Acute effects caused by the non-genotoxic carcinogen and peroxisome proliferator (PP) diethylhexylphthalate (DEHP) in the mouse liver
Gene ontology mapping as an unbiased method for identifying molecular pathways and processes affected by toxicant exposure: application to acute effects caused by the rodent non-genotoxic carcinogen diethylhexylphthalate.
Sex, Specimen part, Compound, Time
View SamplesCigarette smoke (CS) is one of risk factor to chronic obstructive pulmonary disease that is the major causes of death in the world. Furthermore, CS is an independent risk factor for chronic kidney disease (CKD) in the general adult population. The goal of this project was to identified the mechanisms of renal damage that might be associated with exposure to CS extract (CSE) in human kidney proximal tubular epithelial cell line (HK-2 cells) cells. Overall design: RNA sequencing of human kidney proximal tubular epithelial cell line (HK-2 cells) after 24 hours exposure to 0.6% CSE.
Cigarette Smoke Exposure Increases Glucose-6-phosphate Dehydrogenase, Autophagy, Fibrosis, and Senescence in Kidney Cells In Vitro and In Vivo.
Specimen part, Treatment, Subject
View SamplesMamamlian cardiogenesis occurs through the development of discreate populations of first and second heart field progenitors. We have used a dual transgenic color reproter system to isolate purified populations of these progenitors.
Generation of functional ventricular heart muscle from mouse ventricular progenitor cells.
No sample metadata fields
View SamplesPrevious reports have defined three subsets of mouse NK cells on the basis of the expression of CD27 and CD11b. The developmental relationship between these subsets was unclear. To address this issue, we evaluated the overall proximity between mouse NK cell subsets defined by CD27 and CD11b expression using pangenomic gene expression profiling. The results suggest that CD27+CD11b-, CD27+CD11b+ and CD27-CD11b+ correspond to three different intermediates stages of NK cell development.
Maturation of mouse NK cells is a 4-stage developmental program.
No sample metadata fields
View SamplesCancer metastasis is a fetal problem that claims life of over 90% of cancer patients. It is hypothesized that cancer stem cells (CSCs) mediate cancer metastasis and such cells are often resistant to chemotherapy. Studying BRCA1 associated cancers, we found that CSCs form fillopodia and protrusions enriching for active forms of ezrin/radixin/moesin proteins and they have a much higher potential to metastasize than non-CSCs. Microarray analysis indicated that many pathways related to cell adhesion, extracellular matrix and cytoskeleton were differentially regulated in CSCs. Although inhibition of cytoskeleton remodeling by cisplatin treatment retarded CSC motility and cancer metastasis, drug resistant cancers eventually emerge containing markedly increased number of CSCs. This event is at least partially attributed to the activation of PI3K/mTOR signaling, and can be significantly inhibited by the treatment of rapamycin. These results provide strong evidence that cytoskeletal rearrangement and PI3K/mTOR signaling play a distinct role in mediating CSC mobility and viability, and blocking of both pathways in CSCs synergistically inhibits primary and metastatic cancer growth in BRCA1 associated tumors.
Synergistic therapeutic effect of cisplatin and phosphatidylinositol 3-kinase (PI3K) inhibitors in cancer growth and metastasis of Brca1 mutant tumors.
Specimen part
View SamplesTo identify the target genes of Evi-1 in hematopoietic stem cells (HSCs), we carried out genome-wide transcriptional analysis using wild-type and Evi-1-deleted HSCs.
Evi-1 is a critical regulator for hematopoietic stem cells and transformed leukemic cells.
Sex, Age
View Samples[1] Lactic acidosis time course: MCF7 cells were exposed to lactic acidosis for different length of time. We used microarrays to examine the genomic programs of cells incubated under lactic acidosis for different length of time
Lactic acidosis triggers starvation response with paradoxical induction of TXNIP through MondoA.
Cell line, Treatment
View SamplesExpression profiling of normal NIH3T3 and transformed NIH3T3 K-ras cell lines grown for 72 hours in optimal glucose availability (25 mM glucose) or low glucose availability (1 mM). Low glucose induces apoptosis in transformed cells as compared to normal ones.
Oncogenic K-Ras decouples glucose and glutamine metabolism to support cancer cell growth.
Cell line, Time
View Samples5,6-Dimethylxanthenone-4-acetic acid (DMXAA), a tumor vascular disrupting agent, is shown here to have substantial activity as a single agent against human A375 melanoma xenografts in nude mice (94 % hemorrhagic necrosis after 24 h, and 26 days growth delay following single dose at 25 mg/kg). CD45+ cells in tumor tissue increased 5-fold over the first 3 days after treatment, which was due largely to an influx of CD11b+ Ly6G+ neutrophils. Using murine and human multiplex cytokine assays to dissect the cytokines produced by host stromal cells or by the melanoma cells, it was shown that both the stromal cells and the A375 melanoma cells produced cytokines capable of attracting neutrophils into the tumor. The same xenografts were also analyzed using human and mouse Affymetrix microarrays to separately identify tumor cell-specific (human) and stromal cell-specific (mouse) gene expression changes. DMXAA induced numerous stromal cytokine mRNAs, including IP-10, IL-6, MIP-1/, MIP-2, KC, RANTES, MIG, MCP-1 and IL-1, many of which were also elevated at the protein level. Numerous human cytokine mRNAs were also induced including MCP-1, IL-8, GRO, VEGF, GM-CSF and IL-6, which again was in line with our protein data. Pathway analysis indicated that significant numbers of the stromal mRNAs induced by DMXAA are regulated downstream of TNF-, interferon- and NFB. Our results suggest that DMXAA may have utility in combination therapy for human melanoma through the activation of pro-inflammatory signalling pathways and cytokine expression from both stromal and tumor cells, leading to haemorrhagic necrosis, neutrophil influx and growth inhibition.
Dissection of stromal and cancer cell-derived signals in melanoma xenografts before and after treatment with DMXAA.
Specimen part, Cell line
View SamplesPrimordial genomic challenge compromises embryonic development and survival, and surveillance of deployed transcriptional programs may provide an early opportunity to forecast phenotype abnormalities. Here, comparisons between wild-type and calreticulin-ablated embryonic stem cells revealed transcriptome shifts precipitated by calreticulin loss. Bioinformatic analysis identified down and up-regulation in 1187 and 418 genes, respectively. Cardiovascular development precedes other organogenic programs, and examination of cardiogenic genes revealed a map of calreticulin-calibrated expression profiles that encompass the developmental regulators, Ccnd1, Ccnd2 and Notch1. Interrogation of primary function in the resolved network forecasted abnormalities during myocardial development. Whole embryo magnetic resonance imaging, verified by pathoanatomical analysis, diagnosed prominent ventricular septal defect. Correlation clustering and network resolution of probesets associated with protein folding/chaperoning and calcium handling demonstrated 14 and 19 genes, respectively, modulated by calreticulin deficiency. Calreticulin deletion provoked ontological re-prioritization of gene expression, molecular transport and protein trafficking that translated into multiple subcellular functional outcomes. Individual stem cell-derived cardiomyocytes lacking calreticulin demonstrated a disorganized contractile apparatus with mitochondrial paucity and architectural aberrations. Thus, bioinformatic deconvolution of primordial embryonic stem cell transcriptomes enables predictive phenotyping of defective developmental networks that coalesce from complex systems biology hierarchies.
Decoded calreticulin-deficient embryonic stem cell transcriptome resolves latent cardiophenotype.
No sample metadata fields
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