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GSE68387
Mus musculus, Homo sapiens, Rattus norvegicus
1938 Downloadable Samples
Affymetrix Rat Gene 2.0 ST Array (ragene20st), Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2), Affymetrix Rat Expression 230A Array (rae230a), Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm), Affymetrix Rat Genome 230 2.0 Array (rat2302), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Subject, Time
View Samples- Homo sapiens
- 659 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PDX tumors at various passages post first implantation in nude mice
Publication Title
High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 449 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Rat Expression 230A Array (rae230a)
Description
Assessing the carcinogenic potential of drug candidates is a costly procedure which requires the life-long treatment of rodents at different dose levels. A promising approach, which may to a certain degree reduce the need for animal studies in the future is toxicogenomics. The idea is to employ microarray platforms for the genome-wide expression profiling of compounds, which may facilitate the discovery of biomarker genes and provide insights in molecular mechanisms.
Publication Title
A toxicogenomic approach for the prediction of murine hepatocarcinogenesis using ensemble feature selection.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Rattus norvegicus
- 418 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
The carcinogenic potential of chemicals is currently evaluated with rodent life-time bioassays, which are time consuming, and expensive with respect to cost, number of animals and amount of compound required. Since the results of these 2-year bioassays are not known until quite late during development of new chemical entities, and since the short-term test battery to test for genotoxicity, a characteristic of genotoxic carcinogens, is hampered by low specificity, the identification of early biomarkers for carcinogenicity would be a big step forward. Using gene expression profiles from the livers of rats treated up to 14 days with genotoxic and non-genotoxic carcinogens we previously identified characteristic gene expression profiles for these two groups of carcinogens. We have now added expression profiles from further hepatocarcinogens and from non-carcinogens the latter serving as control profiles. We used these profiles to extract biomarkers discriminating genotoxic from non-genotoxic carcinogens and to calculate classifiers based on the support vector machine (SVM) algorithm. These classifiers then predicted a set of independent validation compound profiles with up to 88% accuracy, depending on the marker gene set. We would like to present this study as proof of the concept that a classification of carcinogens based on short-term studies may be feasible.
Publication Title
Cross-platform toxicogenomics for the prediction of non-genotoxic hepatocarcinogenesis in rat.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 345 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Rat Expression 230A Array (rae230a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Phenobarbital induces cell cycle transcriptional responses in mouse liver humanized for constitutive androstane and pregnane x receptors.
Sample Metadata Fields
Age, Specimen part, Treatment, Subject, Time
View Samples- Homo sapiens
- 222 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene expression profile in circulating leukocytes identifies patients with coronary artery disease
Publication Title
Gene expression patterns in peripheral blood correlate with the extent of coronary artery disease.
Sample Metadata Fields
Sex, Age, Specimen part, Race
View Samples- Rattus norvegicus
- 63 Downloadable Samples
Affymetrix Rat Expression 230A Array (rae230a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cross-platform toxicogenomics for the prediction of non-genotoxic hepatocarcinogenesis in rat.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 167 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcino- genesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARKO -PXRKO ), double humanized CAR and PXR (CARh - PXRh), and wild-type C57BL/6 mice. Wild-type and CARh-PXRh mouse livers exhibited temporally and quantitatively similar tran- scriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were ob- served with peak expression occurring between 1 and 7 days PB ex- posure. All these transcriptional responses were absent in CARKO- PXRKO mouse livers and largely reversible in wild-type and CARh - PXRh mouse livers following 91 days of PB exposure and a subse- quent 4-week recovery period. Furthermore, PB-mediated upregu- lation of the noncoding RNA Meg3, which has recently been associ- ated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARh-PXRh mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.
Publication Title
Phenobarbital induces cell cycle transcriptional responses in mouse liver humanized for constitutive androstane and pregnane x receptors.
Sample Metadata Fields
Age, Specimen part, Treatment, Subject, Time
View Samples- Rattus norvegicus
- 119 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st), Affymetrix Rat Expression 230A Array (rae230a)
Description
The carcinogenic potential of chemicals is currently evaluated with rodent life-time bioassays, which are time consuming, and expensive with respect to cost, number of animals and amount of compound required. For insight into early mechanisms of non-genotoxoc carcinogenesis and for identification of potential early biomarkers of non-genotoxic carcinogenesis, groups of rats were treated with a range of known non-genotoxic carcinogens for a period of 14, 28, or 90 days, and liver tissue was harvested for expression profiling. Control groups were treated with appropriate vehicles.
Publication Title
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 40 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples