Ghadimi, Michael B.

[["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.firstpage","591"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Langenbeck s Archives of Surgery"],["dc.bibliographiccitation.lastpage","606"],["dc.bibliographiccitation.volume","396"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Quintel, Michael"],["dc.contributor.author","Ghadimi, B. Michael"],["dc.date.accessioned","2018-11-07T08:55:38Z"],["dc.date.available","2018-11-07T08:55:38Z"],["dc.date.issued","2011"],["dc.description.abstract","The outcome of patients who are scheduled for gastrointestinal surgery is influenced by various factors, the most important being the age and comorbidities of the patient, the complexity of the surgical procedure and the management of postoperative recovery. To improve patient outcome, close cooperation between surgeons and anaesthesiologists (joint risk assessment) is critical. This cooperation has become increasingly important because more and more patients are being referred to surgery at an advanced age and with multiple comorbidities and because surgical procedures and multimodal treatment modalities are becoming more and more complex. The aim of this review is to provide clinicians with practical recommendations for day-to-day decision-making from a joint surgical and anaesthesiological point of view. The discussion centres on gastrointestinal surgery specifically."],["dc.identifier.doi","10.1007/s00423-011-0782-y"],["dc.identifier.isi","000290985700002"],["dc.identifier.pmid","21448724"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6624"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22953"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1435-2443"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Standard perioperative management in gastrointestinal surgery"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1280"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Theranostics"],["dc.bibliographiccitation.lastpage","1287"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Berger, Andreas W."],["dc.contributor.author","Schwerdel, Daniel"],["dc.contributor.author","Reinacher-Schick, Anke"],["dc.contributor.author","Uhl, Waldemar"],["dc.contributor.author","Algül, Hana"],["dc.contributor.author","Friess, Helmut"],["dc.contributor.author","Janssen, Klaus-Peter"],["dc.contributor.author","König, Alexander"],["dc.contributor.author","Ghadimi, Michael"],["dc.contributor.author","Gallmeier, Eike"],["dc.contributor.author","Bartsch, Detlef K."],["dc.contributor.author","Geissler, Michael"],["dc.contributor.author","Staib, Ludger"],["dc.contributor.author","Tannapfel, Andrea"],["dc.contributor.author","Kleger, Alexander"],["dc.contributor.author","Beutel, Alica"],["dc.contributor.author","Schulte, Lucas-Alexander"],["dc.contributor.author","Kornmann, Marko"],["dc.contributor.author","Ettrich, Thomas J."],["dc.contributor.author","Seufferlein, Thomas"],["dc.date.accessioned","2019-07-09T11:50:26Z"],["dc.date.available","2019-07-09T11:50:26Z"],["dc.date.issued","2019"],["dc.description.abstract","The most frequent malignancy of the pancreas is the pancreatic ductal adenocarcinoma (PDAC). Despite many efforts PDAC has still a dismal prognosis. Biomarkers for early disease stage diagnosis as a prerequisite for a potentially curative treatment are still missing. Novel blood-based markers may help to overcome this limitation. Methods: Prior to surgery plasma levels of thrombospondin-2 (THBS2), which was recently published as a novel biomarker, and CA19-9 from 52 patients with histologically proven PDAC were determined, circulating cell-free (cfDNA) was quantified. 15 patients with side-branch IPMNs without worrisome features and 32 patients with chronic pancreatitis served for comparison. Logit (logistic regression) models were used to test the performance of single biomarkers and biomarker combinations. Results: CA19-9 and THBS2 alone showed comparable c-statistics of 0.80 and 0.73, respectively, improving to 0.87 when combining these two markers. The c-statistic was further increased to 0.94 when combining CA19-9 and THBS2 with cfDNA quantification. This marker combination performed best for all PDAC stages but also for PDACs grouped by stage. The greatest improvement over CA19-9 was seen in the group of stage I PDAC, from 0.69 to 0.90 for the three marker combination. Conclusion:These data establish the combination of CA19-9, THBS2 and cfDNA as a composite liquid biomarker for non-invasive diagnosis of early-stage PDAC."],["dc.identifier.doi","10.7150/thno.29247"],["dc.identifier.pmid","30867830"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15940"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59773"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1838-7640"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.subject.ddc","610"],["dc.title","A Blood-Based Multi Marker Assay Supports the Differential Diagnosis of Early-Stage Pancreatic Cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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.artnumber","70"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Clinical Medicine"],["dc.bibliographiccitation.volume","8"],["dc.contributor.affiliation","Mewes, Caspar; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany,"],["dc.contributor.affiliation","Büttner, Benedikt; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany,"],["dc.contributor.affiliation","Hinz, José; \t\t \r\n\t\t Department of Anesthesiology and Intensive Care Medicine, Klinikum Region Hannover, D-30459 Hannover, Germany,"],["dc.contributor.affiliation","Alpert, Ayelet; \t\t \r\n\t\t Faculty of Medicine, Technion−Israeli Institute of Technology, 31096 Haifa, Israel,"],["dc.contributor.affiliation","Popov, Aron-Frederik; \t\t \r\n\t\t Department of Thoracic and Cardiovascular Surgery, University Medical Center, Eberhard Karls University, D-72076 Tuebingen, Germany,"],["dc.contributor.affiliation","Ghadimi, Michael; \t\t \r\n\t\t Department of General and Visceral Surgery, University Medical Center, Georg August University, D-37075 Goettingen, Germany,"],["dc.contributor.affiliation","Beissbarth, Tim; \t\t \r\n\t\t Department of Medical Bioinformatics, University Medical Center, Georg August University, D-37077 Goettingen, Germany,"],["dc.contributor.affiliation","Tzvetkov, Mladen; \t\t \r\n\t\t Department of Pharmacology, University Medical Center, Ernst-Moritz-Arndt-University, D-17487 Greifswald, Germany,"],["dc.contributor.affiliation","Jensen, Ole; \t\t \r\n\t\t Department of Clinical Pharmacology, University Medical Center, Georg August University, D-37075 Goettingen, Germany,"],["dc.contributor.affiliation","Runzheimer, Julius; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany,"],["dc.contributor.affiliation","Quintel, Michael; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany,"],["dc.contributor.affiliation","Shen-Orr, Shai; \t\t \r\n\t\t Faculty of Medicine, Technion−Israeli Institute of Technology, 31096 Haifa, Israel,"],["dc.contributor.affiliation","Bergmann, Ingo; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany,"],["dc.contributor.affiliation","Mansur, Ashham; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany,"],["dc.contributor.author","Mewes, Caspar"],["dc.contributor.author","Büttner, Benedikt"],["dc.contributor.author","Hinz, José Maria"],["dc.contributor.author","Alpert, Ayelet"],["dc.contributor.author","Popov, Aron-Frederik"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Tzvetkov, Mladen Vassilev"],["dc.contributor.author","Jensen, Ole"],["dc.contributor.author","Runzheimer, Julius"],["dc.contributor.author","Quintel, Michael I."],["dc.contributor.author","Shen-Orr, Shai"],["dc.contributor.author","Bergmann, Ingo"],["dc.contributor.author","Mansur, Ashham"],["dc.date.accessioned","2019-07-09T11:49:58Z"],["dc.date.available","2019-07-09T11:49:58Z"],["dc.date.issued","2019"],["dc.date.updated","2022-02-09T13:23:19Z"],["dc.description.abstract","Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is a coinhibitory checkpoint protein expressed on the surface of T cells. A recent study by our working group revealed that the rs231775 single nucleotide polymorphism (SNP) in the CTLA-4 gene was associated with the survival of patients with sepsis and served as an independent prognostic variable. To further investigate the impact of CTLA-4 genetic variants on sepsis survival, we examined the effect of two functional SNPs, CTLA-4 rs733618 and CTLA-4 rs3087243, and inferred haplotypes, on the survival of 644 prospectively enrolled septic patients. Kaplan⁻Meier survival analysis revealed significantly lower 90-day mortality for rs3087243 G allele carriers (n = 502) than for AA-homozygous (n = 142) patients (27.3% vs. 40.8%, p = 0.0024). Likewise, lower 90-day mortality was observed for TAA haplotype-negative patients (n = 197; compound rs733618 T/rs231775 A/rs3087243 A) than for patients carrying the TAA haplotype (n = 447; 24.4% vs. 32.9%, p = 0.0265). Carrying the rs3087243 G allele hazard ratio (HR): 0.667; 95% confidence interval (CI): 0.489⁻0.909; p = 0.0103) or not carrying the TAA haplotype (HR: 0.685; 95% CI: 0.491⁻0.956; p = 0.0262) remained significant covariates for 90-day survival in the multivariate Cox regression analysis and thus served as independent prognostic variables. In conclusion, our findings underscore the significance of CTLA-4 genetic variants as predictors of survival of patients with sepsis."],["dc.description.sponsorship","Volkswagen Foundation"],["dc.identifier.doi","10.3390/jcm8010070"],["dc.identifier.eissn","2077-0383"],["dc.identifier.pmid","30634576"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15817"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59664"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","MDPI"],["dc.relation.eissn","2077-0383"],["dc.relation.issn","2077-0383"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","CTLA-4 Genetic Variants Predict Survival in Patients with Sepsis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","27"],["dc.bibliographiccitation.journal","World Journal of Surgical Oncology"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Sprenger, Thilo"],["dc.contributor.author","Rothe, Hilka"],["dc.contributor.author","Jung, Klaus"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Conradi, Lena-Christin"],["dc.contributor.author","Ghadimi, B. Michael"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Liersch, Torsten"],["dc.date.accessioned","2018-11-07T08:44:09Z"],["dc.date.available","2018-11-07T08:44:09Z"],["dc.date.issued","2010"],["dc.description.abstract","Background: Response to preoperative radiochemotherapy (RCT) in patients with locally advanced rectal cancer is very heterogeneous. Pathologic complete response (pCR) is accompanied by a favorable outcome. However, most patients show incomplete response. The aim of this investigation was to find indications for risk stratification in the group of intermediate responders to RCT. Methods: From a prospective database of 496 patients with rectal adenocarcinoma, 107 patients with stage II/III cancers and intermediate response to preoperative 5-FU based RCT (ypT2/3 and TRG 2/3), treated within the German Rectal Cancer Trials were studied. Surgical treatment comprised curative (R0) total mesorectal excision (TME) in all cases. In 95 patients available for statistical analyses, residual transmural infiltration of the mesorectal compartment, nodal involvement and histolologic tumor grading were investigated for their prognostic impact on disease-free (DFS) and overall survival ( OS). Results: Residual tumor transgression into the mesorectal compartment (ypT3) did not influence DFS and OS rates ( p = 0.619, p = 0.602, respectively). Nodal involvement after preoperative RCT (ypN1/2) turned out to be a valid prognostic factor with decreased DFS and OS (p = 0.0463, p = 0.0236, respectively). Persistent tumor infiltration of the mesorectum ( ypT3) and histologic tumor grading of residual tumor cell clusters were strongly correlated with lymph node metastases after neoadjuvant treatment (p < 0.001). Conclusions: Advanced transmural tumor invasion after RCT does not affect prognosis when curative ( R0) resection is achievable. Residual nodal status is the most important predictor of individual outcome in intermediate responders to preoperative RCT. Furthermore, ypT stage and tumor grading turn out to be additional auxiliary factors. Future clinical trials for risk-adapted adjuvant therapy should be based on a synopsis of clinicopathologic parameters."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.1186/1477-7819-8-27"],["dc.identifier.isi","000277431000001"],["dc.identifier.pmid","20388220"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5680"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20132"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1477-7819"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Stage II/III rectal cancer with intermediate response to preoperative radiochemotherapy: Do we have indications for individual risk stratification?"],["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","46"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Clinical Medicine"],["dc.bibliographiccitation.volume","9"],["dc.contributor.affiliation","Mewes, Caspar; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany, caspar.mewes@med.uni-goettingen.de"],["dc.contributor.affiliation","Böhnke, Carolin; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany, boehnke.carolin@web.de"],["dc.contributor.affiliation","Alexander, Tessa; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany, tessa.alexander@med.uni-goettingen.de"],["dc.contributor.affiliation","Büttner, Benedikt; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany, benedikt.buettner@med.uni-goettingen.de"],["dc.contributor.affiliation","Hinz, José; \t\t \r\n\t\t Department of Anesthesiology and Intensive Care Medicine, Klinikum Region Hannover, D-30459 Hannover, Germany, jose.hinz@krh.eu"],["dc.contributor.affiliation","Popov, Aron-Frederik; \t\t \r\n\t\t Department of Thoracic and Cardiovascular Surgery, University Medical Center, Eberhard Karls University, D-72076 Tuebingen, Germany, aronf.popov@gmail.com"],["dc.contributor.affiliation","Ghadimi, Michael; \t\t \r\n\t\t Department of General and Visceral Surgery, University Medical Center, Georg August University, D-37075 Goettingen, Germany, mghadim@uni-goettingen.de"],["dc.contributor.affiliation","Beißbarth, Tim; \t\t \r\n\t\t Institute of Medical Bioinformatics, University Medical Center, Georg August University, D-37077 Goettingen, Germany, tim.beissbarth@ams.med.uni-goettingen.de"],["dc.contributor.affiliation","Raddatz, Dirk; \t\t \r\n\t\t Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center, Georg August University, D-37075 Goettingen, Germany, draddat@gwdg.de"],["dc.contributor.affiliation","Meissner, Konrad; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany, konrad.meissner@med.uni-goettingen.de"],["dc.contributor.affiliation","Quintel, Michael; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany, mquintel@med.uni-goettingen.de"],["dc.contributor.affiliation","Bergmann, Ingo; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany, ingo.bergmann@med.uni-goettingen.de"],["dc.contributor.affiliation","Mansur, Ashham; \t\t \r\n\t\t Department of Anesthesiology, University Medical Center, Georg August University, D-37075 Goettingen, Germany, ashham.mansur@med.uni-goettingen.de"],["dc.contributor.author","Mewes, Caspar"],["dc.contributor.author","Böhnke, Carolin"],["dc.contributor.author","Alexander, Tessa"],["dc.contributor.author","Popov, Aron-Frederik"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Büttner, Benedikt"],["dc.contributor.author","Hinz, José"],["dc.contributor.author","Ghadimi, Michael"],["dc.contributor.author","Raddatz, Dirk"],["dc.contributor.author","Meissner, Konrad"],["dc.contributor.author","Quintel, Michael"],["dc.contributor.author","Bergmann, Ingo"],["dc.contributor.author","Mansur, Ashham"],["dc.date.accessioned","2020-04-02T10:35:27Z"],["dc.date.available","2020-04-02T10:35:27Z"],["dc.date.issued","2019-12-24"],["dc.date.updated","2022-02-09T13:22:24Z"],["dc.description.abstract","Septic shock is a frequent life-threatening condition and a leading cause of mortality in intensive care units (ICUs). Previous investigations have reported a potentially protective effect of obesity in septic shock patients. However, prior results have been inconsistent, focused on short-term in-hospital mortality and inadequately adjusted for confounders, and they have rarely applied the currently valid Sepsis-3 definition criteria for septic shock. This investigation examined the effect of obesity on 90-day mortality in patients with septic shock selected from a prospectively enrolled cohort of septic patients. A total of 352 patients who met the Sepsis-3 criteria for septic shock were enrolled in this study. Body-mass index (BMI) was used to divide the cohort into 24% obese (BMI ≥ 30 kg/m2) and 76% non-obese (BMI < 30 kg/m2) patients. Kaplan-Meier survival analysis revealed a significantly lower 90-day mortality (31% vs. 43%; p = 0.0436) in obese patients compared to non-obese patients. Additional analyses of baseline characteristics, disease severity, and microbiological findings outlined further statistically significant differences among the groups. Multivariate Cox regression analysis estimated a significant protective effect of obesity on 90-day mortality after adjustment for confounders. An understanding of the underlying physiologic mechanisms may improve therapeutic strategies and patient prognosis."],["dc.description.sponsorship","University of Goettingen"],["dc.identifier.doi","10.3390/jcm9010046"],["dc.identifier.eissn","2077-0383"],["dc.identifier.pmid","31878238"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17053"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/63513"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","MDPI"],["dc.relation.eissn","2077-0383"],["dc.relation.issn","2077-0383"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Favorable 90-Day Mortality in Obese Caucasian Patients with Septic Shock According to the Sepsis-3 Definition"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","175628482110511"],["dc.bibliographiccitation.journal","Therapeutic Advances in Gastroenterology"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Azizian, Azadeh"],["dc.contributor.author","König, Alexander"],["dc.contributor.author","Hartmann, Amelie"],["dc.contributor.author","Schuppert, Frank"],["dc.contributor.author","Seif Amir Hosseini, Ali"],["dc.contributor.author","Kitz, Julia"],["dc.contributor.author","Ghadimi, Michael"],["dc.date.accessioned","2022-01-11T14:08:01Z"],["dc.date.available","2022-01-11T14:08:01Z"],["dc.date.issued","2021"],["dc.description.abstract","VIPoma, a neuroendocrine tumour mostly occurring in the human pancreas and producing high levels of vasoactive intestinal peptide, is a rare disease that presents with a wide spectrum of symptoms, including intense diarrhoea, hypokalaemia, and cardiac complications, with life-threatening consequences. In most cases, metastatic lesions are present at VIPoma diagnosis. Treatment options include symptomatic therapy, chemotherapy, radiation and surgery. Due to its low incidence, there are no evidence-based therapy recommendations to date. Here, we present a case of a 39-year-old woman with severe symptoms due to VIPoma of the pancreas with diffuse hepatic metastasis, who underwent simultaneous resection of the primary tumour, extensive liver resection and radiofrequency ablation. The patient was released in good health and was recurrence-free during 12 months surveillance. According to the existing literature and our own experience, surgical procedures appear to be the most promising therapy option for cases with diffuse hepatic metastasis, offering patients relief from their symptoms and (chemo)therapy-free time."],["dc.identifier.doi","10.1177/17562848211051132"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/97916"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-507"],["dc.relation.issn","1756-2848"],["dc.rights","CC BY-NC 4.0"],["dc.title","Surgical treatment of metastatic VIPoma: a case report"],["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","128"],["dc.bibliographiccitation.journal","BMC Medicine"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Mansur, Ashham"],["dc.contributor.author","Steinau, Maximilian"],["dc.contributor.author","Popov, Aron-Frederik"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Bauer, Martin"],["dc.contributor.author","Hinz, José Maria"],["dc.date.accessioned","2018-11-07T09:56:35Z"],["dc.date.available","2018-11-07T09:56:35Z"],["dc.date.issued","2015"],["dc.description.abstract","Background: Previous investigations have presumed a potential therapeutic effect of statin therapy in patients with acute respiratory distress syndrome (ARDS). Statins are expected to attenuate inflammation in the lungs of patients with ARDS due to their anti-inflammatory effects. Clinical investigations of the role of statin therapy have revealed contradictory results. This study aimed to investigate whether pretreatment and continuous therapy with statins in patients with sepsis-associated ARDS are associated with 28-day survival according to disease severity (mild, moderate, or severe). Methods: Patients with sepsis-associated ARDS from the surgical intensive care were enrolled in this prospective observational investigation. ARDS was classified into three groups (mild, moderate, and severe); 28-day mortality was recorded as the primary outcome variable and organ failure was recorded as secondary outcome variable. Sequential Organ Failure Assessment scores and the requirements for organ support were evaluated throughout the observational period to assess organ failure. Results: 404 patients with sepsis-associated ARDS were enrolled in this investigation. The distribution of the ARDS subgroups was 13 %, 59 %, and 28 % for mild, moderate, and severe disease, respectively. Statin therapy improved 28-day survival exclusively in the patients with severe ARDS compared with patients without statin therapy (88.5 % and 62.5 %, respectively; P = 0.0193). To exclude the effects of several confounders, we performed multivariate Cox regression analysis, which showed that statin therapy remained a significant covariate for mortality (hazard ratio, 5.46; 95 % CI, 1.38-21.70; P = 0.0156). Moreover, after carrying a propensity score-matching in the severe ARDS cohort, Kaplan-Meier survival analysis confirmed the improved 28-day survival among patients with statin therapy (P = 0.0205). Patients with severe ARDS who received statin therapy had significantly more vasopressor-free days compared with those without statin therapy (13 +/- 7 and 9 +/- 7, respectively; P = 0.0034), and they also required less extracorporeal membrane oxygenation (ECMO) therapy and had more ECMO-free days (18 +/- 9 and 15 +/- 9, respectively; P = 0.0873). Conclusions: This investigation suggests a beneficial effect of continuous statin therapy in patients with severe sepsis-associated ARDS and a history of prior statin therapy. Further study is warranted to elucidate this potential effect."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2015"],["dc.identifier.doi","10.1186/s12916-015-0368-6"],["dc.identifier.isi","000355790700001"],["dc.identifier.pmid","26033076"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13459"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36986"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1741-7015"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Impact of statin therapy on mortality in patients with sepsis-associated acute respiratory distress syndrome (ARDS) depends on ARDS severity: a prospective observational cohort study"],["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"]]