Gene expression analysis was conducted to determine changes in gene expression and predict signaling networks in esophageal adenocarcinomas. For this analysis we used 12 EAC samples and 9 normal esophageal tissue samples. The analysis indicated deregulation of a large number of genes. Pathway analysis demonstrated the presence of KRAS signature and predicted activation of multiple transcription networks.
No associated publication
Specimen part
View SamplesThe autonomic nervous system is derived from the neural crest and supplies motor innervation to the smooth muscle of visceral organs, including the lower urinary tract (bladder and urethra, LUT). In rodents, autonomic innervation of the LUT is supplied by the major pelvic ganglia (PG) that lie near the neck of the bladder and proximal urethra. Compared to other autonomic ganglia, the PG are unique in that they harbor both sympathetic and parasympathetic neurons. The coordinated activity of PG neurons is critical for normal functioning of the LUT however, surprisingly little is known about how PG neuronal diversity is established or what molecular factors control PG development. In this study we conducted transcriptome profiling of Sox10-H2BVenus+ sacral neural crest (NC) progenitors to discover candidate genes involved in PG neurogenesis.
No associated publication
Specimen part
View SamplesTo determine the expression of genes in cells following silencing of CDK9 by siRNA.
No associated publication
Specimen part, Cell line
View SamplesNotch-targeted gamma-secretase inhibitors (GSIs) exhibited limited efficacy in glioblastoma patients. We identified that farnesyltransferase inhibitors (FTIs) increased sensitivity to GSIs in glioblastoma stem cells. To interrogate the mechanisms mediating the interaction between these two classes of compounds, we studied the impact on gene expression profiles by the combination of tipifarnib (FTI) and RO4929097 (GSI). We found that this combination treatment significantly suppressed genes implicated cell cycle progression. Real-time PCR validated the activities of tipifarnib to modulate expression of cell cycle regulators. We also showed that RO4929097 sensitized glioblastoma stem cells to compounds targeting some of these cell cycle regulators, such as AURKB and CDK4/6. These results suggest that regulation of cell cycle progression partially mediates the ability of FTIs to sensitize glioblastoma stem cells to GSIs.
No associated publication
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View SamplesNGS from RNA-seq of triple-negative breast cancer cell lines under standard growth conditions were obtained to identify transcriptional features associated with individual triple-negative breast cancer subtypes. All lines identified have been authenticated by short-tandem repeat sequencing and tested to be negative for mycoplasma.
Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies.
Sex, Specimen part, Disease, Cell line
View SamplesOxidative injury and inflammation have been implicated in the genesis of hypertension but the mechanisms involved are not fully understood. We describe a new pathway in which angiotensin II promotes dendritic cell (DC) activation of T cells and ultimately hypertension. NADPH oxidase-dependent superoxide production is increased 5-fold in DCs isolated from hypertensive mice as compared to sham-treated mice. This is associated with DC accumulation of protein-isoketal adducts and production of IL-6, IL-1 and IL-23. DCs from hypertensive mice but not sham mice promote survival and proliferation of CD8+ T cells in culture. Chemically diverse isoketal scavengers not only prevent activation and immunogenicity of DCs, but also attenuate angiotensin II-induced hypertension. Moreover, adaptive transfer of DCs from hypertensive mice prime development of hypertension in response to a subpressor dose of angiotensin II. Exposure of DCs to tert butyl hypdroperoxide promoted isoketal formation, DC stimulation of CD8+ T cell proliferation and primed hypertension in response to low dose angiotensin II. Serum isoprostanes, precursors to isoketals, were found to be elevated in humans with treated hypertension and were markedly elevated in patients with resistant hypertension. These studies show that angiotensin II-induced hypertension activates DCs, in large part by causing superoxide production and formation of isoketals. They define a new mechanism of hypertension and identify a potential new therapeutic approach for this disease.
DC isoketal-modified proteins activate T cells and promote hypertension.
Age, Specimen part
View SamplesVascular smooth muscle cells (VSMCs) are derived from distinct embryonic origins. Vessels originating from differing smooth muscle cell populations have distinct vascular and pathological properties of calcification, atherosclerosis, and structural defects such as aneurysm and coarctation. We hypothesized that domains within a vessel vary in phenotype based on embryonic origin.
No associated publication
Age, Specimen part
View SamplesThe ductus arteriosus (DA) is a fetal vascular shunt that is located between the main pulmonary artery and the aorta. Oxygenated fetal blood from the placenta is shunted past the uninflated fetal lungs, crosses the DA, and is then available to the peripheral organs. In utero closure of the DA is deleterious, but postnatal closure of the DA is necessary for establishment of pulmonary circulation and the transition to newborn life.
Transcriptional profiling reveals ductus arteriosus-specific genes that regulate vascular tone.
Specimen part
View SamplesWe are comparing differential gene expression in WT vs. CENPF knockout hearts
No associated publication
Age, Specimen part
View SamplesVascular smooth muscle cells (VSMCs) are derived from distinct embryonic origins. Vessels originating from differing smooth muscle cell populations have distinct vascular and pathological properties of calcification, atherosclerosis, and structural defects such as aneurysm and coarctation. We hypothesized that domains within a vessel vary in phenotype based on embryonic origin.
No associated publication
Age, Specimen part
View Samples