Identification of markers of responsiveness in rheumatoid arthritis patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: F Tron
PROVIDER: E-GEOD-11827 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:At a given time, rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms is still poorly understood. Because previous microarrays studies have only focused on late RA stages, we aimed to compare the biological and molecular profiles in early and long-standing (LS) RA. Synovial biopsies obtained by arthroscopy were performed in 4 early untreated RA patients, 4 LS treated RA patients and 7 control patients. Extracted mRNA were linearly amplified and used for large-scale gene expression profiling by cDNA arrays. By gene ontology analysis, the different gene combinations obtained by comparison of early, LS RA and normal synovium were used to identify the biological processes, molecular functions and pathways involved at each stage. Three combinations of 719, 116 and 52 transcripts dissociated respectively early from LS RA patients, early or LS RA from normal synovium. We identified several gene clusters and distinct molecular signatures specifically related to early or LS RA suggesting the involvement of different pathological mechanisms at each stage. Early and LS RA have distinct molecular signatures with the participation of different biological processes during the course of the disease. These results suggest that a better knowledge of the main biological processes involved at a given RA stage might help the rheumatologist to choose the more appropriate treatment. PBMC then RNA were extracted from synovial biopsies of 4 eraly RA patients, 4 long-standing RA patients and from 7 normal synovium used as control. Each sample was hybridized three times in different nylon membrane.
2010-06-25 | E-GEOD-13026 | biostudies-arrayexpress
Project description:C/EBPβ plays a major role in numerous biological processes but unfortunately its precise role is not still clear and conflicting studies showed that this transcription factor could have contradictory functions. These latter arise from the complexity of mechanisms regulating C/EBPβ activity. Indeed, C/EBPβ encodes an intronless gene that generates a single mRNA that is alternatively translated into two major isoforms of 35kDa (liver-enriched activator protein: LAP) and 20kDa (liver-enriched inhibitory protein: LIP). LAP is the active isoform of this transcription factor whereas LIP, a truncated isoform negatively regulate C/EBPβ-LAP-mediated gene expression. The main goal of our research was to understand how LAP and LIP isoforms governe C/EBPβ cellular functions with the identification of new genes and pathways regulated by these isoforms in the human Hep3B hepatoma cell line. For this purpose an original in vitro system characterized by a target genes induction with the activatory C/EBPß isoform LAP and a target genes repression with the inhibitory C/EBPß isoform (LIP) was used to identify the genuine C/EBPβ molecular signature. Using a cDNA microarray which provides a complete coverage of the liver transcriptome, we identified 676 genes inversely regulated by LAP and LIP. These selected genes are involved in many biological processes as the hepatic metabolism (cholesterol), detoxification, induction of apoptosis and negative regulation of the cell proliferation. According to the involvement of C/EBPβ in hepatic carcinogenesis we focused on cell cycle regulation and apoptosis. Through functional studies, we proved for the first time that LIP plays in favor of the survival of the Hep3B cells whereas LAP makes the cells more sensitive to staurosporine-induced cell death. Moreover, a lot of studies demonstrated that the anti-proliferative action of C/EBPβ mainly depends on RB protein. By studying the rate of Hep3B cells proliferation which overexpress LAP, we brought to the fore that this isoform would be able to induce a repression of the Hep3B cells line proliferation - a RB- and p53- negative cell line. Thus, LAP seems able to induce the repression of proliferation by a different metabolic way from the RB one. Keywords: comparison of cells expressing LAP or LIP RNA were extracted from 5 Hep3BLAPexpressing LAP, 5 Hep3BLAP control without expression of LAP, 5 Hep3BLIP expressing LIP and 5 Hep3BLIP control without epression of LIP. Each sample was hybridized once in 5 different nylon membranes.
2011-01-16 | E-GEOD-12410 | biostudies-arrayexpress
Project description:The aim of this study is to compare mild and advanced liver fibrosis gene expression profiling and to identify novel markers of fibrosis progression. By transcriptome analysis with a cDNA array virtually covering every transcript in liver, we compared transcript levels in mild (F1 Metavir score) and advanced (F4 Metavir score) fibrosis. A stringent selection identified a list of 16 transcripts which completely separated the 2 groups of patients (8 F1 and 8 F4). We report that dysregulations at the transcriptional level do exist between mild fibrosis (F1) and advanced fibrosis (F4). Keywords: fibrosis stage-dependent analysis Fibrosis samples were analyzed for 16 patients : 8 mild fibrosis (F1-1 to F1-8) and 8 advanced fibrosis (F4-1 to F4-8). All data in the current study were obtained from 3 separate hybridizations per RNA sample.
2008-05-24 | E-GEOD-11536 | biostudies-arrayexpress
Project description:The stringent response was defined in Lactococcus lactis through transcript profiling after the addition of a chemical inductor, the norvaline. Gene expression was measured in the exponential growth phase (reference sample) and at 1.6 h after norvaline addition. Four hundred and sixty one differentially expressed genes were identified and constituted the stringent response regulon. Keywords: stress response, time course Stringent response was imposed through norvaline addition during the growth of Lactococcus lactis IL1403 under controlled conditions (30 °C, pH 6.6, nitrogen atmosphere). Cell samples were harvested in exponential phase and 1.6 h after norvaline addition. Total RNA was extracted from these samples and radiolabelled cDNA were prepared and hybridized on nylon arrays. 2053 amplicons specific of Lactococcus lactis IL1403 genes were spotted twice on the array. The 2 time-points were analyzed simultaneously and 3 independent repetitions were performed.
2010-06-25 | E-GEOD-10254 | biostudies-arrayexpress
Project description:Background - Mammalians gamete production takes place in the testis but when they exit this organ, although spermatozoa have a specialized and distinct morphology, they are immotile and infertile. It is only after their travel in the epididymis that sperm acquire their motility and fertility. Epididymis can be divided in three gross morphological regions, head (caput), body (corpus) and tail (cauda), containing a long and unique convoluted tubule connecting the testis to the vas deferens. Results - In this study, the testis, the efferent ducts (vas efferens, VE), nine distinct successive epididymal segments and the deferent duct (vas deferens, VD) of four adult boars of known fertility were isolated and their mRNA extracted. The gene expression of each of these samples was analyzed using a pig generic 9K nylon microarray (AGENAE program; GEO accession number: GPL3729) spotted with 8931 clones derived from normalized cDNA banks from different pig tissues including testis and epididymis. Differentially expressed transcripts were obtained with moderated t-tests and F-tests and two data clustering algorithms based either on partitioning around medoïds (top down PAM) or hierarchical clustering (bottom up HCL) were combined for class discovery and gene expression analysis. Tissue samples analysis defined seven transcriptomic units: testis, vas efferens and five epididymal transcriptomic units. Meanwhile transcripts formed only four clusters related to the tissues. We have then used a specific statistical method to sort out genes specifically overexpressed (markers) in testis, VE or in each of the five transcriptomic units of the epididymis (including VD). Among these markers some well-known epididymal genes were retrieved while some were new genes or genes not yet reported in these boar tissues. The specific regional expression of some of these genes was further validated by PCR and Q-PCR. We also searched for specific pathways and functions using available gene ontology information. Conclusions - This study fulfilled the gap between those done in rodents and human, and provides tools that will be useful for further studies on the biochemical processes responsible for the formation and maintain of the epididymal regionalization and the development of a fertile spermatozoa. Keywords: tissue type comparaison 96 samples - 12 tissue samples from 4 boars
2010-06-24 | E-GEOD-15614 | biostudies-arrayexpress
Project description:Despite the increasing of available drugs in RA, the overall rate of non response is 30 to 40% of treated patients. To optimize the drug prescription and better elaborate the therapeutic strategies, gene profiling in PBMCs was used to predict the responsiveness to anakinra. Thirty two patients treated by anakinra (100mg/day s.c.) and méthotrexate, were categorized as responders whenever a change of Disease Activity Score 28 > 1.2 was obtained at 3 months. Blood from treated patients was collected at baseline. In 7 responders and 7 non responders, 51 mRNAs identified by microarray were expressed as a function of the response to treatment and an unsupervised hierarchical clustering perfectly separated responders from non responders. Keywords: anakinra effect
2008-06-19 | GSE11827 | GEO
Project description:In mammals, ovarian folliculogenesis leading to the ovulation of completely mature oocytes is a long and complex process that is regulated at different levels. The mechanisms that underlie the selection of one or several dominant follicles as well as the regulation of the number of ovulating follicles are largely unknown. In this project, we proposed to study the genetic determinism that underlies the difference of ovulation rate between species (cattle and pigs). Towards this purpose, we made a comparative transcriptomics study on granulosa cells. Pig and cattle comparison was achieved by a transcriptome analysis with a 9K nylon pig microarray (GPL3729) on granulosa cells from either small healthy antral follicles (SHF) or large healthy antral follicles (LHF). The images were quantified using AGscan software and the data were managed with BASE software. Statistical analysis was performed using R software. Transcriptomic analysis on pig and cattle evidenced 252 differentially expressed genes (FDR5%) between the two follicle classes and/or the two species. This research project which implicated three laboratories from INRA: M-BM-+ Laboratoire de GM-CM-)nM-CM-)tique Cellulaire M-BM-; (UMR444-LGC) , M-BM-+ Station dM-bM-^@M-^YAmM-CM-)lioration GM-CM-)nM-CM-)tique des Animaux M-BM-; (UR 631-SAGA) and M-BM-+ Physiologie des Comportements et de la reproduction M-BM-; (UMR 85-PRC) benefited from both European funding through SABRE project and French ANR funding through GenOvul project. Keywords: transcriptome analysis, pig, cattle, ovary, folliculogenesis, gene expression, cDNA microarray The data were obtained from 21 RNA samples: 10 small healthy follicles samples (6 for sows and 4 for cows) and 11 samples for large healthy follicles (6 for sows and 5 for cows). They were hybridized on a 9K pig nylon microarray (GPL3729).
2012-12-31 | E-GEOD-23335 | biostudies-arrayexpress
Project description:In mammals, ovarian folliculogenesis leading to the ovulation of completely mature oocytes is a long and complex process that is regulated at different levels. The mechanisms that underlie the selection of one or several dominant follicles as well as the regulation of the number of ovulating follicles are largely unknown. Atresia is a phenomenon which affects the majority of developing follicles. In this project, we proposed to study the gene regulation of small antral follicles that are either healthy or undergoing atresia in pigs). Towards this purpose, we made a comparative transcriptomics study on granulosa cells, using a 9K nylon pig microarray (GPL3729) on granulosa cells from either small healthy antral follicles (SHF) or small antretic follicles (SAF). The images were quantified using AGscan software and the data were managed with BASE software. Statistical analysis was performed using R software. Transcriptomic analysis evidenced 1682 (912) differentially expressed genes with a 5% (1%) FDR between the two follicle classes. This research project which implicated three laboratories from INRA: "Laboratoire de Genetique Cellulaire" (UMR444-LGC), "Station d'Amelioration Genetique des Animaux" (UR 631-SAGA) and "Physiologie des Comportements et de la reproduction" (UMR 85-PRC) benefited from both European funding through SABRE project and French ANR funding through GenOvul project. Keywords: transcriptome analysis, pig, cattle, ovary, folliculogenesis, gene expression, cDNA microarray The data were obtained from 13 RNA samples: 6 small healthy follicles samples and 7 small atretic follicles. They were hybridized on a 9K pig nylon microarray (GPL3729).
2012-12-31 | E-GEOD-24273 | biostudies-arrayexpress
Project description:In mammals, ovarian folliculogenesis leading to the ovulation of completely mature oocytes is a long and complex process that is regulated at different levels. The mechanisms that underlie the selection of one or several dominant follicles as well as the regulation of the number of ovulating follicles are largely unknown. In this project, we proposed to study the genetic determinism that underlies the difference of ovulation rate between species (cattle and pigs), by studying two processes that exist in ovary: follicular development and follicular atresia. Towards this purpose, we made a comparative transcriptomics study on granulosa cells. Pig and cattle comparison was achieved by a transcriptome analysis with a 9K nylon pig microarray (GPL3729) on granulosa cells from either small healthy antral follicles (SHF), small atretic follicles (SAF) or large healthy antral follicles (LHF). The images were quantified using AGscan software and the data were managed with BASE software. Statistical analysis was performed using R software. Transcriptomic analysis on pig and cattle evidenced 997 differentially expressed genes (FDR1%) between the three follicle classes and/or the two species. This research project which implicated three laboratories from INRA: "Laboratoire de Genetique Cellulaire" (UMR444-LGC) , "Station d'Amelioration Genetique des Animaux" (UR 631-SAGA) and "Physiologie des Comportements et de la reproduction" (UMR 85-PRC) benefited from both European funding through SABRE project and French ANR funding through GenOvul project. Keywords: transcriptome analysis, pig, cattle, ovary, folliculogenesis, gene expression, cDNA microarray The data were obtained from 34 RNA samples: 10 small healthy follicles samples (6 for sows and 4 for cows), 13 small atretic follicles samples (7 for sows and 6 for cows) and 11 samples for large healthy follicles (6 for sows and 5 for cows). They were hybridized on a 9K pig nylon microarray (GPL3729).
2012-12-31 | E-GEOD-24221 | biostudies-arrayexpress
Project description:Background: Systemic-Onset Juvenile Idiopathic Arthritis (SJIA) is a rare disease associated with dysregulated interleukin (IL)-1 activity. Objectives: To assess the efficacy and safety of Anakinra, an IL-1 receptor antagonist in SJIA and its effects on gene expression profiling. Methods: We conducted a multicenter, randomized, double-blind placebo-controlled trial. The primary objective was to compare the efficacy of a one-month treatment with anakinra (2 mg/kg subcutaneoulsy daily, maximum 100 mg) to a placebo between 2 groups of 12 SJIA patients each. Response was defined by a 30% improvement of the pediatric American College of Rheumatology criteria for JIA, resolution of systemic symptoms and a decrease of at least 50% of both C-reactive protein and erythrocyte sedimentation rate compared to baseline. An intention-to-treat analyze was performed. After Month 1 (M1), patients taking placebo were switched to Anakinra. Secondary objectives included tolerance and efficacy assessment for 12 months. Results: At M1, concluding the randomized trial, there was a significant difference in the response rate between patients treated with Anakinra (8/12 responders) and placebo (1/12) (p=0.003). The number of adverse events, mainly pain to injections, was similar between both groups. Ten patients from the placebo group switched to Anakinra at M1; nine were responders at M2. Between M1 and M12, six patients stopped treatment for an adverse event (Crohn’s disease, hepatitis), a lack of efficacy or a disease flare (2 cases each). Blood gene expression profiling at enrollment and upon follow-up allowed us to identify one set of dysregulated genes that reverted to normal values in the clinical responders and a second set, including interferon-inducible genes, that was induced by Anakinra. Conclusion: Anakinra is an effective treatment of SJIA. Its effect is associated with normalization of blood gene expression profiles in clinical responders and de novo induction of an interferon signature. (Clinical trials registration number: NCT00339157)
2009-12-31 | GSE17590 | GEO