Gaedcke, Jochen

[["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.artnumber","7677"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Russell, Ronan"],["dc.contributor.author","Perkhofer, Lukas"],["dc.contributor.author","Liebau, Stefan"],["dc.contributor.author","Lin, Qiong"],["dc.contributor.author","Lechel, Andre"],["dc.contributor.author","Feld, Fenja M."],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Guethle, Melanie"],["dc.contributor.author","Zenke, Martin"],["dc.contributor.author","Hartmann, Daniel"],["dc.contributor.author","von Figura, Guido"],["dc.contributor.author","Weissinger, Stephanie E."],["dc.contributor.author","Rudolph, K. Lenhard"],["dc.contributor.author","Moeller, Peter"],["dc.contributor.author","Lennerz, Jochen K."],["dc.contributor.author","Seufferlein, Thomas"],["dc.contributor.author","Wagner, Martin"],["dc.contributor.author","Kleger, Alexander"],["dc.date.accessioned","2018-11-07T09:54:59Z"],["dc.date.available","2018-11-07T09:54:59Z"],["dc.date.issued","2015"],["dc.description.abstract","Pancreatic ductal adenocarcinoma (PDAC) is associated with accumulation of particular oncogenic mutations and recent genetic sequencing studies have identified ataxia telangiectasia-mutated (ATM) mutations in PDAC cohorts. Here we report that conditional deletion of ATM in a mouse model of PDAC induces a greater number of proliferative precursor lesions coupled with a pronounced fibrotic reaction. ATM-targeted mice display altered TGF beta-superfamily signalling and enhanced epithelial-to-mesenchymal transition (EMT) coupled with shortened survival. Notably, our mouse model recapitulates many features of more aggressive human PDAC subtypes. Particularly, we report that low expression of ATM predicts EMT, a gene signature specific for Bmp4 signalling and poor prognosis in human PDAC. Our data suggest an intimate link between ATM expression and pancreatic cancer progression in mice and men."],["dc.identifier.doi","10.1038/ncomms8677"],["dc.identifier.isi","000358858100021"],["dc.identifier.pmid","26220524"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12073"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36658"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2041-1723"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Loss of ATM accelerates pancreatic cancer formation and epithelial-mesenchymal transition"],["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","837"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Gastrointestinal Surgery"],["dc.bibliographiccitation.lastpage","839"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Schueler, Philipp"],["dc.contributor.author","Brinker, J."],["dc.contributor.author","Quintel, M."],["dc.contributor.author","Ghadimi, Michael B."],["dc.date.accessioned","2018-11-07T09:26:42Z"],["dc.date.available","2018-11-07T09:26:42Z"],["dc.date.issued","2013"],["dc.description.abstract","Giant inguinoscrotal hernias are rare but still exist even in developed countries. Although accompanied by a higher perioperative mortality, an elective surgical approach should be undertaken. In critically ill patients, however, the surgical intervention requires specific demands. We report a case of a 45-year-old man who was referred to the hospital after perforation of the hernia with concomitant peritonitis and sepsis. After initial stabilization of the patient, a subtotal colectomy and a partial small bowl resection was performed. In a second step after stabilization of organ functions, the hernia sac was resected, and the abdominal cavity was reconstructed. The patient was discharged and is doing well until today but still refuses any plastic surgery. Resection of giant inguinoscrotal hernia is feasible even in patients being administered in an emergency setting. Especially in case of an intra-abdominal infection, intestinal resection is the therapy of choice to allow the reconstruction of the abdominal cavity. A two-step approach should be considered to allow a successful recovery."],["dc.identifier.doi","10.1007/s11605-012-2136-7"],["dc.identifier.isi","000316335000032"],["dc.identifier.pmid","23299222"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10384"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30359"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1091-255X"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Emergency Repair of Giant Inguinoscrotal Hernia in a Septic Patient"],["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","2828"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Cancers"],["dc.bibliographiccitation.volume","14"],["dc.contributor.affiliation","Bremer, Sebastian C. B.; 1Clinic for Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; alexander.koenig@med.uni-goettingen.de (A.O.K.); ahmad.amanzada@med.uni-goettingen.de (A.A.); volker.ellenrieder@med.uni-goettingen.de (V.E.)"],["dc.contributor.affiliation","Bittner, Gabi; 2Institute of Pathology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; bittnergabi@outlook.de (G.B.); omar.elakad@med.uni-goettingen.de (O.E.); dinterhelen@gmail.com (H.D.); philipp.stroebel@med.uni-goettingen.de (P.S.); hanibal.bohnenberger@med.uni-goettingen.de (H.B.)"],["dc.contributor.affiliation","Elakad, Omar; 2Institute of Pathology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; bittnergabi@outlook.de (G.B.); omar.elakad@med.uni-goettingen.de (O.E.); dinterhelen@gmail.com (H.D.); philipp.stroebel@med.uni-goettingen.de (P.S.); hanibal.bohnenberger@med.uni-goettingen.de (H.B.)"],["dc.contributor.affiliation","Dinter, Helen; 2Institute of Pathology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; bittnergabi@outlook.de (G.B.); omar.elakad@med.uni-goettingen.de (O.E.); dinterhelen@gmail.com (H.D.); philipp.stroebel@med.uni-goettingen.de (P.S.); hanibal.bohnenberger@med.uni-goettingen.de (H.B.)"],["dc.contributor.affiliation","Gaedcke, Jochen; 3Clinic for General, Visceral and Pediatric Surgery, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; jochen.gaedcke@med.uni-goettingen.de"],["dc.contributor.affiliation","König, Alexander O.; 1Clinic for Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; alexander.koenig@med.uni-goettingen.de (A.O.K.); ahmad.amanzada@med.uni-goettingen.de (A.A.); volker.ellenrieder@med.uni-goettingen.de (V.E.)"],["dc.contributor.affiliation","Amanzada, Ahmad; 1Clinic for Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; alexander.koenig@med.uni-goettingen.de (A.O.K.); ahmad.amanzada@med.uni-goettingen.de (A.A.); volker.ellenrieder@med.uni-goettingen.de (V.E.)"],["dc.contributor.affiliation","Ellenrieder, Volker; 1Clinic for Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; alexander.koenig@med.uni-goettingen.de (A.O.K.); ahmad.amanzada@med.uni-goettingen.de (A.A.); volker.ellenrieder@med.uni-goettingen.de (V.E.)"],["dc.contributor.affiliation","Freiherr von Hammerstein-Equord, Alexander; 4Clinic for Cardiac, Thoracic and Vascular Surgery, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; alexander.hammerstein@med.uni-goettingen.de"],["dc.contributor.affiliation","Ströbel, Philipp; 2Institute of Pathology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; bittnergabi@outlook.de (G.B.); omar.elakad@med.uni-goettingen.de (O.E.); dinterhelen@gmail.com (H.D.); philipp.stroebel@med.uni-goettingen.de (P.S.); hanibal.bohnenberger@med.uni-goettingen.de (H.B.)"],["dc.contributor.affiliation","Bohnenberger, Hanibal; 2Institute of Pathology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, Germany; bittnergabi@outlook.de (G.B.); omar.elakad@med.uni-goettingen.de (O.E.); dinterhelen@gmail.com (H.D.); philipp.stroebel@med.uni-goettingen.de (P.S.); hanibal.bohnenberger@med.uni-goettingen.de (H.B.)"],["dc.contributor.author","Bremer, Sebastian C. B."],["dc.contributor.author","Bittner, Gabi"],["dc.contributor.author","Elakad, Omar"],["dc.contributor.author","Dinter, Helen"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","König, Alexander O."],["dc.contributor.author","Amanzada, Ahmad"],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Freiherr von Hammerstein-Equord, Alexander"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.date.accessioned","2022-07-01T07:35:31Z"],["dc.date.available","2022-07-01T07:35:31Z"],["dc.date.issued","2022"],["dc.date.updated","2022-07-08T10:03:36Z"],["dc.description.abstract","Tumor grading is a robust prognostic predictor in patients with neuroendocrine neoplasms (NEN) and guides therapy, especially in tumors with high proliferation. NEN can be separated into well-differentiated and poorly differentiated types. The more aggressive NEN have been further separated into neuroendocrine tumors (NET G3) with a better prognosis and neuroendocrine carcinomas (NEC) with a worse prognosis. Despite this distinction’s tremendous clinical and therapeutic relevance, optimal diagnostic biomarkers are still lacking. In this study, we analyzed the protein expression and prognostic impact of Enhancer of Zeste Homolog 2 (EZH2) by immunohistochemistry in 219 tissue samples of gastroenteropancreatic (GEP-NEN) and pulmonary NEN (P-NEN). EZH2 was almost exclusively expressed in NEN with a proliferation rate above 20% (G3), while all low-grade tumors were nearly negative. Among high-grade NEN, 65% showed high and 35% low expression of EZH2. In this group, the high expression of EZH2 was significantly associated with poor overall survival and NEC histology. Interestingly, EZH2 seems to act independently of Polycomb Repressive Complex 2 (PRC2) in NEN. In conclusion, we propose EZH2 as a robust biomarker for distinguishing between NET G3 and NEC among gastroenteropancreatic and pulmonary NEN."],["dc.description.sponsorship","Deutsche Krebshilfe"],["dc.description.sponsorship","University Medical Center Göttingen"],["dc.description.sponsorship","Else-Kröner-Fresenius-Stiftung"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.3390/cancers14122828"],["dc.identifier.pii","cancers14122828"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112190"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112412"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-581"],["dc.relation.eissn","2072-6694"],["dc.rights","CC BY 4.0"],["dc.title","Enhancer of Zeste Homolog 2 (EZH2) Is a Marker of High-Grade Neuroendocrine Neoplasia in Gastroenteropancreatic and Pulmonary Tract and Predicts Poor Prognosis"],["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","e1005675"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","PLoS Genetics"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Wu, Y."],["dc.contributor.author","Lee, Suk-Hee"],["dc.contributor.author","Williamson, Elizabeth A."],["dc.contributor.author","Reinert, Brian L."],["dc.contributor.author","Cho, Ju Hwan"],["dc.contributor.author","Xia, Fen"],["dc.contributor.author","Jaiswal, Aruna Shanker"],["dc.contributor.author","Srinivasan, Gayathri"],["dc.contributor.author","Patel, Bhavita"],["dc.contributor.author","Brantley, Alexis"],["dc.contributor.author","Zhou, D."],["dc.contributor.author","Shao, Lijian"],["dc.contributor.author","Pathak, Rupak"],["dc.contributor.author","Hauer-Jensen, Martin"],["dc.contributor.author","Singh, Sudha"],["dc.contributor.author","Kong, Kimi"],["dc.contributor.author","Wu, X."],["dc.contributor.author","Kim, Hyun-Suk"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Burma, Sandeep"],["dc.contributor.author","Nickoloff, Jac A."],["dc.contributor.author","Hromas, Robert A."],["dc.date.accessioned","2018-11-07T09:47:57Z"],["dc.date.available","2018-11-07T09:47:57Z"],["dc.date.issued","2015"],["dc.description.abstract","Replication fork stalling and collapse is a major source of genome instability leading to neoplastic transformation or cell death. Such stressed replication forks can be conservatively repaired and restarted using homologous recombination (HR) or non-conservatively repaired using micro-homology mediated end joining (MMEJ). HR repair of stressed forks is initiated by 5' end resection near the fork junction, which permits 3' single strand invasion of a homologous template for fork restart. This 5' end resection also prevents classical non-homologous end-joining (cNHEJ), a competing pathway for DNA double-strand break (DSB) repair. Unopposed NHEJ can cause genome instability during replication stress by abnormally fusing free double strand ends that occur as unstable replication fork repair intermediates. We show here that the previously uncharacterized Exonuclease/Endonuclease/Phosphatase Domain-1 (EEPD1) protein is required for initiating repair and restart of stalled forks. EEPD1 is recruited to stalled forks, enhances 5' DNA end resection, and promotes restart of stalled forks. Interestingly, EEPD1 directs DSB repair away from cNHEJ, and also away from MMEJ, which requires limited end resection for initiation. EEPD1 is also required for proper ATR and CHK1 phosphorylation, and formation of gamma-H2AX, RAD51 and phospho-RPA32 foci. Consistent with a direct role in stalled replication fork cleavage, EEPD1 is a 5' overhang nuclease in an obligate complex with the end resection nuclease Exo1 and BLM. EEPD1 depletion causes nuclear and cytogenetic defects, which are made worse by replication stress. Depleting 53BP1, which slows cNHEJ, fully rescues the nuclear and cytogenetic abnormalities seen with EEPD1 depletion. These data demonstrate that genome stability during replication stress is maintained by EEPD1, which initiates HR and inhibits cNHEJ and MMEJ."],["dc.identifier.doi","10.1371/journal.pgen.1005675"],["dc.identifier.isi","000368518400016"],["dc.identifier.pmid","26684013"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12699"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35210"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1553-7404"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","EEPD1 Rescues Stressed Replication Forks and Maintains Genome Stability by Promoting End Resection and Homologous Recombination Repair"],["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.artnumber","e1411"],["dc.bibliographiccitation.journal","Cell Death and Disease"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Landmann, H."],["dc.contributor.author","Proia, D. A."],["dc.contributor.author","He, S."],["dc.contributor.author","Ogden, F. L."],["dc.contributor.author","Kramer, Franz-Josef"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Moll, U."],["dc.contributor.author","Dobbelstein, Matthias"],["dc.date.accessioned","2018-11-07T09:35:41Z"],["dc.date.available","2018-11-07T09:35:41Z"],["dc.date.issued","2014"],["dc.description.abstract","HSP90 inhibition represents a promising route to cancer therapy, taking advantage of cancer cell-inherent proteotoxic stress. The HSP90-inhibitor ganetespib showed benefit in advanced clinical trials. This raises the need to identify the molecular determinants of treatment response. We tested the efficacy of ganetespib on a series of colorectal cancer (CRC)-derived cell lines and correlated their sensitivities with comprehensive gene expression analysis. Notably, the drug concentration required for 50% growth inhibition (IC50) varied up to 70-fold (from 36 to 2500 nM) between different cell lines. Correlating cell line-specific IC(50)s with the corresponding gene expression patterns revealed a strong association between ganetespib resistance (IC50 > 500 nM) and high expression of the UDP glucuronosyltransferase 1A (UGT1A) gene cluster. Moreover, CRC tumor samples showed a comparable distribution of UGT1A expression levels. The members of the UGT1A gene family are known as drug-conjugating liver enzymes involved in drug excretion, but their function in tumor cells is hardly understood. Chemically unrelated HSP90 inhibitors, for example, 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), did not show correlation of drug sensitivities with UGT1A levels, whereas the ganetespib-related compound NVP-AUY922 did. When the most ganetespib-resistant cell line, HT29, was treated with ganetespib, the levels of HSP90 clients were unaffected. However, HT29 cells became sensitized to the drug, and HSP90 client proteins were destabilized by ganetespib upon siRNA-mediated UGT1A knockdown. Conversely, the most ganetespib-sensitive cell lines HCT116 and SW480 became more tolerant toward ganetespib upon UGT1A overexpression. Mechanistically, ganetespib was rapidly glucuronidated and excreted in resistant but not in sensitive CRC lines. We conclude that CRC cell-expressed UGT1A inactivates ganetespib and other resorcinolic Hsp90 inhibitors by glucuronidation, which renders the drugs unable to inhibit Hsp90 and thereby abrogates their biological activity. UGT1A levels in tumor tissues may be a suitable predictive biomarker to stratify CRC patients for ganetespib treatment."],["dc.description.sponsorship","Open-Access Publikationsfonds 2014"],["dc.identifier.doi","10.1038/cddis.2014.378"],["dc.identifier.isi","000343162000012"],["dc.identifier.pmid","25210794"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10891"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32445"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","Najko"],["dc.relation.issn","2041-4889"],["dc.rights","CC BY-NC-ND 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/3.0"],["dc.title","UDP glucuronosyltransferase 1A expression levels determine the response of colorectal cancer cells to the heat shock protein 90 inhibitor ganetespib"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2805"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Cancers"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Leu, Martin"],["dc.contributor.author","Riebeling, Theresa"],["dc.contributor.author","Dröge, Leif Hendrik"],["dc.contributor.author","Hubert, Laura"],["dc.contributor.author","Guhlich, Manuel"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Brockmöller, Jürgen"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Rieken, Stefan"],["dc.contributor.author","Schirmer, Markus Anton"],["dc.date.accessioned","2021-07-05T15:00:42Z"],["dc.date.available","2021-07-05T15:00:42Z"],["dc.date.issued","2021"],["dc.description.abstract","Despite excellent loco-regional control by multimodal treatment of locally advanced rectal cancer, a substantial portion of patients succumb to this disease. As many treatment effects are mediated via reactive oxygen species (ROS), we evaluated the effect of single nucleotide polymorphisms (SNPs) in ROS-related genes on clinical outcome. Based on the literature, eight SNPs in seven ROS-related genes were assayed. Eligible patients (n = 287) diagnosed with UICC stage II/III rectal cancer were treated multimodally starting with neoadjuvant radiochemotherapy (N-RCT) according to the clinical trial protocols of CAO/ARO/AIO-94, CAO/ARO/AIO-04, TransValid-A, and TransValid-B. The median follow-up was 64.4 months. The Ser326Cys polymorphism in the human OGG1 gene affected clinical outcome, in particular cancer-specific survival (CSS). This effect was comparable in extent to the ypN status, an already established strong prognosticator for patient outcome. Homozygous and heterozygous carriers of the Cys326 variant (n = 105) encountered a significantly worse CSS (p = 0.0004 according to the log-rank test, p = 0.01 upon multiple testing adjustment). Cox regression elicited a hazard ratio for CSS of 3.64 (95% confidence interval 1.70–7.78) for patients harboring the Cys326 allele. In a multivariable analysis, the effect of Cys326 on CSS was preserved. We propose the genetic polymorphism Ser326Cys as a promising biomarker for outcome in rectal cancer."],["dc.description.abstract","Despite excellent loco-regional control by multimodal treatment of locally advanced rectal cancer, a substantial portion of patients succumb to this disease. As many treatment effects are mediated via reactive oxygen species (ROS), we evaluated the effect of single nucleotide polymorphisms (SNPs) in ROS-related genes on clinical outcome. Based on the literature, eight SNPs in seven ROS-related genes were assayed. Eligible patients (n = 287) diagnosed with UICC stage II/III rectal cancer were treated multimodally starting with neoadjuvant radiochemotherapy (N-RCT) according to the clinical trial protocols of CAO/ARO/AIO-94, CAO/ARO/AIO-04, TransValid-A, and TransValid-B. The median follow-up was 64.4 months. The Ser326Cys polymorphism in the human OGG1 gene affected clinical outcome, in particular cancer-specific survival (CSS). This effect was comparable in extent to the ypN status, an already established strong prognosticator for patient outcome. Homozygous and heterozygous carriers of the Cys326 variant (n = 105) encountered a significantly worse CSS (p = 0.0004 according to the log-rank test, p = 0.01 upon multiple testing adjustment). Cox regression elicited a hazard ratio for CSS of 3.64 (95% confidence interval 1.70–7.78) for patients harboring the Cys326 allele. In a multivariable analysis, the effect of Cys326 on CSS was preserved. We propose the genetic polymorphism Ser326Cys as a promising biomarker for outcome in rectal cancer."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.3390/cancers13112805"],["dc.identifier.pii","cancers13112805"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87886"],["dc.language.iso","en"],["dc.notes.intern","DOI Import DOI-Import GROB-441"],["dc.publisher","MDPI"],["dc.relation.eissn","2072-6694"],["dc.rights","https://creativecommons.org/licenses/by/4.0/"],["dc.title","8-Oxoguanine DNA Glycosylase (OGG1) Cys326 Variant: Increased Risk for Worse Outcome of Patients with Locally Advanced Rectal Cancer after Multimodal Therapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","227"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Digestion"],["dc.bibliographiccitation.lastpage","235"],["dc.bibliographiccitation.volume","102"],["dc.contributor.affiliation","Bremer, Sebastian C.B.; \r\n aClinic for Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany"],["dc.contributor.affiliation","Conradi, Lena-Christin; \r\n bClinic for General, Visceral and Pediatric Surgery, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany"],["dc.contributor.affiliation","Mechie, Nicolae-Catalin; \r\n aClinic for Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany"],["dc.contributor.affiliation","Amanzada, Ahmad; \r\n aClinic for Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany"],["dc.contributor.affiliation","Mavropoulou, Eirini; \r\n aClinic for Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany"],["dc.contributor.affiliation","Kitz, Julia; \r\n cInstitute of Pathology, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany"],["dc.contributor.affiliation","Ghadimi, Michael; \r\n bClinic for General, Visceral and Pediatric Surgery, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany"],["dc.contributor.affiliation","Ellenrieder, Volker; \r\n aClinic for Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany"],["dc.contributor.affiliation","Ströbel, Philipp; \r\n cInstitute of Pathology, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany"],["dc.contributor.affiliation","Hessmann, Elisabeth; \r\n aClinic for Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany"],["dc.contributor.affiliation","Gaedcke, Jochen; \r\n bClinic for General, Visceral and Pediatric Surgery, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany"],["dc.contributor.affiliation","Bohnenberger, Hanibal; \r\n cInstitute of Pathology, University Medical Center Goettingen, Georg-August-University, Goettingen, Germany"],["dc.contributor.author","Bremer, Sebastian C. B."],["dc.contributor.author","Mechie, Nicolae-Catalin"],["dc.contributor.author","Mavropoulou, Eirini"],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Conradi, Lena-Christin"],["dc.contributor.author","Amanzada, Ahmad"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Ghadimi, Michael"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.date.accessioned","2021-04-26T11:54:07Z"],["dc.date.available","2021-04-26T11:54:07Z"],["dc.date.issued","2021"],["dc.date.updated","2022-03-21T21:17:53Z"],["dc.description.abstract","Colorectal cancer (CRC) is the leading gastrointestinal malignancy. The development from premalignant intraepithelial lesions leading to invasive cancer is paradigmatic for the stepwise carcinogenesis of epithelial cancers, but the knowledge of the underlying mechanism of carcinogenesis and progression of CRC is still incomplete. The understanding of epigenetic mechanisms of carcinogenesis has led to new therapeutic approaches during the last years. Enhancer of zeste homolog 2 (EZH2) is one central epigenetic silencer of the polycomb repressor complex 2 (PRC2) that is already in clinical use as a novel drug target and is associated with poorer prognosis in several cancer entities."],["dc.identifier","31694013"],["dc.identifier.doi","10.1159/000504093"],["dc.identifier.pmid","31694013"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/84358"],["dc.language.iso","en"],["dc.publisher","S. Karger AG"],["dc.relation.eissn","1421-9867"],["dc.relation.issn","0012-2823"],["dc.relation.issn","1421-9867"],["dc.rights.uri","https://www.karger.com/Services/SiteLicenses"],["dc.title","Enhancer of Zeste Homolog 2 in Colorectal Cancer Development and Progression"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","721"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Clinical Chemistry and Laboratory Medicine (CCLM)"],["dc.bibliographiccitation.lastpage","725"],["dc.bibliographiccitation.volume","50"],["dc.contributor.author","Sharon, Elad"],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Hollevoet, Kevin"],["dc.contributor.author","Steinberg, Seth M."],["dc.contributor.author","Pastan, Ira"],["dc.contributor.author","Onda, Masanori"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Ghadimi, B. Michael"],["dc.contributor.author","Ried, Thomas"],["dc.contributor.author","Hassan, Raffit"],["dc.date.accessioned","2018-11-07T09:14:30Z"],["dc.date.available","2018-11-07T09:14:30Z"],["dc.date.issued","2012"],["dc.description.abstract","Background: Tumor mesothelin overexpression is present in different malignancies, including the majority of patients with pancreatic or biliary cancers. The objective of this study was to evaluate the use of shed serum mesothelin and megakaryocyte potentiating factor (MPF) concentrations as biomarkers for these cancers. Methods: A total of 151 individuals, divided into five groups, were retrospectively analyzed: healthy donors (n=15), patients with benign non-pancreatic conditions (n=52), benign pancreatic conditions (n=33), biliary carcinoma (n=9), and pancreatic ductal adenocarcinoma (n=42). Mesothelin and MPF concentrations were measured in serum with the Mesomark (TM) and Human MPF ELISA, respectively. Results: Mesothelin and MPF concentrations did not significantly differ among the five individual participant groups (p=0.34, p=0.33, respectively), nor did any other combination and pair-wise comparison of the participant groups demonstrated a significant difference in biomarker concentrations. In patients with pancreatic cancer, mesothelin or MPF concentrations were not associated with tumor stage (p=0.87, p=0.48, respectively) or differentiation grade (p=0.73, p=0.52, respectively). Conclusions: Serum mesothelin and MPF concentrations, measured with standard available ELISAs, were not specific for benign or pancreatic disease. Both biomarkers were not elevated in patients with pancreatic or biliary cancers, and consequently do not appear to be useful biomarkers for these malignancies."],["dc.description.sponsorship","NIH, National Cancer Institute, Center for Cancer Research"],["dc.identifier.doi","10.1515/CCLM.2011.816"],["dc.identifier.isi","000304337100020"],["dc.identifier.pmid","22149739"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10596"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27424"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Walter De Gruyter Gmbh"],["dc.relation.issn","1434-6621"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Serum mesothelin and megakaryocyte potentiating factor in pancreatic and biliary cancers"],["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","7635"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","7650"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Hara, Toshifumi"],["dc.contributor.author","Jones, Matthew F."],["dc.contributor.author","Subramanian, Murugan"],["dc.contributor.author","Li, Xiao Ling"],["dc.contributor.author","Ou, Oliver"],["dc.contributor.author","Zhu, Yuelin"],["dc.contributor.author","Yang, Yuan"],["dc.contributor.author","Wakefield, Lalage M."],["dc.contributor.author","Hussain, S. Perwez"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Ried, Thomas"],["dc.contributor.author","Luo, Ji"],["dc.contributor.author","Caplen, Natasha J."],["dc.contributor.author","Lal, Ashish"],["dc.date.accessioned","2019-07-10T08:11:55Z"],["dc.date.available","2019-07-10T08:11:55Z"],["dc.date.issued","2014-09-15"],["dc.description.abstract","MicroRNAs (miRNAs) regulate the expression of hundreds of genes. However, identifying the critical targets within a miRNA-regulated gene network is challenging. One approach is to identify miRNAs that exert a context-dependent effect, followed by expression profiling to determine how specific targets contribute to this selective effect. In this study, we performed miRNA mimic screens in isogenic KRAS-Wild-type (WT) and KRAS-Mutant colorectal cancer (CRC) cell lines to identify miRNAs selectively targeting KRAS-Mutant cells. One of the miRNAs we identified as a selective inhibitor of the survival of multiple KRAS-Mutant CRC lines was miR-126. In KRAS-Mutant cells, miR-126 over-expression increased the G1 compartment, inhibited clonogenicity and tumorigenicity, while exerting no effect on KRAS-WT cells. Unexpectedly, the miR-126-regulated transcriptome of KRAS-WT and KRAS-Mutant cells showed no significant differences. However, by analyzing the overlap between miR-126 targets with the synthetic lethal genes identified by RNAi in KRAS-Mutant cells, we identified and validated a subset of miR-126-regulated genes selectively required for the survival and clonogenicity of KRAS-Mutant cells. Our strategy therefore identified critical target genes within the miR-126-regulated gene network. We propose that the selective effect of miR-126 on KRAS-Mutant cells could be utilized for the development of targeted therapy for KRAS mutant tumors."],["dc.identifier.fs","612070"],["dc.identifier.pmid","25245095"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11992"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60820"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1949-2553"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Selective targeting of KRAS-mutant cells by miR-126 through repression of multiple genes essential for the survival of KRAS-mutant cells."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]