NCI-60 cancer cell lines were profiled with their genome-wide gene expression patterns using Affymetrix HG-U133A chips.
A strategy for predicting the chemosensitivity of human cancers and its application to drug discovery.
No sample metadata fields
View SamplesThe objective of this study was to investigate the link between signaling-network activation and transcriptional regulation downstream of tumor necrosis factor (TNF), epidermal growth factor (EGF), and insulin.
No associated publication
Cell line, Treatment
View SamplesAdding lysolecithin to feed has reportedly improved the performance of broiler chickens. Lysolecithin is generated by phospholipase catalyzed hydrolysis of lecithin. The enzymatic reaction converts phospholipids into lysophospholipids, with lysophosphatidylcholine (LPC) the primary product. Here we compared supplementation with a commercial lysolecithin (Lysoforte(R) Kemin Industries, Inc., Des Moines, IA) with comparable levels of purified LPC for effects on broilers. Despite no differences in weight gain during the starter period, we discovered a significant increase in average villus length in the jejunum with lysolecithin, but not with LPC. High-throughput gene expression microarray analyses revealed many more genes were regulated in the epithelium of jejunum by lysolecithin compared to LPC. The most upregulated genes and pathways were for collagen, extracellular matrix and integrins. Staining sections of jejunum with Sirius Red confirmed the increased deposition of collagen fibrils in villi of broilers fed lysolecithin but not LPC. Thus, lysolecithin elicits gene expression in the intestinal epithelium leading to enhanced collagen deposition and villus length. LPC alone as a supplement does not mimic these responses. Feed supplementation with lysolecithin triggers changes in the intestinal epithelium with the potential to improve overall gut health and performance.
No associated publication
Specimen part, Treatment
View SamplesThis project describes the establishment and validation of a murine orthotopic xenograft model using fresh human tumor samples that recapitulates the critical components of human pancreatic adenocarcinoma. The authors discuss the proven and theoretical advantages of the model as well as future translational implications.
Clinical, molecular and genetic validation of a murine orthotopic xenograft model of pancreatic adenocarcinoma using fresh human specimens.
Specimen part, Cell line
View SamplesWe developed a novel network inference approach, Biologically Anchored Knowledge Expansion (BAKE), to analyze large volume gene expression data obtained from a mouse model of insulin resistance progression.
No associated publication
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epigenetic coordination of signaling pathways during the epithelial-mesenchymal transition.
Cell line
View SamplesPancreatic ductal adenocarcinoma (PDAC) is a deadly disease with limited effective treatment options. PDAC tumors frequently harbor the constitutively activated form of KRAS which drives proliferative signaling, but directly targeting KRAS has so far been unsuccessful. To overcome this limitation, combinatorial treatment strategies have been developed to inhibit upstream activators and downstream effectors of KRAS signaling. One such combination using trametinib, a MEK1/2 inhibitor, and lapatinib, an EGFR/HER2 inhibitor, substantially reduced tumor growth in a patient-derived xenograft (PDX) model of PDAC. Although trametinib and lapatinib are both known to inhibit the canonical MAPK signaling cascade, the effects of this combination on other important pathways in pancreatic cancer remains unclear. To investigate this, we analyze global gene expression profiles from PDX models of PDAC treated with trametinib, lapatinib, or their combination. Our results show that trametinib induces similar yet less significant expression changes compared to combination while lapatinib has little to no effect as a monotherapy in the acute treatment setting. In the chronic treatment setting, we show that tumors exposured to prolonged treatment with trametinib plus lapatinib eventually leads to adapative resistance. Expression analyses of resistant tumors revealed concominant gene expression changes in upstream receptor tyrosine kinases (RTKs).
No associated publication
No sample metadata fields
View SamplesHistone acetyltransferases (HATs) and deacetylases (HDACs) function antagonistically to control histone acetylation. As acetylation is a histone mark for active transcription, HATs have been associated with active and HDACs with inactive genes. We describe here genome-wide mapping of HATs and HDACs binding on chromatin and nd that both are found at active genes with acetylated histones. Our data provide evidence that HATs and HDACs are both targeted to transcribed regions of active genes by phosphorylated RNA Pol II. Furthermore, the majority of HDACs in the human genome function to reset chromatin by removing acetylation at active genes. Inactive genes that are primed by MLL-mediated histone H3K4 methylation are subject to a dynamic cycle of acetylation and deacetylation by transient HAT/HDAC binding, preventing Pol II from binding to these genes but poising them for future activation. Silent genes without any H3K4 methylation signal show no evidence of being bound by HDACs.
Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes.
Specimen part, Treatment
View Samples40 bladder cancer cell lines were profiled with their genome-wide gene expression patterns using Affymetrix HG-U133A chips.
A strategy for predicting the chemosensitivity of human cancers and its application to drug discovery.
No sample metadata fields
View SamplesToxin A (TcdA) and Toxin B (TcdB), of the pathogen Clostridium difficile, are virulence factors that cause gross pathologic changes (e.g. inflammation, secretion, and diarrhea) in the infected host, yet the molecular and cellular pathways leading to observed host responses are poorly understood. To address this gap, TcdA and/or TcdB were injected into the ceca of mice and the genome-wide transcriptional response of epithelial layer cells was examined. Bioinformatic analysis of gene expression identified sets of cooperatively expressed genes. Further analysis of inflammation associated genes revealed dynamic chemokine responses.
In vivo physiological and transcriptional profiling reveals host responses to Clostridium difficile toxin A and toxin B.
No sample metadata fields
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