mRNA expression in colon cancer tumores
Mice that express human interleukin-8 have increased mobilization of immature myeloid cells, which exacerbates inflammation and accelerates colon carcinogenesis.
Sex, Specimen part
View SamplesThe gene expression of murine splenic myeloid derived suppressor cells treated with Tff2 is characterized. The motivation of the study originates in the fact that Gr1+Cd11b+ myeloid-derived suppressor cells (MDSCs), which resemble immature myeloid cells (IMCs), expand during cancer in response to inflammatory cytokines and accumulate in the spleen. MDSCs promote neoplastic progression through their suppression of anti-tumourigenic cytotoxic T-cells. MDSCs are also rapidly expanded following acute insults, but in cancer as opposed to acute inflammation, MDSCs persist. It is now recognized that a vagally-mediated, anti-inflammatory reflex arc promoting acetylcholine secretion by Cd4+ (Cd44hiSelllo) T cells, is necessary for a return to homeostasis after an acute insult. Failure of this restorative neural circuit might contribute to unabated procarcinogenic inflammation, with the chronic expansion of MDSCs driving carcinogenesis. Trefoil factor 2 (Tff2) is a secreted anti-inflammatory peptide produced by both epithelial cells and a small subset of splenic T cell.
Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer.
Sex, Age, Specimen part
View SamplesWe performed gene expression profiling of hydrogen-bond surrogate that targets hypoxia-inducible transcription factior complex and results in inhibition of hypoxia-inducible genes with relatively minimal perturbation of non-targeted signaling pathways.
Protein domain mimetics as in vivo modulators of hypoxia-inducible factor signaling.
Cell line, Treatment
View SamplesWe performed gene expression profiling of alveolar macrophages from mice that were intratracheally instilled with saline or bleomycin. We identified a number of differentially expressed genes in the two groups of cells. Overall design: Expression profiling of alveolar macrophages from mice that were intratracheally instilled with saline or bleomycin.
Metabolic characterization and RNA profiling reveal glycolytic dependence of profibrotic phenotype of alveolar macrophages in lung fibrosis.
Specimen part, Disease, Disease stage, Cell line, Subject
View SamplesWe used microarrays to detail transcriptional changes in cultured human smooth muscle cells in response to acute and chronic 2-methoxyestradiol treatment
2-Methoxyestradiol blocks the RhoA/ROCK1 pathway in human aortic smooth muscle cells.
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View SamplesPreconditioning with a small dose of endotoxin confers unparalleled protection against otherwise lethal models of sepsis. The mechanisms of preconditioning have been investigated extensively in isolated immune cells such as macrophages. However, the role of tissue in mediating the protective response to preconditioning remains unknown. Using the kidney as a model organ, we identify the essential role of the renal epithelial cell in mediating the full expression of protective preconditioning. The protective phenotype is characterized by the clustering of macrophages around S1 segments of proximal tubules, which forms a functional unit mediating protection. To investigate the molecular pathways, we laser microdissected S1 segments from the following: 1) Non-preconditioned mice subjected to single-dose 5 mg/kg lipopolysaccharide (0111:B4, LPS) intraperitoneally for 24 hours. 2) Preconditioned mice subjected to 0.25 mg/kg LPS followed 24 hour later by 5 mg/kg LPS (LPS/LPS). 3) Control mice (saline vehicle).
Endotoxin Preconditioning Reprograms S1 Tubules and Macrophages to Protect the Kidney.
Sex, Specimen part, Treatment, Time
View SamplesTo facilitate a better understanding of the molecular heterogeneity of breast cancer and to uncover gene-survival associations that segregate with distinct molecular subtypes, we recently compiled a meta-analytical database of over 2,000 human breast tumor expression profiles variously annotated for clinical and pathological variables and derived from various institutions worldwide. This database was utilized for the breast tumor study cited below: Nagalla, et. al., Genome Biology, 2013. While the majority of the tumor expression profiles included in this database derived from publicly accessible microarray repositories, a number of the samples had not been previously published. Here, we describe the origin of these samples and provide their associated clinical and pathological annotations with the hope that other investigators will be able to utilize these data in their own research.
Interactions between immunity, proliferation and molecular subtype in breast cancer prognosis.
Age, Disease stage
View SamplesGermline BRCA1 or BRCA2 mutations (mtBRCA1 and mtBRCA2) dramatically increase risk for high-grade serous ovarian cancer (HGSOC), the most commonly diagnosed histotype. Other risk factors for this cancer, which originates primarily in the distal fallopian tube epithelium (FTE), implicate ovulation. To test whether mtBRCA1 or mtBRCA2 FTE cells respond differently to peri-ovulatory follicular fluid (FF) exposure than control patient FTE, gene expression profiles from primary FTE cultures were compared at baseline, 24h after FF exposure, and 24h after FF replacement with culture medium. Hierarchical clustering revealed both FF exposure and BRCA mutation status affect gene expression, with BRCA1 mutation having the greatest impact. Analysis revealed increased NFB and EGFR signaling at baseline, with increased interferon signaling after recovery from FF exposure in mtBRCA1 samples. Inhibition of EGFR signaling and ISGylation by increased BRCA1 expression was verified in an immortalized FTE cell line, OE-E6/E7, stably transfected with BRCA1. Suppression of ISG15 and ISGylated protein levels by BRCA1 expression was found to be mediated by decreased NFB signaling and was transiently suppressed by FF exposure. This study demonstrates increased NFB signaling associated with decreased BRCA1 expression resulting in increased ISG15 and ISGylation following FF exposure, which could represent potential targets for chemoprevention.
BRCA1 Mutation Status and Follicular Fluid Exposure Alters NFκB Signaling and ISGylation in Human Fallopian Tube Epithelial Cells.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The nuclear bile acid receptor FXR is a PKA- and FOXA2-sensitive activator of fasting hepatic gluconeogenesis.
Sex, Specimen part, Treatment
View SamplesIdentified genes deregulated in mouse primary hepatocytes after modulation of expression/activity of FOXA2 and FXR in glucagon or insulin state
The nuclear bile acid receptor FXR is a PKA- and FOXA2-sensitive activator of fasting hepatic gluconeogenesis.
Sex, Specimen part, Treatment
View Samples