IL-17A inhibition by secukinumab induces early clinical, histopathologic, and molecular resolution of psoriasis.

Background: Hyperactivity of the IL-23/IL-17 axis is central to plaque psoriasis pathogenesis. Secukinumab, a fully human mAb that selectively inhibits IL-17A, is approved for treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis. Secukinumab improves the complete spectrum of psoriasis manifestations, with durable clinical responses beyond 5 years of treatment.

Omalizumab normalizes the gene expression signature of lesional skin in patients with chronic spontaneous urticaria: A randomized, double-blind, placebo-controlled study.

Background: Omalizumab, a humanized recombinant monoclonal anti-IgE antibody, proved to be effective in patients with chronic spontaneous urticaria (CSU), including severe and treatment-refractory CSU. Here, we report omalizumab's effect on gene expression in skin biopsies from CSU patients enrolled in a double-blind, placebo-controlled study.

Methods: Chronic spontaneous urticaria patients (18-75 years) were randomized to either 300 mg omalizumab (n = 20) or placebo (n = 10) administered s.

Canakinumab reverses overexpression of inflammatory response genes in tumour necrosis factor receptor-associated periodic syndrome.

Objective: To explore whether gene expression profiling can identify a molecular mechanism for the clinical benefit of canakinumab treatment in patents with tumour necrosis factor receptor-associated periodic syndrome (TRAPS).

Methods: Blood samples were collected from 20 patients with active TRAPS who received canakinumab 150 mg every 4 weeks for 4 months in an open-label proof-of-concept phase II study, and from 20 aged-matched healthy volunteers. Gene expression levels were evaluated in whole blood samples by microarray analysis for arrays passing quality control checks.

Gene expression profiling of immunomagnetically separated cells directly from stabilized whole blood for multicenter clinical trials.

Background: Clinically useful biomarkers for patient stratification and monitoring of disease progression and drug response are in big demand in drug development and for addressing potential safety concerns. Many diseases influence the frequency and phenotype of cells found in the peripheral blood and the transcriptome of blood cells. Changes in cell type composition influence whole blood gene expression analysis results and thus the discovery of true transcript level changes remains a challenge.

Robust and tissue-independent gender-specific transcript biomarkers.

Context: Correct gender assignment in humans at the molecular level is crucial in many scientific disciplines and applied areas.

Materials And Methods: Candidate gender markers were identified through supervised statistical analysis of genome wide microarray expression data from human blood samples (N = 123, 58 female, 65 male) as a training set. The potential of the markers to predict undisclosed tissue donor gender was tested on microarray data from 13 healthy and 11 cancerous human tissue collections (internal) and external datasets from samples of varying tissue origin.

Perturbation of microRNAs in rat heart during chronic doxorubicin treatment.

Anti-cancer therapy based on anthracyclines (DNA intercalating Topoisomerase II inhibitors) is limited by adverse effects of these compounds on the cardiovascular system, ultimately causing heart failure. Despite extensive investigations into the effects of doxorubicin on the cardiovascular system, the molecular mechanisms of toxicity remain largely unknown. MicroRNAs are endogenously transcribed non-coding 22 nucleotide long RNAs that regulate gene expression by decreasing mRNA stability and translation and play key roles in cardiac physiology and pathologies.

Optimal deconvolution of transcriptional profiling data using quadratic programming with application to complex clinical blood samples.

Large-scale molecular profiling technologies have assisted the identification of disease biomarkers and facilitated the basic understanding of cellular processes. However, samples collected from human subjects in clinical trials possess a level of complexity, arising from multiple cell types, that can obfuscate the analysis of data derived from them. Failure to identify, quantify, and incorporate sources of heterogeneity into an analysis can have widespread and detrimental effects on subsequent statistical studies.

Integrated epigenetics of human breast cancer: synoptic investigation of targeted genes, microRNAs and proteins upon demethylation treatment.

Background: The contribution of aberrant DNA methylation in silencing of tumor suppressor genes (TSGs) and microRNAs has been investigated. Since these epigenetic alterations are reversible, it became of interest to determine the effects of the 5-aza-2'-deoxycytidine (DAC) demethylation therapy in breast cancer at different molecular levels.

Methods And Findings: Here we investigate a synoptic model to predict complete DAC treatment effects at the level of genes, microRNAs and proteins for several human breast cancer lines.

A microarray analysis of full depth knee cartilage of ovariectomized rats.

Background: This short communication focuses the on articular cartilage and the subchondral bone, both of which play important roles in the development of osteoarthritis (OA). There are indications that estrogen-deficiency, as the post-menopausal state, accelerate the development of OA.

Findings: We investigated, which extracellular matrix (ECM) protein, proteases and different pro-inflammatory factors was up- or down-regulated in the knee joint tissue in response to estrogen-deficiency in rats induced by ovariectomy.

The molecular signature of oxidative metabolism and the mode of macrophage activation determine the shift from acute to chronic disease in experimental arthritis: critical role of interleukin-12p40.

Objective: Repeated injection of streptococcal cell wall (SCW) fragments results in chronic arthritis in mice. The objective of this study was to identify genes and pathways that determine disease progression based on gene expression profiling in this model.

Methods: Chronic arthritis was induced in mice by 4 injections of SCW fragments.