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Human peripheral blood cells (PB): Effect of Tocilizumab/MRA compared to methotrexate(MTX) treatments on rheumatoid arthritis(RA) patients.

ABSTRACT: This microarray study was conducted along with SATORI study, the clinical trial evaluated 125 patients with active RA with an inadequate response to low dose of MTX. Patients were allocated to receive either Tocilizumab(TCZ) 8 mg/kg every 4 weeks (TCZ group) or MTX 8 mg/week (MTX/control group) for 24 weeks. Gene expression profiles (GEP) of 112 patients - 54 patients from TCZ group and 58 patients from MTX group - were obtained in this study.

ORGANISM(S): Homo sapiens

PROVIDER: GSE35455 | GEO | 2014/01/29

SECONDARY ACCESSION(S): PRJNA152397

REPOSITORIES: GEO

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Human peripheral blood cells (PB): Effect of Tocilizumab/MRA compared to methotrexate(MTX) treatments on rheumatoid arthritis(RA) patients.

Project description:This microarray study was conducted along with SATORI study, the clinical trial evaluated 125 patients with active RA with an inadequate response to low dose of MTX. Patients were allocated to receive either Tocilizumab(TCZ) 8 mg/kg every 4 weeks (TCZ group) or MTX 8 mg/week (MTX/control group) for 24 weeks. Gene expression profiles (GEP) of 112 patients - 54 patients from TCZ group and 58 patients from MTX group - were obtained in this study. PB samples were collected directly into PAXGene tubes before and after the treatments. Total RNA was extracted using PAXGene Blood RNA Kit with the optimal on-column DNase digestion. Two-color microarray was used to directly compare the samples before versus after the treatment. Total RNA was amplified and amino allyl aRNA of the sample before/after treatments was further labeled with Cy3/Cy5. The labeled aRNAs (mixture of Cy3 and Cy5) was hybridized onto microarray slide. Dye swapping was done with each investigation to account for dye bias in microarray experiments.

2014-01-29 | E-GEOD-35455 | biostudies-arrayexpress

Effects of tocilizumab versus methotrexate therapy on gene expression profiles in the early rheumatoid arthrtis synovium

Project description:Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease that is characterized by the presence of inflammatory cytokines, including interleukin-6 (IL-6). Here, we investigated the global molecular effects of Tocilizumab, an approved humanized anti-IL6 Receptor antibody, versus Methotrexate therapy, in synovial biopsy samples collected prospectively in early RA before and 12 weeks after administration of the drug. The results were compared with our previous data, generated in prospective cohorts of Adalimumab- and Rituximab-treated (Methotrexate- and anti-TNF-resistant, respectively) RA patients. We found that Tocilizumab induces a significant down-regulation of genes included in specific pathways: cytokines & chemokines (e.g. IL-6, IL-7, IL-22, CCL8, CCL11, CCL13, CCL19, CCL20), and T cell activation. By contrast, Tocilizumab induces a significant up-regulation of genes associated with healing processes. These effects are significantly more pronounced as compared to Methotrexate, Rituximab, or Adalimumab therapies. By opposition to the effects of Adalimumab, Tocilizumab therapy does not induce a decreased expression of genes involved in cell proliferation. Paired synovial biopsy samples were obtained from the affected knee of early RA patients before and 12 weeks after initiation of Tocilizumab (n=12) or Methotrexate (n=8) therapy. SDAI remission criteria were computed prospectively before, 3 months and 6 months after administration of the drugs and patientsM-bM-^@M-^Y responses were defined according to their SDAI remission status at 6 months. Gene expression studies were performed using GeneChip Human Genome U133 Plus 2.0 arrays.

2013-12-30 | E-GEOD-45867 | biostudies-arrayexpress

Effects of tocilizumab versus methotrexate therapy on gene expression profiles in the early rheumatoid arthrtis synovium

2013-12-30 | GSE45867 | GEO

Expression data from proximal jejunum of WT vs. TLR2 KO mice after methotrexate (MTX) treatment

Project description:The role of innate immunity in modulating severity of chemotherapy-induced complications is so far unclear. The aim of this study was to determine how TLR2 may influence MTX-induced mucositis in the small intestine in mice. We used microarrays to assess gene expression profiles in proximal jejunum of WT vs. TLR2 KO mice after systemic treatment with MTX. Mucositis was induced by i.p. injection of MTX [40mg/kg BW/d] for 4 days in WT or TLR2 knockout (KO) mice. On day 7, mice were sacrificed and RNA was extracted from proximal jejunum (n=3 mice/group) and hybridized on Affymetrix microarrays.

2015-01-24 | E-GEOD-56426 | biostudies-arrayexpress

Effect of subcutaneous tocilizumab on gene expression of neutrophils in fibromyalgia patients

Project description:Differentially expressed genes were identified in neutrophils of 5 primary FM patients, when compared with controls. Differentially expressed genes were also identified in neutrophils of 2 primary FM patients at baseline and 12 weeks after tocilizumab treatment.

2023-04-24 | GSE229750 | GEO

Gene expressions of T cells in each developmental stages in healthy volunteers and patients with rheumatoid arthritis

Project description:We collected and compared samples from the cohort consisted of six groups as follows: methotrexate (MTX) monotherapy, combination therapy of MTX and infliximab (IFX), tocilizumab (TCZ) monotherapy, age- and gender-matched HC, and a small number of synovial fluid samples. In order to reduce variation due to the proportion of cells at each developmental stage, we performed transcriptome analysis after sorting CD4+ and CD8+ T cells according to developmental stage. We created a gene list that was significantly expressed in RA T cells, and revealed that pathways such as mTORC1, IL-2-stat5, Cell cycle and interferon-related genes were significantly enriched among them.

2019-06-06 | GSE118829 | GEO

Expression data from proximal jejunum of WT vs. TLR2 KO mice after methotrexate (MTX) treatment

2015-01-24 | GSE56426 | GEO

Gene expression profiling of melanoma cell lines (carrying NF1 loss-of-function) treated with DMSO (vehicle), MTX-216, MTX-211, trametinib, the combination of MTX-216 and trametinib, or pictilisib

Project description:In this study, we identified a multi-kinase inhibitor MTX-216 to be efficacious in blocking NF1 loss-of-function melanoma cells. To identify the mechansisms of action of MTX-216, we treated NF1 loss-of-function melanoma cell lines with MTX-216, MTX-211 (the structural analogue of MTX-216 that has no effect on melanoma cells) as well as commericial kinase inhibitors, trametinib and pictilisib, and compared their gene expression profiles.

2022-09-20 | GSE213588 | GEO

Differential gene expression profile may differentiate responders from non-reponders rheumatoid arthritis patients to methotrexate monotherapy and methotrexate plus TNF-blocker combined therapy

Project description:Oligo microarrays were used to access the transcription profiling of the rheumatoid arthritis patients under two different therapeutic approaches, aiming to evaluate if the cDNA microarray study is able to differentiate responders and non-responders to therapies. In the first experiment (MTX therapy) we analyzed 25 patients from which 8 were classified as MTX responders and 17 MTX non-responders. In the second experiment from the 17 MTX non-responder patients, 8 were non-responders and 9 were responders to additional anti-TNF therapy.

2011-12-31 | E-MEXP-3390 | biostudies-arrayexpress

Mitochondrial and oxidative stress genes are differentially expressed in neutrophils of sJIA patients treated with tocilizumab: a pilot microarray study

Project description:We hypothesised that neutrophil pathways could be also be important in the pathogenesis of sJIA. We therefore studied the gene profile in both PBMC and neutrophils of sJIA patients treated with tocilizumab. We demonstrate that neutrophils from sJIA patients showed significantly different changes in gene expression in response to tocilizumab.

2017-01-25 | GSE76492 | GEO

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