Expression data for MCF7 cells treated with 34 different chemicals
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Jay Tiesman
PROVIDER: E-GEOD-69845 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:This study provides an evaluation of changes in gene expression associated with treating human HepaRG cells with 34 different chemical compounds. Gene expression experiments studies were performed in triplicate (n=3) with the cells for each replicate treated and harvested on separate days. This series is part of a SuperSeries in which human toxicology-relevant cell lines were treated with three doses of 34 chemical compounds (and corresponding vehicle controls) for 6 hours. Each compound/vehicle treatment group was an individual study performed at different times. Each study was analyzed separately and themes common between studies were reported.
2016-03-28 | E-GEOD-69844 | biostudies-arrayexpress
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2016-03-28 | E-GEOD-69850 | biostudies-arrayexpress
Project description:This study provides an evaluation of changes in gene expression associated with treating human Ishikawa cells with 34 different chemical compounds. Gene expression experiments studies were performed in triplicate (n=3) with the cells for each replicate treated and harvested on separate days. This series is part of a SuperSeries in which human toxicology-relevant cell lines were treated with three doses of 34 chemical compounds (and corresponding vehicle controls) for 6 hours. Each compound/vehicle treatment group was an individual study performed at different times. Each study was analyzed separately and themes common between studies were reported.
2016-03-28 | E-GEOD-69849 | biostudies-arrayexpress
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2016-03-25 | E-GEOD-69851 | biostudies-arrayexpress
Project description:Introduction: Renal ischemia-reperfusion (IR) causes acute kidney injury (AKI) with high mortality and morbidity. The objective of this study was to ameliorate kidney IR injury and identify novel biomarkers for kidney injury and repair. Methods: Left renal ischemia was induced in rats by clamping renal artery for 45 minutes, followed by reperfusion and right nephrectomy. Thirty minutes prior to ischemia, rats (n=8/group) received Valproic Acid (150 mg/kg; VPA), Dexamethasone (3 mg/kg; Dex) or Vehicle (Saline) intraperitoneally. Animals were sacrificed at 3h, 24h or 120h post- IR and blood, urine and kidney were collected. Results: Serum creatinine (mg/dL) at 24 h IR in VPA (2.7±1.8) and Dex (2.3±1.2) was reduced (P<0.05) compared to Vehicle (3.8±0.5). At 3h post-IR, urine albumin (mg/ml) was higher in Vehicle (1.47±0.10), VPA (0.84±0.62) and Dex (1.04±0.73) compared to uninjured/untreated control (0.14±0.26) group. At 24h post-IR urine Lipocalin-2 (µg/ml) was significantly higher (P<0.05) in VPA, Dex and Vehicle groups (9.61-11.36) compared to uninjured/untreated control (0.67±o.29); also, Kidney Injury Molecule-1 (KIM-1; ng/ml) was significantly higher in VPA, Dex and Vehicle groups (13.7-18.7) compared uninjured/untreated control (1.7±1.9). KIM-1 levels were significantly (P<0.05) higher in all groups compared to uninjured/untreated control levels. Histopathology at 3h post IR demonstrated (P<0.05) reduction in ischemic injury in the renal cortex in VPA (Grade 1.6± 1.5) compared to Vehicle (Grade 2.9±1.1) group. Inflammatory cytokines IL1β and IL6 were down-regulated in VPA and Dex groups. BCL2 was higher in VPA group. DNA microarray analysis demonstrated reduced stress response and injury, and improved recovery related gene expression in the kidneys of VPA treated animals. Conclusions: VPA administration reduced kidney IR injury and improved regeneration. KIM-1 and Lipocalin-2 appear to be promising early urine biomarkers of acute ischemic kidney injury. We had three experimental groups. Group A, VPA treatment; Group B, Dexamethasone treatment; and Group C, No treatment (vehicle saline control). Treatments were administered prior to the induction of left renal ischemia. Animals underwent 45 minutes of left renal ischemia, followed by reperfusion, and right nephrectomy as described above. Following reperfusion, animals were sacrificed at 3, 24 or 120 hours (n=8/group). In the 3 hour group, rats were maintained under anesthesia after surgery until sacrifice. In the 24 and 120 hour groups, the rats were recovered and returned to the cages for normal housing. Analgesic buprenorphine (0.05mg/kg) was administered every 12 h for three days post-operatively. After animal sacrifice, urine, blood, and kidney were collected for kidney functional biomarker assays, histology and / or molecular analyses. Urine was obtained via cystocentesis and blood was obtained via the left renal vein. Tissue and urine samples collected from normal (naïve) animals (n=5) were used for baseline measurements. A subset of 46 animals (n = 4-5 per group) were selected for microarray analysis.
2015-07-06 | E-GEOD-58438 | biostudies-arrayexpress
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2015-03-01 | E-GEOD-60769 | biostudies-arrayexpress
Project description:Analysis of Diffuse Large B-Cell Lymphoma (DLBCL) OCI-LY3 cell line treated with 14 different known drugs at 2 different concentrations and profiled at 6, 12 and 24 hrs after treatment. We used this gene expression data to design a challenge where participants were required to develop methods to predict activity of compound pairs using gene expression profile following single compound treatment, drug response curve of each compound and baseline genetic profile of OCI-LY3 cell line. GeneChip HT HG-U219 array plates were used to analyze gene expression changes induced by treatment with 14 drug compounds in OCI-Ly3 cells at 6, 12 and 24h. 3 replicates were analyxed for each drug/time combination. Vehicle (DMSO)-treated control samples were used for comparison with each replicate. Altogether 282 samples were analyzed in this study.
2014-09-25 | E-GEOD-51068 | biostudies-arrayexpress
Project description:Although drug induced steatosis represents a mild type of hepatotoxicity, it can progress into more severe non-alcoholic steatohepatitis. Current models used for safety assessment in drug development and chemical risk assessment do not accurately predict steatosis in humans. Therefore, new models need to be developed to screen compounds for steatogenic properties. We have studied the usefulness of mouse precision-cut liver slices (PCLS) as an alternative to animal testing to gain more insight into the mechanisms involved in the steatogenesis. To this end, PCLS were incubated 24h with the model steatogenic compounds, amiodarone (AMI), valproic acid (VA), and tetracycline (TET). Transcriptome analysis using DNA microarrays was used to identify genes and processes affected by these compounds. AMI and VA upregulated lipid metabolism, whereas processes associated with extracellular matrix remodelling and inflammation were downregulated. TET downregulated mitochondrial functions, lipid metabolism, and fibrosis. From the transcriptomics data it was hypothesized that all 3 compounds affect peroxisome proliferator activated-receptor (PPAR) signalling. Application of PPAR reporter assays classified AMI and VA as PPARγ and triple PPARα/ (β/δ)/γ agonist, respectively, whereas TET had no effect on any of the PPARs. Some of the differentially expressed genes were considered as potential candidate biomarkers to identify PPAR agonists (i.e. AMI and VA) or compounds impairing mitochondrial functions (i.e. TET). Finally, comparison of our findings with publicly available transcriptomics data showed that a number of processes altered in the mouse PCLS was also affected in mouse livers and human primary hepatocytes exposed to known PPAR agonists. Thus mouse PCLS are a valuable model to identify mechanisms of action of compounds altering lipid metabolism. Two sets of candidate biomarkers could be used to screen compounds interfering with lipid metabolism by different mechanisms. Steatogenic compounds exposures Mouse precision cut liver slices (PCLS) were prepared from livers obtained from 5 different C57BL/6 male mice (24 weeks old). PCLS were cultured for 24 hours at 80% of oxygen; 5% CO2 and the remaining gas volume was filled up to 95% with N2. PCLS were exposed to model steatogenic, cholestatic, and necrotic compounds selected based on published reports. As steatogenic model compounds amiodarone (AMI), valproic acid (VA), and tetracycline (TET) were selected. As model cholestatic compounds cyclosporin A (CsA), chlorpromazine (CPZ), and ethinyl estradiol (EE) were applied. As necrotic compounds acetaminophen (APAP), isoniazid (ISND), and paraquat (PQ) were applied. To select a non-toxic dose eventually to be used for exposure experiments and subsequent gene expression profiling experiments, the following concentrations ranges were tested: AMI 0-100 μM, VA 0-500 μM, TET 0-100 μM , CsA 0-100 μM, CPZ 0-80 μM, EE 0-100 μM, PQ 0-10 μM, APAP 0-3000 μM and ISND 0-1000 μM. CsA, CPZ, AMI, PQ, EE were dissolved in DMSO, VA and TET were dissolved in ethanol (EtOH), and ISND was dissolved in PBS. The compounds were added to the culture medium at a final concentration of 0.1% vol/vol in an appropriate solvent (DMSO, EtOH, or PBS). Slices incubated with the solvents at 0.1% vol/vol served as controls. The viability of the slices was assessed by measuring the ATP content normalized on protein. Dose selection for the three steatogenic, cholestatic, and necrotic exposures were performed in 5 independent experiments with slices obtained from 5 mice. Concentrations that did not cause a decrease of the ATP level normalized on protein, compared to controls, were selected. For transcriptome analysis, PCLS were cultured at the same conditions as described above. The selected concentrations for steatogenic, cholestatic, and necrotic drugs were tested again in liver slices obtained from 5 different mice to re-confirm that the selected concentrations for the exposure experiments were not toxic. The concentrations used in the exposure experiments were for the steatogenic compounds: 50 μM for AMI, 200 μM for VA, and 40 μM for TET. For the cholestatic exposures 40 μM CsA, 20 μM CPZ, and 10 μM EE. For the necrotic compounds: 1000 μM APAP, 1000 μM ISND, and 5 μM PQ. Thereafter, RNA was extracted from three slices per each condition and after processing, the samples were hybridized on the HT Mouse Genome 430 PM array plate(s) using the Affymetrix GeneTitan system (CA, USA).
2013-12-23 | E-GEOD-51543 | biostudies-arrayexpress
Project description:Although drug induced steatosis represents a mild type of hepatotoxicity, it can progress into more severe non-alcoholic steatohepatitis. Current models used for safety assessment in drug development and chemical risk assessment do not accurately predict steatosis in humans. Therefore, new models need to be developed to screen compounds for steatogenic properties. We have studied the usefulness of mouse precision-cut liver slices (PCLS) as an alternative to animal testing to gain more insight into the mechanisms involved in the steatogenesis. To this end, PCLS were incubated 24h with the model steatogenic compounds, amiodarone (AMI), valproic acid (VA), and tetracycline (TET). Transcriptome analysis using DNA microarrays was used to identify genes and processes affected by these compounds. AMI and VA upregulated lipid metabolism, whereas processes associated with extracellular matrix remodelling and inflammation were downregulated. TET downregulated mitochondrial functions, lipid metabolism, and fibrosis. From the transcriptomics data it was hypothesized that all 3 compounds affect peroxisome proliferator activated-receptor (PPAR) signalling. Application of PPAR reporter assays classified AMI and VA as PPARγ and triple PPARα/ (β/δ)/γ agonist, respectively, whereas TET had no effect on any of the PPARs. Some of the differentially expressed genes were considered as potential candidate biomarkers to identify PPAR agonists (i.e. AMI and VA) or compounds impairing mitochondrial functions (i.e. TET). Finally, comparison of our findings with publicly available transcriptomics data showed that a number of processes altered in the mouse PCLS was also affected in mouse livers and human primary hepatocytes exposed to known PPAR agonists. Thus mouse PCLS are a valuable model to identify mechanisms of action of compounds altering lipid metabolism. Two sets of candidate biomarkers could be used to screen compounds interfering with lipid metabolism by different mechanisms. Cholestatic compounds exposures Mouse precision cut liver slices (PCLS) were prepared from livers obtained from 5 different C57BL/6 male mice (24 weeks old). PCLS were cultured for 24 hours at 80% of oxygen; 5% CO2 and the remaining gas volume was filled up to 95% with N2. PCLS were exposed to model steatogenic, cholestatic, and necrotic compounds selected based on published reports. As steatogenic model compounds amiodarone (AMI), valproic acid (VA), and tetracycline (TET) were selected. As model cholestatic compounds cyclosporin A (CsA), chlorpromazine (CPZ), and ethinyl estradiol (EE) were applied. As necrotic compounds acetaminophen (APAP), isoniazid (ISND), and paraquat (PQ) were applied. To select a non-toxic dose eventually to be used for exposure experiments and subsequent gene expression profiling experiments, the following concentrations ranges were tested: AMI 0-100 μM, VA 0-500 μM, TET 0-100 μM , CsA 0-100 μM, CPZ 0-80 μM, EE 0-100 μM, PQ 0-10 μM, APAP 0-3000 μM and ISND 0-1000 μM. CsA, CPZ, AMI, PQ, EE were dissolved in DMSO, VA and TET were dissolved in ethanol (EtOH), and ISND was dissolved in PBS. The compounds were added to the culture medium at a final concentration of 0.1% vol/vol in an appropriate solvent (DMSO, EtOH, or PBS). Slices incubated with the solvents at 0.1% vol/vol served as controls. The viability of the slices was assessed by measuring the ATP content normalized on protein. Dose selection for the three steatogenic, cholestatic, and necrotic exposures were performed in 5 independent experiments with slices obtained from 5 mice. Concentrations that did not cause a decrease of the ATP level normalized on protein, compared to controls, were selected. For transcriptome analysis, PCLS were cultured at the same conditions as described above. The selected concentrations for steatogenic, cholestatic, and necrotic drugs were tested again in liver slices obtained from 5 different mice to re-confirm that the selected concentrations for the exposure experiments were not toxic. The concentrations used in the exposure experiments were for the steatogenic compounds: 50 μM for AMI, 200 μM for VA, and 40 μM for TET. For the cholestatic exposures 40 μM CsA, 20 μM CPZ, and 10 μM EE. For the necrotic compounds: 1000 μM APAP, 1000 μM ISND, and 5 μM PQ. Thereafter, RNA was extracted from three slices per each condition and after processing, the samples were hybridized on the HT Mouse Genome 430 PM array plate(s) using the Affymetrix GeneTitan system (CA, USA).
2013-12-23 | E-GEOD-51544 | biostudies-arrayexpress
Project description:Although drug induced steatosis represents a mild type of hepatotoxicity, it can progress into more severe non-alcoholic steatohepatitis. Current models used for safety assessment in drug development and chemical risk assessment do not accurately predict steatosis in humans. Therefore, new models need to be developed to screen compounds for steatogenic properties. We have studied the usefulness of mouse precision-cut liver slices (PCLS) as an alternative to animal testing to gain more insight into the mechanisms involved in the steatogenesis. To this end, PCLS were incubated 24h with the model steatogenic compounds, amiodarone (AMI), valproic acid (VA), and tetracycline (TET). Transcriptome analysis using DNA microarrays was used to identify genes and processes affected by these compounds. AMI and VA upregulated lipid metabolism, whereas processes associated with extracellular matrix remodelling and inflammation were downregulated. TET downregulated mitochondrial functions, lipid metabolism, and fibrosis. From the transcriptomics data it was hypothesized that all 3 compounds affect peroxisome proliferator activated-receptor (PPAR) signalling. Application of PPAR reporter assays classified AMI and VA as PPARγ and triple PPARα/ (β/δ)/γ agonist, respectively, whereas TET had no effect on any of the PPARs. Some of the differentially expressed genes were considered as potential candidate biomarkers to identify PPAR agonists (i.e. AMI and VA) or compounds impairing mitochondrial functions (i.e. TET). Finally, comparison of our findings with publicly available transcriptomics data showed that a number of processes altered in the mouse PCLS was also affected in mouse livers and human primary hepatocytes exposed to known PPAR agonists. Thus mouse PCLS are a valuable model to identify mechanisms of action of compounds altering lipid metabolism. Two sets of candidate biomarkers could be used to screen compounds interfering with lipid metabolism by different mechanisms. Necrotic compounds exposures Mouse precision cut liver slices (PCLS) were prepared from livers obtained from 5 different C57BL/6 male mice (24 weeks old). PCLS were cultured for 24 hours at 80% of oxygen; 5% CO2 and the remaining gas volume was filled up to 95% with N2. PCLS were exposed to model steatogenic, cholestatic, and necrotic compounds selected based on published reports. As steatogenic model compounds amiodarone (AMI), valproic acid (VA), and tetracycline (TET) were selected. As model cholestatic compounds cyclosporin A (CsA), chlorpromazine (CPZ), and ethinyl estradiol (EE) were applied. As necrotic compounds acetaminophen (APAP), isoniazid (ISND), and paraquat (PQ) were applied. To select a non-toxic dose eventually to be used for exposure experiments and subsequent gene expression profiling experiments, the following concentrations ranges were tested: AMI 0-100 μM, VA 0-500 μM, TET 0-100 μM , CsA 0-100 μM, CPZ 0-80 μM, EE 0-100 μM, PQ 0-10 μM, APAP 0-3000 μM and ISND 0-1000 μM. CsA, CPZ, AMI, PQ, EE were dissolved in DMSO, VA and TET were dissolved in ethanol (EtOH), and ISND was dissolved in PBS. The compounds were added to the culture medium at a final concentration of 0.1% vol/vol in an appropriate solvent (DMSO, EtOH, or PBS). Slices incubated with the solvents at 0.1% vol/vol served as controls. The viability of the slices was assessed by measuring the ATP content normalized on protein. Dose selection for the three steatogenic, cholestatic, and necrotic exposures were performed in 5 independent experiments with slices obtained from 5 mice. Concentrations that did not cause a decrease of the ATP level normalized on protein, compared to controls, were selected. For transcriptome analysis, PCLS were cultured at the same conditions as described above. The selected concentrations for steatogenic, cholestatic, and necrotic drugs were tested again in liver slices obtained from 5 different mice to re-confirm that the selected concentrations for the exposure experiments were not toxic. The concentrations used in the exposure experiments were for the steatogenic compounds: 50 μM for AMI, 200 μM for VA, and 40 μM for TET. For the cholestatic exposures 40 μM CsA, 20 μM CPZ, and 10 μM EE. For the necrotic compounds: 1000 μM APAP, 1000 μM ISND, and 5 μM PQ. Thereafter, RNA was extracted from three slices per each condition and after processing, the samples were hybridized on the HT Mouse Genome 430 PM array plate(s) using the Affymetrix GeneTitan system (CA, USA).
2013-12-23 | E-GEOD-51542 | biostudies-arrayexpress