Effect of SDHB silencing using siRNA methodologies in the tumor phenotype
Cells silenced for SDHB expression display characteristic features of the tumor phenotype.
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View SamplesSkin squamous cell carcinomas are among the most frequent human cancers. In this study we compared the expression profiles of 10 skin SCCs with a set of 3 normal human epidermis controls.
Multifactorial ERβ and NOTCH1 control of squamous differentiation and cancer.
Disease, Disease stage
View SamplesMedullary breast cancers (MBC) display a basal profile, but a favorable prognosis. We hypothesized that a previously published 368-gene expression signature associated with MBC might serve to define a prognostic classifier in basal cancers. We collected public gene expression and histoclinical data of 2145 invasive early breast adenocarcinomas. We developed a Support Vector Machine (SVM) classifier based on this 368-gene list in a learning set, and tested its predictive performances in an independent validation set. Then, we assessed its prognostic value and that of six prognostic signatures for disease-free survival (DFS) in the remaining 2034 samples. The SVM model accurately classified all MBC samples in the learning and validation sets. A total of 466 cases were basal across other sets. The SVM classifier separated them into two subgroups, subgroup 1 (resembling MBC) and subgroup 2 (not resembling MBC). Subgroup 1 exhibited 71% 5-year DFS, whereas subgroup 2 exhibited 50% (p=9.93E-05). The classifier outperformed the classical prognostic variables in multivariate analysis, conferring lesser risk for relapse in subgroup 1 (HR=0.52, p=3.9E-04). This prognostic value was specific to the basal subtype, in which none of the other prognostic signatures was informative.
A gene expression signature identifies two prognostic subgroups of basal breast cancer.
Age, Specimen part
View SamplesWe recently demonstrated mitochondrial degenerations precede muscle wasting in time course progression of CC. However, the extent of muscle perturbations prior to wasting in CC is unknown. Therefore, we performed global gene expression analysis in CC-induced muscle wasting to enhance understanding of intramuscular perturbations across the development of CC. Overall design: Lewis Lung Carcinoma (LLC) was injected into the hind-flank of C57BL6/J mice at 8 wks age with tumor allowed to develop for 1, 2, 3, or 4 wks and compared to PBS injected control. Muscle wasting was evident at 4 wks LLC. Animals were anesthetized using isoflourane and gastrocnemius muscles were collected for analysis. Conclusions: Current findings present novel evidence of transcriptomic shifts and altered cellular pathways in CC-induced muscle wasting.
Transcriptomic analysis of the development of skeletal muscle atrophy in cancer-cachexia in tumor-bearing mice.
Specimen part, Cell line, Subject
View SamplesThe peroxisome proliferator-activated receptor-coactivator-11 (PGC-11) regulates genes involved in energy metabolism. Increasing adipose tissue energy expenditure through PGC-11 activation has been suggested to be beneficial for systemic metabolism. Pharmacological PGC-11 activators could be valuable tools in the fight against obesity and metabolic disease. Finding such compounds has been challenging partly because PGC-11 is a transcriptional coactivator with no known ligand-binding activities. Importantly, PGC-11 activation is regulated by several mechanisms but protein stabilization is a limiting step as the protein has a short half-life under unstimulated conditions.
Small molecule PGC-1α1 protein stabilizers induce adipocyte Ucp1 expression and uncoupled mitochondrial respiration.
Specimen part
View SamplesPlasmacytoid dendritic cells (pDC) are the major source of type I and type III interferons (IFN-I/III) during viral infections, in response to triggering of endosomal Toll Like Receptors (TLRs) 7 or 9 by viral single-stranded RNA or unmethylated CpG DNA, respectively. Interestingly, this function is restricted to a minor fraction of pDC (Zucchini et al. Int. Immunol. 2008). In this project, we aimed at identifying the molecular pathways involved in inducing IFN-I/III production in this minor faction of pDC during in vivo infection by the mouse cytomegalovirus (MCMV). To achive this goal, we infected with MCMV Ifnb1Eyfp mice, in which IFN-producing pDC can be detected by YFP expression (Scheu et al. PNAS 2008). Thanks to this model, we were able to sort three distinct subsets of pDC: CD86-YFP- (not activated, non IFN-producing), CD86+YFP- (activated, non IFN-producing) and CD86+YFP+ (activated, IFN-producing) and to perform microarray analysis. This allowed us to select genes differentially expressed among these three subsets and to mine these data in order to identify the related signaling pathways.
The activation trajectory of plasmacytoid dendritic cells in vivo during a viral infection.
Specimen part, Treatment
View SamplesGene expression was performed in WT and tumor-bearing (TB) mice to determine the effects of a lung tumor on circadian clock of the liver.
Lung Adenocarcinoma Distally Rewires Hepatic Circadian Homeostasis.
Specimen part, Disease
View SamplesJarid2, a member of the Jumanji family of proteins, is a developmental regulator that is necessary for proper mouse development and stem cell differentiation. To investigate the specific functions of Jarid2 during pancreas development, we generated pancreas-specific Jarid2 mutants.
Late-stage differentiation of embryonic pancreatic β-cells requires Jarid2.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling.
Specimen part
View SamplesTrans fatty acids (tFAs) may have deleterious, long-term transcriptional effects. To explore that issue, we assessed the effects of the tFA elaidic acid and its cis isomer oleic acid on transcription and, in parallel, on DNA methylation.
The trans fatty acid elaidate affects the global DNA methylation profile of cultured cells and in vivo.
Cell line, Treatment
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