Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA101363 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We analyzed publicly available mucosal gene expression data from Crohn's disease (CD) patients pre- and post-infliximab therapy and found that a series of gene expression signature that remains abnormal even if patients achieve clinical remission. Using CMap approach to discover novel therapeutic target for untreatable mechanism of anti-TNFa mAb therapy, we have identified MEK inhibitor exhibiting negatively-correlated effects on reference signature match infliximab therapy untreatable signature. Our findings provide the rationale for testing MEK inhibitor to identify a novel mechanism of action for CD. Using an activated T cell trasnfer colitis model, a highly selective MEK inhibitor showed therapeutic efficacy and improved the histological changes. To dissect molecular mechanisms, we performed global gene expression profile by RNA-sequencing on the Ion Torrent platform to identify broad scale changes in gene expression treated with MEK inhibitor compared to anti-TNFa mAb.
2018-02-25 | GSE108052 | GEO
Project description:We analyzed publicly available mucosal gene expression data from Crohn's disease (CD) patients pre- and post-infliximab therapy and found that a series of gene expression signature that remains abnormal even if patients achieve clinical remission. Using CMap approach to discover novel therapeutic target for untreatable mechanism of anti-TNFa mAb therapy, we have identified MEK inhibitor exhibiting negatively-correlated effects on reference signature match infliximab therapy untreatable signature. Our findings provide the rationale for testing MEK inhibitor to identify a novel mechanism of action for CD. Gene expression profile was performed to analyze the gene modulation induced by a highly selective MEK inhibitor, and to evaluate whether it normalized reference residual CD signature in vitro.
2018-02-25 | GSE108050 | GEO
Project description:Objectives: We monitored the mRNA expression profiles of peripheral blood cells during treatment with a tumor necrosis factor-a inhibitor, infliximab, in patients with rheumatoid arthritis (RA). Using a DNA microarray analysis, we demonstrated a unique set of genes, with distinct baseline and post-treatment changes in expression between responders and non-responders to infliximab treatment.Methods: Using a customized low-density cDNA microarray and a reliable data collection system, we monitored the mRNA expression profiles of whole blood cells from 18 RA patients before and after the infusion of infliximab for up to 22 weeks. The clinical response to treatment with infliximab was determined using the American College of Rheumatology (ACR) response criteria, the disease activity score of 28 joints (DAS28), and individual clinical parameters. The patients were classified as responders or non-responders based on their ACR50% response at 22 weeks. Results: Approximately 15% of the total genes were found to exhibit a greater than 1.5-fold change, compared to their reference values, at one or more time points during the 22 weeks of infliximab therapy. The expression of inflammatory genes, such as interferon-related genes, was strongly correlated with the serum level of C-reactive protein and the DAS28. The increased expression of inflammatory genes in responders was normalized within 2 weeks and then remained at a normal level during the treatment period. In contrast, in the non-responders, the elevated expression at baseline, although it was significantly decreased at 2 weeks, returned to the baseline level after 14 weeks. In addition to inflammatory genes, we identified several groups of genes with distinct differences in expression between the responders and non-responders.Conclusions: Our results suggest that a customized low-density microarray is useful for monitoring mRNA expression profiles in peripheral blood cells, enabling us to identify a unique set of genes with differentially regulated expressions in responders and non-responders to a TNF inhibitor among patients with RA. Keywords: disease state analysis 18 RA Patients, We have collected blood samples into PAXgene tube systems for microarray measurement from patients as follows, just before first iv-injection of infliximab, 2 weeks, 14 weeks, and 22 weeks after first infliximab injection.
2007-10-09 | E-GEOD-8350 | biostudies-arrayexpress
Project description:objection: The immune inflammatory disorders rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (Ps) share common pathologic features and show responsiveness to anti-tumor necrosis factor (TNF) agents yet they are phenotypically distinct. The aim of this study was to examine if anti-TNF therapy is associated with divergent gene expression profiles in circulating cells and target tissues of patients with these diseases Method: Peripheral blood CD14+ and CD14- cells were isolated from 9 RA, 12 PsA and 10 Ps patients before and after infliximab (IFX) treatment
2014-10-29 | GSE57383 | GEO
Project description:objection: The immune inflammatory disorders rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (Ps) share common pathologic features and show responsiveness to anti-tumor necrosis factor (TNF) agents yet they are phenotypically distinct. The aim of this study was to examine if anti-TNF therapy is associated with divergent gene expression profiles in circulating cells and target tissues of patients with these diseases Method: Peripheral blood CD14+ and CD14- cells were isolated from 9 RA, 12 PsA and 10 Ps patients before and after infliximab (IFX) treatment.
2014-10-29 | GSE57405 | GEO
Project description:Objectives: We monitored the mRNA expression profiles of peripheral blood cells during treatment with a tumor necrosis factor-a inhibitor, infliximab, in patients with rheumatoid arthritis (RA). Using a DNA microarray analysis, we demonstrated a unique set of genes, with distinct baseline and post-treatment changes in expression between responders and non-responders to infliximab treatment.Methods: Using a customized low-density cDNA microarray and a reliable data collection system, we monitored the mRNA expression profiles of whole blood cells from 18 RA patients before and after the infusion of infliximab for up to 22 weeks. The clinical response to treatment with infliximab was determined using the American College of Rheumatology (ACR) response criteria, the disease activity score of 28 joints (DAS28), and individual clinical parameters. The patients were classified as responders or non-responders based on their ACR50% response at 22 weeks. Results: Approximately 15% of the total genes were found to exhibit a greater than 1.5-fold change, compared to their reference values, at one or more time points during the 22 weeks of infliximab therapy. The expression of inflammatory genes, such as interferon-related genes, was strongly correlated with the serum level of C-reactive protein and the DAS28. The increased expression of inflammatory genes in responders was normalized within 2 weeks and then remained at a normal level during the treatment period. In contrast, in the non-responders, the elevated expression at baseline, although it was significantly decreased at 2 weeks, returned to the baseline level after 14 weeks. In addition to inflammatory genes, we identified several groups of genes with distinct differences in expression between the responders and non-responders.Conclusions: Our results suggest that a customized low-density microarray is useful for monitoring mRNA expression profiles in peripheral blood cells, enabling us to identify a unique set of genes with differentially regulated expressions in responders and non-responders to a TNF inhibitor among patients with RA. Keywords: disease state analysis
2007-10-10 | GSE8350 | GEO
Project description:CD25 monoclonal antibody binding to the alpha-chain of the Interleukin-2 (IL-2) receptor, blocks high affinity IL-2 binding thereby preventing complete T cell activation and being of ample importance in transplantation medicine and potentially the treatment of autoimmune disease. However, CD25 antibodies do not only block T cell activation but also prevent activation induced cell death (AICD) attributing a dual function to IL-2. In this study, the modulation of the genomic expression profile of human peripheral blood mononuclear cells (PBMC) with therapeutic concentrations of humanized anti-CD25 mAb was investigated. PBMC were stimulated with CD3 antibody OKT-3 together with recombinant IL-2 in the absence or presence of anti-CD25 mAb. RNA was extracted and subjected to microarray analysis on U133A microarrays (Affymetrix). The expression profile revealed the up-regulation of 62 genes and down-regulation of 38 genes by anti-CD25 mAb, respectively. Experiment Overall Design: Peripheral blood mononuclear cells (PBMC) were stimulated for 8 or 16 hrs with 100 ng/ml OKT-3 together with 100 U/ml recombinant human interleukin-2 (rhIL-2) in the absence or presence of 30 µg/ml anti-CD25 antibody. RNA from cells under such treatment was isolated with Trizol and subjected to microarray analysis onto human U133A microarray following the Affymetrix protocol.
2009-05-11 | E-GEOD-15928 | biostudies-arrayexpress
Project description:Anti-TNF therapy has transformed the management of rheumatoid arthritis (RA); however little is known about its effects on cell mediated immune responses and TNF-inducible activity at the site of inflammation. Here, we used the tuberculin skin test (TST) as a standardised in vivo human challenge model to make systems level assessments of the effects of anti-TNF therapy in a prototypic cell mediated immune response. RA patients (treated with monoclonal anti-TNF antibodies (adalimumab or infliximab), the soluble TNF receptor etanercept or the standard therapy methotrexate) and healthy volunteers with immunological memory to Mycobacterium tuberculosis antigens were identified using an interferon-γ release assay of peripheral blood. Two units tuberculin or an equivalent volume of saline was injected into the forearm of study participants (n=50). After 72 hours, 3 mm skin punch biopsies were taken from the injection site and processed for whole genome transcriptional profiling by Agilent gene microarray.
2017-08-04 | E-MTAB-5093 | biostudies-arrayexpress
Project description:Infliximab, an anti-TNFa monoclonal antibody, is an effective treatment for ulcerative colitis (UC) inducing over 60% of patients to respond to treatment. Consequently, about 40% of patients do not respond. This study analyzed mucosal gene expression from patients enrolled in ACT1 to provide a predictive response signature for infliximab treatment. Keywords: predictive response signature
2009-08-25 | GSE12251 | GEO
Project description:objection: The immune inflammatory disorders rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (Ps) share common pathologic features and show responsiveness to anti-tumor necrosis factor (TNF) agents yet they are phenotypically distinct. The aim of this study was to examine if anti-TNF therapy is associated with divergent gene expression profiles in circulating cells and target tissues of patients with these diseases Method: Peripheral blood CD14+ and CD14- cells were isolated from 9 RA, 12 PsA and 10 Ps patients before and after infliximab (IFX) treatment. Between April 2007 and June 2009, 31 patients with active RA, PsA and Ps who were naïve to anti-TNF agents, were recruited from the Faculty Rheumatology Clinics at the University of Rochester Medical Center after informed, written consent was obtained in a protocol approved by the Research Subjects Review Board at the University of Rochester Medical Center. Of the 31 subjects, 9 had active RA and 12 had PsA despite treatment with Disease Modifying Anti-Rheumatic Drugs (DMARDs). Also, 10 patients with extensive Ps (>5% BSA) documented by a dermatologist, were enrolled and they were examined by a rheumatologist to exclude the presence of inflammatory arthritis. Nineteen healthy controls were also recruited.
2014-10-29 | E-GEOD-57405 | biostudies-arrayexpress