Ghadimi, Michael B.

[["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.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.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","8"],["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","Shen-Orr, Shai"],["dc.contributor.author","Bergmann, Ingo"],["dc.contributor.author","Mansur, Ashham"],["dc.date.accessioned","2019-07-09T11:45:59Z"],["dc.date.available","2019-07-09T11:45:59Z"],["dc.date.issued","2018"],["dc.description.abstract","Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a surface protein on T cells, that has an inhibitory effect on the host immune reaction and prevents overreaction of the immune system. Because the functional single-nucleotide polymorphism (SNP) rs231775 of the CTLA-4 gene is associated with autoimmune diseases and because of the critical role of the immune reaction in sepsis, we intended to examine the effect of this polymorphism on survival in patients with sepsis. 644 septic adult Caucasian patients were prospectively enrolled in this study. Patients were followed up for 90 days. Mortality risk within this period was defined as primary outcome parameter. Kaplan-Meier survival analysis revealed a significantly lower 90-day mortality risk among GG homozygous patients (n = 101) than among A allele carriers (n = 543; 22% and 32%, respectively; p = 0.03565). Furthermore, the CTLA-4 rs231775 GG genotype remained a significant covariate for 90-day mortality risk after controlling for confounders in the multivariate Cox regression analysis (hazard ratio: 0.624; 95% CI: 0.399–0.975; p = 0.03858). In conclusion, our study provides the first evidence for CTLA-4 rs231775 as a prognostic variable for the survival of patients with sepsis and emphasizes the need for further research to reveal potential functional associations between CTLA-4 and the immune pathophysiology of sepsis."],["dc.identifier.doi","10.1038/s41598-018-33246-9"],["dc.identifier.pmid","30310101"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15369"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59355"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","The CTLA-4 rs231775 GG genotype is associated with favorable 90-day survival in Caucasian patients with sepsis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","612774"],["dc.bibliographiccitation.journal","Frontiers in Cell and Developmental Biology"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Haas, Gwendolyn"],["dc.contributor.author","Fan, Shuang"],["dc.contributor.author","Ghadimi, Michael"],["dc.contributor.author","De Oliveira, Tiago"],["dc.contributor.author","Conradi, Lena-Christin"],["dc.date.accessioned","2021-06-22T13:36:45Z"],["dc.date.accessioned","2021-10-27T13:22:28Z"],["dc.date.available","2021-06-22T13:36:45Z"],["dc.date.available","2021-10-27T13:22:28Z"],["dc.date.issued","2021"],["dc.description.abstract","In modern anti-cancer therapy of metastatic colorectal cancer (mCRC) the anti-angiogenic treatment targeting sprouting angiogenesis is firmly established for more than a decade. However, its clinical benefits still remain limited. As liver metastases (LM) represent the most common metastatic site of colorectal cancer and affect approximately one-quarter of the patients diagnosed with this malignancy, its treatment is an essential aspect for patients' prognosis. Especially in the perioperative setting, the application of anti-angiogenic drugs represents a therapeutic option that may be used in case of high-risk or borderline resectable colorectal cancer liver metastases (CRCLM) in order to achieve secondary resectability. Regarding CRCLM, one reason for the limitations of anti-angiogenic treatment may be represented by vessel co-option (VCO), which is an alternative mechanism of blood supply that differs fundamentally from the well-known sprouting angiogenesis and occurs in a significant fraction of CRCLM. In this scenario, tumor cells hijack pre-existing mature vessels of the host organ independently from stimulating new vessels formation. This represents an escape mechanism from common anti-angiogenic anti-cancer treatments, as they primarily target the main trigger of sprouting angiogenesis, the vascular endothelial growth factor A. Moreover, the mechanism of blood supply in CRCLM can be deduced from their phenotypic histopathological growth pattern (HGP). For that, a specific guideline has already been implemented. These HGP vary not only regarding their blood supply, but also concerning their tumor microenvironment (TME), as notable differences in immune cell infiltration and desmoplastic reaction surrounding the CRCLM can be observed. The latter actually serves as one of the central criteria for the classification of the HGP. Regarding the clinically relevant effects of the HGP, it is still a topic of research whether the VCO-subgroup of CRCLM results in an impaired treatment response to anti-angiogenic treatment when compared to an angiogenic subgroup. However, it is well-proved, that VCO in CRCLM generally relates to an inferior survival compared to the angiogenic subgroup. Altogether the different types of blood supply result in a relevant influence on the patients' prognosis. This reinforces the need of an extended understanding of the underlying mechanisms of VCO in CRCLM with the aim to generate more comprehensive approaches which can target tumor vessels alternatively or even other components of the TME. This review aims to augment the current state of knowledge on VCO in CRCLM and other tumor entities and its impact on anti-angiogenic anti-cancer therapy."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.3389/fcell.2021.612774"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17843"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92098"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","2296-634X"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Different Forms of Tumor Vascularization and Their Clinical Implications Focusing on Vessel Co-option in Colorectal Cancer Liver Metastases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","591901"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Frontiers in Physiology"],["dc.bibliographiccitation.lastpage","20"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Fleischer, Johannes Robert"],["dc.contributor.author","Jodszuweit, Chiara Angelina"],["dc.contributor.author","Ghadimi, Michael"],["dc.contributor.author","De Oliveira, Tiago"],["dc.contributor.author","Conradi, Lena-Christin"],["dc.date.accessioned","2020-12-04T12:07:08Z"],["dc.date.accessioned","2021-10-27T13:22:22Z"],["dc.date.available","2020-12-04T12:07:08Z"],["dc.date.available","2021-10-27T13:22:22Z"],["dc.date.issued","2020"],["dc.description.abstract","Utilizing single-cell sequencing, recent studies were able to analyze at a greater resolution the heterogeneity of the vasculature and its complex composition in different tissues. Differing subpopulations have been detected, distinguishable only by their transcriptome. Designed to provide further insight into the heterogeneity of the functional vascular tissue, endothelial cells have been the main target of those studies. This review aims to present a synopsis of the variability of the different vascular beds, their endothelial variety, and the supporting cells that allow the vessels to serve their various purposes. Firstly, we are going to chart vascular tissue heterogeneity on a cellular level, describing endothelial diversity as well as stromal microenvironmental variety and interaction in a physiological setting. Secondly, we will summarize the current knowledge of pathological vessel formation in the context of cancer. Conventional anti-tumor therapeutic targets as well as anti-angiogenetic therapy is frequently limited by poor response of the tumor tissue. Reasons for moderate response and resistance to treatment can be found through different drivers of angiogenesis, different mechanisms of blood supply, but also in poorly understood tissue diversity. Based on this, we are comparing how pathologies alter the normal structure of vascular tissues highlighting the involved mechanisms. Lastly, illustrating the concept above, we will focus on the hepatic microenvironment, an organ of frequent metastatic spreading (e.g., from colorectal, breast, and lung cancers). We will address how the hepatic vasculature usually develops and subsequently we will describe how common liver metastases vary in their vasculature and the way they supply themselves (e.g., angiogenesis versus vessel co-option)."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2020"],["dc.identifier.doi","10.3389/fphys.2020.591901"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17677"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92089"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-042X"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Vascular Heterogeneity With a Special Focus on the Hepatic Microenvironment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","9887"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific reports"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Hinz, José Maria"],["dc.contributor.author","Büttner, Benedikt"],["dc.contributor.author","Kriesel, Fabian"],["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","Tzvetkov, Mladen Vassilev"],["dc.contributor.author","Bergmann, Ingo"],["dc.contributor.author","Mansur, Ashham"],["dc.date.accessioned","2019-07-09T11:43:39Z"],["dc.date.available","2019-07-09T11:43:39Z"],["dc.date.issued","2017-08-29"],["dc.description.abstract","A recent genome-wide association study showed that a genetic variant within the FER gene is associated with survival in patients with sepsis due to pneumonia. Because severe pneumonia is the main cause of acute respiratory distress syndrome (ARDS), we aimed to investigate the effect of the FER polymorphism rs4957796 on the 90-day survival in patients with ARDS due to pneumonia. An assessment of a prospectively collected cohort of 441 patients with ARDS admitted to three intensive care units at the University Medical Centre identified 274 patients with ARDS due to pneumonia. The 90-day mortality risk was recorded as the primary outcome parameter. Sepsis-related organ failure assessment (SOFA) scores and organ support-free days were used as the secondary variables. FER rs4957796 TT-homozygous patients were compared with C-allele carriers. The survival analysis revealed a higher 90-day mortality risk among T homozygotes than among C-allele carriers (p = 0.0144) exclusively in patients with severe ARDS due to pneumonia. The FER rs4957796 TT genotype remained a significant covariate for the 90-day mortality risk in the multivariate analysis (hazard ratio, 4.62; 95% CI, 1.58-13.50; p = 0.0050). In conclusion, FER rs4957796 might act as a prognostic variable for survival in patients with severe ARDS due to pneumonia."],["dc.identifier.doi","10.1038/s41598-017-08540-7"],["dc.identifier.pmid","28851893"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14613"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58938"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","The FER rs4957796 TT genotype is associated with unfavorable 90-day survival in Caucasian patients with severe ARDS due to pneumonia."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]