Chan, Andrew S.

[["dc.bibliographiccitation.firstpage","5356"],["dc.bibliographiccitation.issue","18"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","5366"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Zhang, C."],["dc.contributor.author","Doherty, Jennifer Anne"],["dc.contributor.author","Burgess, Stephen"],["dc.contributor.author","Hung, Rayjean J."],["dc.contributor.author","Lindstroem, Sara"],["dc.contributor.author","Kraft, Peter"],["dc.contributor.author","Gong, Jian"],["dc.contributor.author","Amos, Christopher I."],["dc.contributor.author","Sellers, Thomas A."],["dc.contributor.author","Monteiro, Alvaro N. A."],["dc.contributor.author","Chenevix-Trench, Georgia"],["dc.contributor.author","Bickeböller, Heike"],["dc.contributor.author","Risch, Angela"],["dc.contributor.author","Brennan, P. C."],["dc.contributor.author","McKay, James D."],["dc.contributor.author","Houlston, Richard S."],["dc.contributor.author","Landi, Maria Teresa"],["dc.contributor.author","Timofeeva, Maria N."],["dc.contributor.author","Wang, Y."],["dc.contributor.author","Heinrich, Joachim"],["dc.contributor.author","Kote-Jarai, Zsofia"],["dc.contributor.author","Eeles, Rosalind A."],["dc.contributor.author","Muir, Ken"],["dc.contributor.author","Wiklund, Fredrik"],["dc.contributor.author","Gronberg, Henrik"],["dc.contributor.author","Berndt, Sonja I."],["dc.contributor.author","Chanock, Stephen J."],["dc.contributor.author","Schumacher, Frederick R."],["dc.contributor.author","Haiman, Christopher A."],["dc.contributor.author","Henderson, Brian E."],["dc.contributor.author","Al Olama, Ali Amin"],["dc.contributor.author","Andrulis, Irene L."],["dc.contributor.author","Hopper, John L."],["dc.contributor.author","Chang-Claude, Jenny"],["dc.contributor.author","John, Esther M."],["dc.contributor.author","Malone, Kathleen E."],["dc.contributor.author","Gammon, Marilie D."],["dc.contributor.author","Ursin, Giske"],["dc.contributor.author","Whittemore, Alice S."],["dc.contributor.author","Hunter, David J."],["dc.contributor.author","Gruber, Stephen B."],["dc.contributor.author","Knight, Julia A."],["dc.contributor.author","Hou, Lifang"],["dc.contributor.author","Le Marchand, Loic"],["dc.contributor.author","Newcomb, Polly A."],["dc.contributor.author","Hudson, Thomas J."],["dc.contributor.author","Chan, Andrew T."],["dc.contributor.author","Li, L. I."],["dc.contributor.author","Woods, Michael O."],["dc.contributor.author","Ahsan, Habibul"],["dc.contributor.author","Pierce, Brandon L."],["dc.date.accessioned","2018-11-07T09:51:38Z"],["dc.date.available","2018-11-07T09:51:38Z"],["dc.date.issued","2015"],["dc.description.abstract","Epidemiological studies have reported inconsistent associations between telomere length (TL) and risk for various cancers. These inconsistencies are likely attributable, in part, to biases that arise due to post-diagnostic and post-treatment TL measurement. To avoid such biases, we used a Mendelian randomization approach and estimated associations between nine TL-associated SNPs and risk for five common cancer types (breast, lung, colorectal, ovarian and prostate cancer, including subtypes) using data on 51 725 cases and 62 035 controls. We then used an inverse-variance weighted average of the SNP-specific associations to estimate the association between a genetic score representing long TL and cancer risk. The long TL genetic score was significantly associated with increased risk of lung adenocarcinoma (P = 6.3 x 10(-15)), even after exclusion of a SNP residing in a known lung cancer susceptibility region (TERT-CLPTM1L) P = 6.6 x 10(-6)). Under Mendelian randomization assumptions, the association estimate [odds ratio (OR) = 2.78] is interpreted as the OR for lung adenocarcinoma corresponding to a 1000 bp increase in TL. The weighted TL SNP score was not associated with other cancer types or subtypes. Our finding that genetic determinants of long TL increase lung adenocarcinoma risk avoids issues with reverse causality and residual confounding that arise in observational studies of TL and disease risk. Under Mendelian randomization assumptions, our finding suggests that longer TL increases lung adenocarcinoma risk. However, caution regarding this causal interpretation is warranted in light of the potential issue of pleiotropy, and a more general interpretation is that SNPs influencing telomere biology are also implicated in lung adenocarcinoma risk."],["dc.identifier.doi","10.1093/hmg/ddv252"],["dc.identifier.isi","000361317200024"],["dc.identifier.pmid","26138067"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12147"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35955"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1460-2083"],["dc.relation.issn","0964-6906"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Genetic determinants of telomere length and risk of common cancers: a Mendelian randomization 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"]]

[["dc.bibliographiccitation.artnumber","e85"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Neurology® neuroimmunology & neuroinflammation"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Hoepner, Robert"],["dc.contributor.author","Faissner, Simon"],["dc.contributor.author","Klasing, Anja"],["dc.contributor.author","Schneider, Ruth"],["dc.contributor.author","Metz, Imke"],["dc.contributor.author","Bellenberg, Barbara"],["dc.contributor.author","Lukas, Carsten"],["dc.contributor.author","Altmeyer, Peter"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Chan, Andrew"],["dc.date.accessioned","2016-08-23T08:49:19Z"],["dc.date.accessioned","2021-10-27T13:20:42Z"],["dc.date.available","2016-08-23T08:49:19Z"],["dc.date.available","2021-10-27T13:20:42Z"],["dc.date.issued","2015-06-01"],["dc.description.abstract","not available"],["dc.identifier.doi","10.1212/NXI.0000000000000085"],["dc.identifier.fs","611967"],["dc.identifier.pmid","25798449"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13596"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/91978"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.issn","2332-7812"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY-NC-ND 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/3.0"],["dc.title","Progressive multifocal leukoencephalopathy during fumarate monotherapy of psoriasis."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2517"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","2530"],["dc.bibliographiccitation.volume","132"],["dc.contributor.author","Cotte, S."],["dc.contributor.author","von Ahsen, Nicolas"],["dc.contributor.author","Kruse, Niels"],["dc.contributor.author","Huber, B."],["dc.contributor.author","Winkelmann, Alexander"],["dc.contributor.author","Zettl, Uwe K."],["dc.contributor.author","Starck, Michaela"],["dc.contributor.author","Koenig, N."],["dc.contributor.author","Tellez, N."],["dc.contributor.author","Doerr, J."],["dc.contributor.author","Paul, Friedemann"],["dc.contributor.author","Zipp, Frauke"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Koepsell, Hermann"],["dc.contributor.author","Pannek, H."],["dc.contributor.author","Montalban, Xavier"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Chan, A."],["dc.date.accessioned","2018-11-07T11:24:34Z"],["dc.date.available","2018-11-07T11:24:34Z"],["dc.date.issued","2009"],["dc.description.abstract","Escalation therapy with mitoxantrone (MX) in highly active multiple sclerosis is limited by partially dose-dependent side-effects. Predictors of therapeutic response may result in individualized risk stratification and MX dosing. ATP-binding cassette-transporters ABCB1 and ABCG2 represent multi-drug resistance mechanisms involved in active cellular MX efflux. Here, we investigated the role of ABC-gene single nucleotide polymorphisms (SNPs) for clinical MX response, corroborated by experimental in vitro and in vivo data. Frequencies of ABCB1 2677GT, 3435CT and five ABCG2-SNPs were analysed in 832 multiple sclerosis patients (Germany, Spain) and 264 healthy donors. Using a flow-cytometry-based in vitro assay, MX efflux in leukocytes from individuals with variant alleles in both ABC-genes (designated genotype ABCB1/ABCG2-L(ow), 22.2 of patients) was 37.7 lower than from individuals homozygous for common alleles (ABCB1/ABCG2-H(igh), P 0.05, 14.8 of patients), resulting in genotype-dependent MX accumulation and cell death. Addition of glucocorticosteroids (GCs) inhibited MX efflux in vitro. ABC-transporters were highly expressed in leukocyte subsets, glial and neuronal cells as well as myocardium, i.e. cells/tissues potentially affected by MX therapy. In vivo significance was further corroborated in experimental autoimmune encephalomyelitis in Abcg2(/) animals. Using a MX dose titrated to be ineffective in wild-type animals, disease course and histopathology in Abcg2(/) mice were strongly ameliorated. Retrospective clinical analysis in MX monotherapy patients (n 155) used expanded disability status scale, relapse rate and multiple sclerosis functional composite as major outcome parameters. The clinical response rate [overall 121 of 155 patients (78.1)] increased significantly with genotypes associated with decreasing ABCB1/ABCG2-function [ABCB1/ABCG2-H 15/24 (62.5) responders, ABCB1/ABCG2-I(ntermediate) 78/98 (79.6), ABCB1/ABCG2-L 28/33 (84.8), exact Cochran-Armitage test P 0.039]. The odds ratio for response was 1.9 (95 CI 1.03.5) with each increase in ABCB1/ABCG2 score (from ABCB1/ABCG2-H to I-, and I to L). In 36 patients with severe cardiac or haematological side effects no statistically relevant difference in genotype frequency was observed. However, one patient with biopsy proven cardiomyopathy only after 24 mg/m(2) MX exhibited a rare genotype with variant, partly homozygous alleles in 3 ABC-transporter genes. In conclusion, SNPs in ABC-transporter genes may serve as pharmacogenetic markers associated with clinical response to MX therapy in multiple sclerosis. Combined MX/GC-treatment warrants further investigation."],["dc.description.sponsorship","Merck Serono, Germany"],["dc.identifier.doi","10.1093/brain/awp164"],["dc.identifier.isi","000269963600021"],["dc.identifier.pmid","19605531"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6073"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56436"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0006-8950"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","ABC-transporter gene-polymorphisms are potential pharmacogenetic markers for mitoxantrone response in multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","293"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","MULTIPLE SCLEROSIS"],["dc.bibliographiccitation.lastpage","302"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Blecharz, Kinga G."],["dc.contributor.author","Haghikia, Aiden"],["dc.contributor.author","Stasiolek, Mariusz"],["dc.contributor.author","Kruse, Niels"],["dc.contributor.author","Drenckhahn, Detlev"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Roewer, Norbert"],["dc.contributor.author","Chan, Andrew"],["dc.contributor.author","Foerster, Carola Y."],["dc.date.accessioned","2018-11-07T08:45:36Z"],["dc.date.available","2018-11-07T08:45:36Z"],["dc.date.issued","2010"],["dc.description.abstract","Compromised blood-brain barrier integrity is a major hallmark of active multiple sclerosis (MS). Alterations in brain endothelial tight junction protein and gene expression occur early during neuroinflammation but there is little known about the underlying mechanisms. In this study, we analysed barrier compromising effects of sera from MS patients and barrier restoring effects of glucocorticoids on blood-brain barrier integrity in vitro. cEND murine brain microvascular endothelial cell monolayers were incubated with sera from patients in active phase of disease or in relapse. Data were compared with effects of the glucocorticoid dexamethasone alone or in combination with MS sera on barrier integrity. Tight junction protein levels and gene expression were evaluated concomitant with barrier integrity. We reveal down-regulation of claudin-5 and occludin protein and mRNA and an accompanying upregulation in expression of matrix metalloproteinase MMP-9 after incubation with serum from active disease and remission and also a minor reconstitution of barrier functions related to dexamethasone treatment. Moreover, we for the first time describe downregulation of claudin-5 and occludin protein after incubation of cEND cells with sera from patients in remission phase of MS. Our findings reveal direct and differential effects of MS sera on blood-brain barrier integrity."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [SFB688-TPA5, SFB-TPA1 RG]"],["dc.identifier.doi","10.1177/1352458509358189"],["dc.identifier.isi","000275179200004"],["dc.identifier.pmid","20203147"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13047"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20482"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Sage Publications Ltd"],["dc.relation.issn","1352-4585"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Glucocorticoid effects on endothelial barrier function in the murine brain endothelial cell line cEND incubated with sera from patients with multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","14"],["dc.contributor.author","Hoepner, Robert"],["dc.contributor.author","Bagnoud, Maud"],["dc.contributor.author","Pistor, Maximilian"],["dc.contributor.author","Salmen, Anke"],["dc.contributor.author","Briner, Myriam"],["dc.contributor.author","Synn, Helen"],["dc.contributor.author","Schrewe, Lisa"],["dc.contributor.author","Guse, Kirsten"],["dc.contributor.author","Ahmadi, Farhad"],["dc.contributor.author","Demir, Seray"],["dc.contributor.author","Laverick, Louis"],["dc.contributor.author","Gresle, Melissa"],["dc.contributor.author","Worley, Paul"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Butzkueven, Helmut"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Metz, Imke"],["dc.contributor.author","Lühder, Fred"],["dc.contributor.author","Chan, Andrew"],["dc.date.accessioned","2019-07-09T11:51:33Z"],["dc.date.available","2019-07-09T11:51:33Z"],["dc.date.issued","2019"],["dc.description.abstract","The limited efficacy of glucocorticoids (GCs) during therapy of acute relapses in multiple sclerosis (MS) leads to long-term disability. We investigated the potential of vitamin D (VD) to enhance GC efficacy and the mechanisms underlying this VD/GC interaction. In vitro, GC receptor (GR) expression levels were quantified by ELISA and induction of T cell apoptosis served as a functional readout to assess synergistic 1,25(OH)2D3 (1,25D)/GC effects. Experimental autoimmune encephalomyelitis (MOG35-55 EAE) was induced in mice with T cell-specific GR or mTORc1 deficiency. 25(OH)D (25D) levels were determined in two independent cohorts of MS patients with stable disease or relapses either responsive or resistant to GC treatment (initial cohort: n = 110; validation cohort: n = 85). Gene expression of human CD8+ T cells was analyzed by microarray (n = 112) and correlated with 25D serum levels. In vitro, 1,25D upregulated GR protein levels, leading to increased GC-induced T cell apoptosis. 1,25D/GC combination therapy ameliorated clinical EAE course more efficiently than respective monotherapies, which was dependent on GR expression in T cells. In MS patients from two independent cohorts, 25D deficiency was associated with GC-resistant relapses. Mechanistic studies revealed that synergistic 1,25D/GC effects on apoptosis induction were mediated by the mTOR but not JNK pathway. In line, 1,25D inhibited mTORc1 activity in murine T cells, and low 25D levels in humans were associated with a reduced expression of mTORc1 inhibiting tuberous sclerosis complex 1 in CD8+ T cells. GR upregulation by 1,25D and 1,25D/GC synergism in vitro and therapeutic efficacy in vivo were abolished in animals with a T cell-specific mTORc1 deficiency. Specific inhibition of mTORc1 by everolimus increased the efficacy of GC in EAE. 1,25D augments GC-mediated effects in vitro and in vivo in a T cell-specific, GR-dependent manner via mTORc1 inhibition. These data may have implications for improvement of anti-inflammatory GC therapy."],["dc.identifier.doi","10.1007/s00401-019-02018-8"],["dc.identifier.pmid","31030237"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16149"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59968"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1432-0533"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Vitamin D increases glucocorticoid efficacy via inhibition of mTORC1 in experimental models of multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1189"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","MULTIPLE SCLEROSIS"],["dc.bibliographiccitation.lastpage","1192"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Chan, A."],["dc.contributor.author","Decard, B. F."],["dc.contributor.author","Franke, C."],["dc.contributor.author","Grummel, Verena"],["dc.contributor.author","Zhou, D."],["dc.contributor.author","Schottstedt, Volkmar"],["dc.contributor.author","Toyka, Klaus V."],["dc.contributor.author","Hemmer, Bernhard"],["dc.contributor.author","Gold, Ralf"],["dc.date.accessioned","2018-11-07T08:38:45Z"],["dc.date.available","2018-11-07T08:38:45Z"],["dc.date.issued","2010"],["dc.description.abstract","Objective: To investigate myelin autoantibodies before first disease manifestation using different detection methods. Methods: Patients with multiple sclerosis who had donated blood at a time prior to development of clinically isolated syndrome were identified via the German National Multiple Sclerosis Society. Control sera were obtained from age- and gender-matched blood donors. IgG-/IgM-antibodies against the extracellular part of native, cell surface-expressed myelin oligodendrocyte glycoprotein were detected by flow cytometry. Antibodies against linear epitopes were identified by immunoblot using recombinant myelin oligodendrocyte glycoprotein (aa1-125) and human myelin basic protein preparations. Results: Fifty eight serum samples from 25 patients covering an interval of 7.3 years-2 months prior to disease onset were available. Longitudinal investigations were performed in 19 patients (2-14 samples per patient, 7 years-2 months prior to disease onset). No significant differences in the prevalence or titres of anti-myelin antibodies were detected between sera of preclinical individuals and healthy donors by either flow cytometry or immunoblot. There was no correlation between interval before clinically isolated syndrome and autoantibody status. Occurrence of antibodies was not associated with symptomatology/severity of clinically isolated syndrome. Conclusion: Neither anti-myelin autoantibodies against cell surface-expressed native myelin oligodendrocyte glycoprotein nor against linear epitopes have a predictive or discriminative role during the preclinical disease phase for developing clinically isolated syndrome or multiple sclerosis later in life."],["dc.identifier.doi","10.1177/1352458510376406"],["dc.identifier.isi","000282332100005"],["dc.identifier.pmid","20685767"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12973"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18831"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Sage Publications Ltd"],["dc.relation.issn","1352-4585"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Serum antibodies to conformational and linear epitopes of myelin oligodendrocyte glycoprotein are not elevated in the preclinical phase of multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]