Project description:We investigated the gene expression changes in a library of small cell lung carcinoma (SCLC) patient-derived xenograft (PDX) models.
Project description:We aimed to identify the differences between these two subtypes of lung cancers and their differentially clinical treatment. Through functional analysis, we obtained differentially expressed proteins which might be assossciated with lung cancer treatment.
Project description:Age-related hearing (ARHL) loss affects a large part of the human population with a major impact on our aging societies. Yet, underlying mechanisms are not understood, and no validated therapy or prevention exists. NADPH oxidases (NOX), are important sources of reactive oxygen species (ROS) in the cochlea and might therefore be involved in the pathogenesis of ARHL. Here we investigate ARHL in a mouse model. Wild type mice showed early loss of hearing and cochlear integrity, while animals deficient in the NOX subunit p22phox remained unaffected up to six months. Genes of the excitatory pathway were down-regulated in p22phox-deficient auditory neurons. Our results demonstrate that NOX activity leads to upregulation of genes of the excitatory pathway, to excitotoxic cochlear damage, and ultimately to ARHL. In the absence of functional NOXs, aging mice conserve hearing and cochlear morphology. Our study offers new insights into pathomechanisms and future therapeutic targets of ARHL.
Project description:Fibrotic changes in the myocardium and cardiac arrhythmias represent fatal complications in rheumatic disease systemic sclerosis (SSc), however the underlying mechanisms remain elusive. Fos-related antigen-2 (Fosl-2) has been implicated in development of organ fibrosis. Mice overexpressing Fosl-2 (Fosl-2tg) showed interstitial cardiac fibrosis, disorganized connexin43/40 in intercalated discs and deregulated expression of genes controlling conduction system. Fosl-2tg mice developed higher heart rate (HR), prolonged QT intervals, arrhythmias with prevalence of premature ventricular contractions, ventricular tachycardias, II-degree atrio-ventricular blocks and reduced HR variability. Following stimulation with isoproterenol Fosl-2tg mice showed impaired HR response. To assess the role of inflammation in cardiac fibrosis we used Rag2-/-Fosl-2tg mice lacking T/B cells. These mice showed no myocardial fibrosis and ECG abnormalities. Transcriptomics analysis of cardiac Rag-2-/-Fosl-2wt/Rag2-/-Fosl-2tg/Fosl-2tg fibroblasts revealed that systemic inflammation triggered fibrotic and arrhythmogenic alterations while Fosl-2-overexpression mediated profibrotic signature. In human cardiac fibroblasts FOSL-2-overexpression enhanced myofibroblast signature under proinflammatory or profibrotic stimuli. These results demonstrate that under immunofibrotic conditions activator protein 1 transcription factor component Fosl-2 exaggerates myocardial fibrosis, arrhythmias and aberrant response to stress.
Project description:As part of the ENCODE consortium the GENCODE project is producing a reference gene set through manual and automated gene prediction. Selected transcript models are verified experimentally by RT-PCR amplification followed by sequencing. In batch IX, a set of de novo transcript models was tested aiming to incorporate new long non-coding RNA models into the GENCODE annotation. The original set was built with Cufflinks from ENCODE RNAseq data derived from 15 cell lines by the Gingeras (CSHL) and Wold (CalTech) labs. A subset of multiexonic transcripts not overlapping the GENCODE v10 annotation was selected for this experiment.
Project description:As part of the ENCODE consortium the GENCODE project is producing a reference gene set through manual and automated gene prediction. Selected transcript models are verified experimentally by RT-PCR amplification of at least one of their unique splice junctions followed by sequencing. Batch X targets manually annotated transcripts from GENCODE v11 (released Feb 2012) with novel or putative status, non-pseudogene biotype and unique splice junctions not validated previously.
Project description:Here we present genome-wide copy number variation data on two vehicle treated and two CC214-2 (an mTOR kinase inhibitor) resistant GlioBlastoma Multiforme 39 (GBM39) xenografts, showing the absence of significant differences between the two groups, demonstrating that resistance to CC214-2 is due to adaptation rather than gene mutations. The genomic DNA extracted from the 4 xenografts samples was analysed with genome-wide Affymetrix SNP6.0 array
Project description:As part of the ENCODE consortium the GENCODE project is producing a reference gene set through manual and automated gene prediction. Selected transcript models are verified experimentally by RT-PCR amplification of at least one of their unique splice junctions followed by sequencing. The experiment targets are manually annotated transcripts with novel or putative status, non-pseudogene biotype and unique splice junctions not validated previously. For Batch XI 966 splice junctions from GENCODE13 (released July 2012) and 640 splice junctions from GENCODE14 (released October 2012) were chosen for experimental verification.
Project description:Here we present gene expression analysis data on two vehicle treated and two CC214-2 (an mTOR kinase inhibitor) resistant GlioBlastoma Multiforme 39 (GBM39) xenografts, showing that the expressioin profiles of 88 genes are significantly different between the two groups. GBM39 primary neurospheres were cultured in standard cancer stem cell medium conditions and then were injected in the mice flanks to generate xenograft tissues. Mice carrying CC214-2 resistant xenografts were treated with a solution of CC214-2 once every two days, by gavage, for 40 days. Total RNA was extracted from GBM39 control and CC214-2 resistant xenografts using the Qiagen RNA micro kit protocol and analysed by Affymetrix U133 plus 2.0 array