This SuperSeries is composed of the SubSeries listed below.
Gene copy number aberrations are associated with survival in histologic subgroups of non-small cell lung cancer.
Specimen part
View SamplesHypothesis: Non-small cell lung cancer (NSCLC) is characterized by a multitude of genetic aberrations with unknown clinical impact. In this study, we aimed to identify gene copy number changes that correlate with clinical outcome in NSCLC. To maximize the chance to identify clinically relevant events, we applied a strategy involving two prognostically extreme patient groups.
Gene copy number aberrations are associated with survival in histologic subgroups of non-small cell lung cancer.
Specimen part
View SamplesThe cerebral cortex underwent a rapid expansion and complexification during recent primate evolution, but the underlying developmental mechanisms remain essentially unknown.
Genes expressed in specific areas of the human fetal cerebral cortex display distinct patterns of evolution.
Age, Specimen part
View SamplesThe delicate interaction between cancer cells and the surrounding stroma plays an essential role in all stages of tumourigenesis. Despite the significance of this interplay, alterations in protein composition underlying tumour-stroma interactions are largely unknown. The aim of this study was to identify stromal proteins with clinical relevance in non-small cell lung cancer.
CD99 is a novel prognostic stromal marker in non-small cell lung cancer.
Specimen part, Subject
View SamplesAnalysis of HeLa cells following depletion of BRCA1 tumor supressor using RNAi against BRCA1. Results provide insight into the molecular mechanisms underlying loss of the BRCA1 function.
BRCA1 represses amphiregulin gene expression.
Treatment
View SamplesReprogramming of mouse fibroblasts toward a myocardial cell fate by forced expression of cardiac transcription factors or microRNAs has recently been demonstrated. The potential clinical applicability of these findings is based on the minimal regenerative potential of the adult human heart and the limited availability of human heart tissue. An initial, but mandatory step toward clinical application of this approach is to establish conditions for conversion of adult human fibroblasts to a cardiac phenotype. Toward this goal, we sought to determine the optimal combination of factors necessary and sufficient for direct myocardial reprogramming of human fibroblasts. Here we show that four human cardiac transcription factors, including Gata4, Hand2, Tbx5, and myocardin, and two microRNAs, miR-1 and miR-133, activated cardiac marker expression in neonatal and adult human fibroblasts. After maintenance in culture for 4-11 weeks, human fibroblasts reprogrammed with these proteins and microRNAs displayed sarcomere-like structures and calcium transients, and a small subset of such cells exhibited spontaneous contractility. These phenotypic changes were accompanied by expression of a broad range of cardiac genes and suppression of non-myocyte genes. These findings indicate that human fibroblasts can be reprogrammed to cardiac-like myocytes by forced expression of cardiac transcription factors with muscle-specific microRNAs and represent a step toward possible therapeutic application of this reprogramming approach.
Reprogramming of human fibroblasts toward a cardiac fate.
Specimen part
View SamplesSaturated fatty acids (SFA) are widely thought to induce inflammation in adipose tissue (AT), while monounsaturated fatty acids (MUFA) are purported to have the opposite effect; however, it is unclear if individual SFA and MUFA behave similarly. Our goal was to examine adipocyte transcriptional networks regulated by individual SFA (palmitic acid, PA; stearic acid, SA) and MUFA (palmitoleic acid, PMA; oleic acid, OA).
Individual saturated and monounsaturated fatty acids trigger distinct transcriptional networks in differentiated 3T3-L1 preadipocytes.
Specimen part
View SamplesWhole blood (paxgene) gene expression was measured using Affymetrix microarray from 377 individuals with rheumatoid arthritis.
Integrative genomic deconvolution of rheumatoid arthritis GWAS loci into gene and cell type associations.
Sex, Age, Specimen part, Disease
View SamplesIn comparing gene expression of normal and CML CD34+ quiescent (G0) and proliferating (G1/S/G2/M) cells, 292 genes were down-regulated and 192 genes were up-regulated in the CML G0 cells. The differentially expressed genes were grouped according to their reported functions and correlations were sought with biological differences previously observed between the same groups. The most apparent correlations include: i) Normal and CML G0 cells are more primitive than G1/S/G2/M cells; ii) CML G0 cells are in a more advanced stage of development and more poised to begin proliferating than normal G0 cells; iii) When CML G0 cells are stimulated to proliferate, they undergo further differentiation and maturation more rapidly than normal G0 cells, but both granulopoiesis and erythropoiesis are less efficient than normal; iv) Whereas normal G0 cells form only granulocyte/monocyte (GM) colonies when stimulated by cytokines, CML G0 cells consistently form a combination of GM and erythroid clusters and colonies; and v) Prominin-1 (CD133) is the gene most down-regulated in CML G0 cells and its down-regulation appears to be associated with the spontaneous formation of erythroid colonies by CML progenitors without EPO. The gene most over-expressed in CML G0 cells is LepR, but its role in contributing to the myeloid expansion and other abnormalities is unknown. It was hoped that LepR might serve as a therapeutic target, but leptin had no stimulatory or inhibitory effect on either normal or CML G0 cells, our attempts to make a specific LepR antibody were unsuccessful, and no other potentially targetable over-expressed surface antigens were identified.
Gene Expression Differences between Enriched Normal and Chronic Myelogenous Leukemia Quiescent Stem/Progenitor Cells and Correlations with Biological Abnormalities.
Specimen part, Disease, Disease stage
View SamplesTo identify metastasis suppressor genes, which are functionally compromised in late-stage breast cancer, we compared the gene expression profiles of an established breast cancer progression cell line model and leveraged large amounts of publically available data by applying multiple bioinformatics filters. Here we report the identification of serum deprivation response (SDPR, also known as cavin-2) as a bona fide metastasis suppressor, capable of impairing the metastatic growth of cancer cells while having no effect on the growth of primary tumors.
SDPR functions as a metastasis suppressor in breast cancer by promoting apoptosis.
Disease, Disease stage, Cell line
View Samples