Ag"],["dc.relation.issn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Prognostic Value of MicroRNAs in Preoperative Treated Rectal Cancer"],["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.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","2329"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","World Journal of Surgery"],["dc.bibliographiccitation.lastpage","2335"],["dc.bibliographiccitation.volume","39"],["dc.contributor.author","Azizian, Azadeh"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Jo, Peter"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Skarupke, Robert"],["dc.contributor.author","Bernhardt, Markus"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Gaedcke, Jochen"],["dc.date.accessioned","2018-11-07T09:52:56Z"],["dc.date.available","2018-11-07T09:52:56Z"],["dc.date.issued","2015"],["dc.description.abstract","In locally advanced rectal cancer, therapeutic success of preoperative chemoradiotherapy (CRT) ranges from resistance to complete regression. For those patients that respond well to CRT, local resection (LR) procedures are currently under investigation to minimize surgical morbidity and to improve functional outcome. To maintain the oncologic benefit appropriate staging procedures are essential. However, current clinical assessment and imaging techniques need further improvement. Five miRNAs associated with rectal cancer (miR-17, miR-18b, miR-20a, miR-31, and miR-193-3p) were analyzed in the plasma of rectal cancer patients (n = 42) using qPCR. Expression levels were assessed before, during and after CRT and analyzed in regard to patients' lymph node status obtained after total mesorectal excision and intensive histopathological work-up. Four of the five miRNAs revealed reliable results in the plasma. miR-31 was excluded due to its low expression. MicroRNA-17, 18b, 20a, and 193-3p showed altering expression levels at different time points. Only 43 % (miR-17), 43 % (miR-18b), 53 % (miR-20a), and 60 % (miR-193-3p) showed a continuous in- or decrease of miRNA expression. The reduced expression of miR-18b and miR-20a during CRT was found to be significantly associated with postoperative lymph node negativity (p < 0.05). MicroRNA expression in patient plasma changes during preoperative CRT. The alteration is not continuous and the meaning requires additional analysis on a larger patient cohort. The co-occurrence of reduced miR-18b and miR-20a expression with lymph node negativity after preoperative CRT could help to stratify the surgical procedure with respect to total mesorectal excision and LR if validated prospectively."],["dc.description.sponsorship","Clinical Research Unit [KFO 179]; Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.1007/s00268-015-3083-8"],["dc.identifier.isi","000359447800031"],["dc.identifier.pmid","25990502"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36226"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1432-2323"],["dc.relation.issn","0364-2313"],["dc.title","Preoperative Prediction of Lymph Node Status by Circulating Mir-18b and Mir-20a During Chemoradiotherapy in Patients with Rectal Cancer"],["dc.type","journal_article"],["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"]]

[["dc.bibliographiccitation.firstpage","1824"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Carcinogenesis"],["dc.bibliographiccitation.lastpage","1831"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Kendziorra, Emil"],["dc.contributor.author","Ahlborn, Kerstin"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Rave-Fränk, Margret"],["dc.contributor.author","Emons, Georg"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Ebner, Reinhard"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Ried, Thomas"],["dc.contributor.author","Grade, Marian"],["dc.date.accessioned","2018-11-07T08:49:29Z"],["dc.date.available","2018-11-07T08:49:29Z"],["dc.date.issued","2011"],["dc.description.abstract","A considerable percentage of rectal cancers are resistant to standard preoperative chemoradiotherapy. Because patients with a priori-resistant tumors do not benefit from multimodal treatment, understanding and overcoming this resistance remains of utmost clinical importance. We recently reported overexpression of the Wnt transcription factor TCF4, also known as TCF7L2, in rectal cancers that were resistant to 5-fluorouracil-based chemoradiotherapy. Because Wnt signaling has not been associated with treatment response, we aimed to investigate whether TCF4 mediates chemoradioresistance. RNA interference-mediated silencing of TCF4 was employed in three colorectal cancer (CRC) cell lines, and sensitivity to (chemo-) radiotherapy was assessed using a standard colony formation assay. Silencing of TCF4 caused a significant sensitization of CRC cells to clinically relevant doses of X-rays. This effect was restricted to tumor cells with high T cell factor (TCF) reporter activity, presumably in a beta-catenin-independent manner. Radiosensitization was the consequence of (i) a transcriptional deregulation of Wnt/TCF4 target genes, (ii) a silencing-induced G(2)/M phase arrest, (iii) an impaired ability to adequately halt cell cycle progression after radiation and (iv) a compromised DNA double strand break repair as assessed by gamma H2AX staining. Taken together, our results indicate a novel mechanism through which the Wnt transcription factor TCF4 mediates chemoradioresistance. Moreover, they suggest that TCF4 is a promising molecular target to sensitize resistant tumor cells to (chemo-) radiotherapy."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [KFO 179]"],["dc.identifier.doi","10.1093/carcin/bgr222"],["dc.identifier.isi","000297157700009"],["dc.identifier.pmid","21983179"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21469"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0143-3334"],["dc.title","Silencing of the Wnt transcription factor TCF4 sensitizes colorectal cancer cells to (chemo-) radiotherapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]