We performed a phase I/II, randomized, double-blind, placebo-controlled dose-escalation study to examine the safety, immunogenicity, and biological effects of active immunization with interferon alpha-Kinoid (IFN-K) in systemic lupus erythematosus (SLE) patients. Women 18-50 years of age with mild to moderate SLE were immunized with three (n=10) or four doses (n=9) of 30, 60, 120, 240 microgram IFN-K or saline.
Down-regulation of interferon signature in systemic lupus erythematosus patients by active immunization with interferon α-kinoid.
Sex, Age, Specimen part, Disease, Disease stage, Treatment, Race
View SamplesInterferon-alpha Kinoid (IFN-K) is a therapeutic vaccine composed of IFN-alpha2b coupled to a carrier protein. In a phase I/II placebo-controlled trial, we observed that IFN-K significantly decreases the IFN gene signature in whole blood RNA samples from SLE patients (see GSE39088). Here, we analyzed extended follow-up data from IFN-K-treated patients, in terms of persistence of neutralizing anti-IFN Abs, gene expression profiling and safety.
Interferon α kinoid induces neutralizing anti-interferon α antibodies that decrease the expression of interferon-induced and B cell activation associated transcripts: analysis of extended follow-up data from the interferon α kinoid phase I/II study.
Sex, Specimen part, Disease, Disease stage, Subject, Time
View SamplesPatients with systemic lupus erythematosus are characterized by the spontaneous over-expression of interferon(IFN)-induced genes in peripheral blood RNA samples. In the present study, we wanted to study the evolution of the IFN gene signature in the peripheral blood of patients with lupus nephritis, before and after initiation of immunosuppressive therapy.
Interferon α kinoid induces neutralizing anti-interferon α antibodies that decrease the expression of interferon-induced and B cell activation associated transcripts: analysis of extended follow-up data from the interferon α kinoid phase I/II study.
Sex, Age, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View SamplesBackground: Blocking the action of the pro-inflammatory cytokine interleukin-1 (IL-1) reduces beta-cell secretory dysfunction and apoptosis in vitro, diabetes incidence in animal models of Type 1 diabetes mellitus (T1D), and glycaemia via improved beta-cell function in patients with T2D. We hypothesised that anakinra, a recombinant human IL-1 receptor antagonist, improves beta-cell function in patients with new-onset T1D. Methods: In an individually randomised, two-group parallel trial involving 14 European tertiary referral centers, 69 patients aged 18-35 with T1D, < 12 weeks of symptoms, and standard mixed meal test (MMT) stimulated C-peptide 200 pM were enrolled between January, 2009 and July, 2011 and assigned by centralised computer-generated blocked randomisation with locked computer-file concealment to treatment with 100 mg anakinra (n=35) subcutaneously once daily or placebo (n=34) for 9 months as add-on to conventional therapy. Participants and care-givers, but not data monitoring unit, were masked to group assignment. The primary end-point was change in the two-hour area-under-the-curve C-peptide response to MMT, and secondary end-points changes in insulin requirements, glycaemia, and inflammatory markers at one, three, six, and nine months. Findings: The study was prematurely terminated due to slow accrual and is closed to follow-up. No interim analysis was performed. Ten patients withdrew in the anakinra and eight in the placebo arm, leaving 25 and 26 patients to be analysed, respectively. There was no statistical difference in adverse event category reporting between arms. Interpretation: Anakinra-treatment in T1D was safe, but the trial failed to meet primary and secondary outcome measures.
Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset.
Subject, Time
View SamplesBackground: Blocking the action of the pro-inflammatory cytokine interleukin-1 (IL-1) reduces beta-cell secretory dysfunction and apoptosis in vitro, diabetes incidence in animal models of Type 1 diabetes mellitus (T1D), and glycaemia via improved beta-cell function in patients with T2D. We hypothesised that canakinumab, a monoclonal antibody to IL-1B, improves beta-cell function in patients with new-onset T1D. Methods: In an individually randomised, two-group parallel trial involving 12 sites in US, 69 patients aged 6-45 with T1D, < 12 weeks of symptoms, and assigned by centralised computer-generated blocked randomisation with locked computer-file concealment to treatment with 2 mg/kg (maximum 300 mg) canakinumab (n=45) or placebo (n=22) monthly for 12 months as add-on to conventional therapy. Participants and care-givers, but not data monitoring unit, were masked to group assignment. The primary end-point was change in the two-hour area-under-the-curve C-peptide response to MMT 12 months.
Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset.
Subject, Time
View SamplesThe cure rate for childhood ALL has improved considerably in part because therapy is routinely tailored to the predicted risk of relapse. Various clinical and laboratory variables are used in current risk-stratification schemes, but many children who fail therapy lack adverse prognostic factors at initial diagnosis. Using gene expression analysis, we have identified genes and pathways in a NCI high-risk childhood B-precursor ALL cohort at diagnosis that may play a role in early blast regression as correlated with the Day 7 marrow status. We have also identified a 47-probeset signature (representing 41 unique genes) that was predictive of long term outcome in our dataset as well as three large independent datasets of childhood ALL treated on different protocols.
Gene expression signatures predictive of early response and outcome in high-risk childhood acute lymphoblastic leukemia: A Children's Oncology Group Study [corrected].
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.
Specimen part, Cell line, Treatment
View SamplesWe compared TET1 and TET3 overexpressing cells to uninduced cells with endogenous levels of the respective transcript to determine global gene expression changes.
Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.
Specimen part, Treatment
View SamplesWe compared TET triple knockdown cells to control cells treated with non-targeting siRNAs to determine global gene expression changes.
Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.
Cell line, Treatment
View SamplesPatients with cytogenetically normal acute myeloid leukemia (CN-AML) show heterogeneous treatment outcomes. We used gene expression profiling to develop a gene signature that predicts overall survival (OS) in CN-AML. Based on data from 163 patients treated in the German AMLCG 1999 trial and analyzed on oligonucleotide microarrays, we used supervised principal component analysis to identify 86 probe sets (representing 66 different genes) which correlated with OS, and defined a prognostic score based on this signature. When applied to an independent cohort of 79 CN-AML patients, this continuous score remained a significant predictor for OS (hazard ratio [HR], 1.85; P=0.002), EFS (HR, 1.73; P=0.001), and RFS (HR, 1.76; P=0.025). It kept its prognostic value in multivariate analyses adjusting for age, FLT3 ITD and NPM1 status. In a validation cohort of 64 CN-AML patients treated on CALGB study 9621, the score also predicted OS (HR, 4.11; P<0.001), EFS (HR, 2.90; P<0.001), and RFS (HR, 3.14, P<0.001) and retained its significance in a multivariate model for OS. In summary, we present a novel gene expression signature that offers additional prognostic information for patients with CN-AML.
An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia.
No sample metadata fields
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