Rave-Fränk, Margret

[["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","621"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","The Oncologist"],["dc.bibliographiccitation.lastpage","631"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Conradi, Lena-Christin"],["dc.contributor.author","Schirmer, Markus Anton"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Sprenger, Thilo"],["dc.contributor.author","Rave-Fränk, Margret"],["dc.contributor.author","Hennies, Steffen"],["dc.contributor.author","Hess, Clemens Friedrich"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Liersch, Torsten"],["dc.date.accessioned","2018-11-07T09:01:50Z"],["dc.date.available","2018-11-07T09:01:50Z"],["dc.date.issued","2011"],["dc.description.abstract","Patients with locally advanced rectal cancer (cUICC stages II/III) are typically treated with preoperative 5-fluorouracil-based (5-FU-based) radiochemotherapy (RCT). However, trials are currently being conducted to improve the complete remission rates and the systemic control by combining 5-FU with oxaliplatin. The primary objective was to identify the subgroups of rectal cancer patients who were at risk for high-grade toxicity. All 196 patients who were included in the present study were treated with 50.4 Gy and chemotherapy that included either 5-FU (n = 115) or 5-FU + oxaliplatin (n + 81). The preoperative RCT was followed by a total mesorectal excision and adjuvant chemotherapy. Acute toxicity was monitored weekly and a toxicity grade >= 3 (Common Toxicity Criteria) for a skin reaction, cystitis, proctitis, or enteritis was defined as high-grade acute organ toxicity. After RCT with 5-FU + oxaliplatin, complete tumor remission was achieved in 13.6% of the patients and in 11.3% after RCT with 5-FU alone. Complete irradiation dosages of 50.4 Gy were given to 99% (5-FU) and 95% (5-FU + oxaliplatin) of the patients. Concomitant chemotherapy was fully administered in 95% of the patients treated with 5-FU compared with the 84% of patients treated with 5-FU + oxaliplatin. A significantly higher proportion of acute organ toxicity was found in the patients who were treated with 5-FU + oxaliplatin compared with those who were treated with 5-FU. Additionally, women with a low body mass index were at the highest risk for acute organ toxicity. These results suggest that there are basic clinical parameters, such as gender and body mass index, that may be potential markers for generating individual risk profiles of RCT-induced toxicity. The Oncologist 2011;16:621-631"],["dc.identifier.doi","10.1634/theoncologist.2010-0414"],["dc.identifier.isi","000290661900012"],["dc.identifier.pmid","21558132"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24528"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Alphamed Press"],["dc.relation.issn","1083-7159"],["dc.title","Gender-Specific Acute Organ Toxicity during Intensified Preoperative Radiochemotherapy for 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","285"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","International Journal of Radiation Biology"],["dc.bibliographiccitation.lastpage","298"],["dc.bibliographiccitation.volume","84"],["dc.contributor.author","Koenig, Sarah"],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Schmidt, Thordis-Karen"],["dc.contributor.author","Rave-Fraenk, Margret"],["dc.contributor.author","Rothe, Hilka"],["dc.contributor.author","Hermann, Robert Michael"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Hess, Clemens Friedrich"],["dc.contributor.author","Christiansen, Hans"],["dc.date.accessioned","2018-11-07T11:20:07Z"],["dc.date.available","2018-11-07T11:20:07Z"],["dc.date.issued","2008"],["dc.description.abstract","Purpose: Hepatocyte transplantation following liver irradiation (IR) and partial hepatectomy (PH) leads to extensive liver repopulation. We investigated the changes in the liver induced by IR explaining the loss of reproductive integrity in endogenous hepatocytes. Materials and methods: Right lobules of rat liver underwent external beam IR (25 Gy). A second group was subjected to additional 33% PH of the untreated left liver lobule. Liver specimens and controls were analyzed for DNA damage, apoptosis, proliferation and cell cycle related genes (1 hour to up to 12 weeks). Results: Double strand breaks (phosphorylated histone H2AX) induced by IR rapidly declined within hours and were no longer detectable after 4 days. No significant apoptosis was noted and steady mRNA levels (B-cell lymphoma 2-associated X protein (BAX), caspase 3 and 9) were in line with the lack of DNA fragmentation. However, gene expression of p53 and p21 in irradiated liver tissue increased. Transcripts of cyclin D1, proliferating cell nuclear antigen (PCNA), and cyclin B augmented progressively, whereas cyclin E was only affected moderately. Following PH, irradiated livers displayed persistently high protein levels of p21 and cyclin D1. However, cell divisions were infrequent, as reflected by low PCNA levels up to four weeks. Conclusion: IR leads to a major arrest in the G1/S phase and to a lesser extent in the G2/M transition of the cell cycle, resulting in reduced regenerative response following PH. The persistent block of at least four weeks may promote preferential proliferation of transplanted hepatocytes in this milieu."],["dc.identifier.doi","10.1080/09553000801953359"],["dc.identifier.isi","000254631200004"],["dc.identifier.pmid","18386194"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/55458"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Taylor & Francis Ltd"],["dc.relation.issn","1362-3095"],["dc.relation.issn","0955-3002"],["dc.title","Irradiation as preparative regimen for hepatocyte transplantation causes prolonged cell cycle block"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","149"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","International Journal of Radiation Oncology*Biology*Physics"],["dc.bibliographiccitation.lastpage","157"],["dc.bibliographiccitation.volume","83"],["dc.contributor.author","Schirmer, Markus Anton"],["dc.contributor.author","Mergler, Caroline Patricia Nadine"],["dc.contributor.author","Rave-Fränk, Margret"],["dc.contributor.author","Herrmann, Markus Karl Alfred"],["dc.contributor.author","Hennies, Steffen"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Conradi, Lena-Christin"],["dc.contributor.author","Jo, Peter"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Hess, Clemens Friedrich"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Brockmöller, Jürgen"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.date.accessioned","2018-11-07T09:10:56Z"],["dc.date.available","2018-11-07T09:10:56Z"],["dc.date.issued","2012"],["dc.description.abstract","Purpose: Transforming growth factor-beta1 is related to adverse events in radiochemotherapy. We investigated TGFB1 genetic variability in relation to quality of life-impairing acute organ toxicity (QAOT) of neoadjuvant radiochemotherapy under clinical trial conditions. Methods and Materials: Two independent patient cohorts (n = 88 and n = 75) diagnosed with International Union Against Cancer stage II/III rectal cancer received neoadjuvant radiation doses of 50.4 Gy combined with 5-fluorouracil-based chemotherapy. Toxicity was monitored according to Common Terminology Criteria for Adverse Events. QAOT was defined as a CTCAE grade >= 2 for at least one case of enteritis, proctitis, cystitis, or dermatitis. Nine germline polymorphisms covering the common genetic diversity in the TGFB1 gene were genotyped. Results: In both cohorts, all patients carrying the TGFB1 Pro25 variant experienced QAOT (positive predictive value of 100%, adjusted p = 0.0006). In a multivariate logistic regression model, gender, age, body mass index, type of chemotherapy, or disease state had no significant impact on QAOT. Conclusion: The TGFB1 Pro25 variant could be a relevant marker for individual treatment stratification and carriers may benefit from adaptive clinical care or specific radiation techniques. (C) 2012 Elsevier Inc."],["dc.description.sponsorship","German Research Foundation (DFG) [KFO 179]"],["dc.identifier.doi","10.1016/j.ijrobp.2011.05.063"],["dc.identifier.isi","000302993900044"],["dc.identifier.pmid","22000747"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26603"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","0360-3016"],["dc.title","Acute Toxicity of Radiochemotherapy in Rectal Cancer Patients: A Risk Particularly for Carriers of the TGFB1 Pro25 variant"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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","3928"],["dc.bibliographiccitation.issue","31"],["dc.bibliographiccitation.journal","World journal of gastroenterology : WJG"],["dc.bibliographiccitation.lastpage","3935"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Rave-Fränk, Margret"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Koenig, Sarah"],["dc.date.accessioned","2019-07-10T08:13:36Z"],["dc.date.available","2019-07-10T08:13:36Z"],["dc.date.issued","2010"],["dc.description.abstract","AIM: To investigate whether irradiation (IR) and partial hepatectomy (PH) may prepare the host liver for non-parenchymal cell (NPC) transplantation. METHODS: Livers of dipeptidyl peptidase IV (DPPIV)-deficient rats were pre-conditioned with external beam IR (25 Gy) delivered to two-thirds of the right liver lobules followed by a one-third PH of the untreated lobule. DPPIV-positive liver cells (NPC preparations enriched for liver sinusoidal endothelial cells (LSECs) and hepatocytes) were transplanted via the spleen into the recipient livers. The extent and quality of donor cell engraftment and growth was studied over a long-term interval of 16 wk after transplantation. RESULTS: Host liver staining demonstrated 3 different repopulation types. Well defined clusters of donor-derived hepatocytes with canalicular expression of DPPIV were detectable either adjacent to or in between large areas of donor cells (covering up to 90% of the section plane) co-expressing the endothelial marker platelet endothelial cell adhesion molecule. The third type consisted of formations of DPPIV-positive duct-like structures which co-localized with biliary epithelial CD49f. CONCLUSION: Liver IR and PH as a preconditioning stimulus enables multiple cell liver repopulation by donor hepatocytes, LSECs, and bile duct cells."],["dc.identifier.fs","574471"],["dc.identifier.pmid","20712054"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6866"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61286"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1007-9327"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Bile Ducts"],["dc.subject.mesh","Cell Proliferation"],["dc.subject.mesh","Cell Survival"],["dc.subject.mesh","Dipeptidyl Peptidase 4"],["dc.subject.mesh","Endothelial Cells"],["dc.subject.mesh","Hepatectomy"],["dc.subject.mesh","Hepatocytes"],["dc.subject.mesh","Liver"],["dc.subject.mesh","Liver Regeneration"],["dc.subject.mesh","Rats"],["dc.subject.mesh","Rats, Inbred F344"],["dc.subject.mesh","Rats, Transgenic"],["dc.subject.mesh","Time Factors"],["dc.subject.mesh","Transplantation Conditioning"],["dc.title","Liver sinusoidal endothelial and biliary cell repopulation following irradiation and partial hepatectomy."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1214"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","International Journal of Radiation Oncology*Biology*Physics"],["dc.bibliographiccitation.lastpage","1219"],["dc.bibliographiccitation.volume","80"],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Rave-Frank, Margret"],["dc.contributor.author","Schmidberger, Heinz"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Hess, Clemens Friedrich"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Koenig, Sarah"],["dc.date.accessioned","2018-11-07T08:54:18Z"],["dc.date.available","2018-11-07T08:54:18Z"],["dc.date.issued","2011"],["dc.description.abstract","Purpose: Hepatocyte transplantation is strongly considered to be a promising option to correct chronic liver failure through repopulation of the diseased organ. We already reported on extensive liver repopulation by hepatocytes transplanted into rats preconditioned with 25-Gy single dose selective external beam irradiation (IR). Herein, we tested lower radiation doses and fractionated protocols, which would be applicable in clinical use. Methods and Material: Livers of dipeptidylpeptidase IV (DPPIV)-deficient rats were preconditioned with partial liver external beam single dose IR at 25 Gy, 8 Gy, or 5 Gy, or fractionated IR at 5 x 5 Gy or 5 x 2 Gy. Four days after completion of IR, a partial hepatectomy (PH) was performed to resect the untreated liver section. Subsequently, 12 million wild-type (DPPIV(+)) hepatocytes were transplanted via the spleen into the recipient livers. The degree of donor cell integration and liver repopulation was studied 16 weeks after transplantation by means of immunofluorescence and DPPIV-luminescence assay. Results: Donor hepatocyte integration and liver repopulation were more effective in the irradiated livers following pretreatment with the IR doses 1 x 25 Gy and 5 x 5 Gy (formation of large DPPIV-positive cell clusters) than single-dose irradiation at 8 Gy or 5 Gy (DPPIV-positive clusters noticeably smaller and less frequent). Quantitative analysis of extracted DPPIV revealed signals exceeding the control level in all transplanted animals treated with IR and PH. Compared with the standard treatment of 1 x 25 Gy, fractionation with 5 x 5 Gy was equally efficacious, the Mann-Whitney U test disclosing no statistically significant difference (p = 0.146). The lower doses of 1 x 5 Gy, 1 x 8 Gy, and 5 x 2 Gy were significantly less effective with p < 0.05. Conclusion: This study suggests that fractionated radiotherapy in combination with PH is a conceivable pretreatment approach to prime the host liver for hepatocyte transplantation, thus bringing the experimental model a step closer to clinical application. (C) 2011 Elsevier Inc."],["dc.identifier.doi","10.1016/j.ijrobp.2011.02.035"],["dc.identifier.isi","000292486200035"],["dc.identifier.pmid","21514075"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22639"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","0360-3016"],["dc.title","FRACTIONATED EXTERNAL BEAM RADIOTHERAPY AS A SUITABLE PREPARATIVE REGIMEN FOR HEPATOCYTE TRANSPLANTATION AFTER PARTIAL HEPATECTOMY"],["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"]]