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.
A toxicogenomic approach for the prediction of murine hepatocarcinogenesis using ensemble feature selection.
Sex, Specimen part, Treatment, Time
View SamplesRat has been treated with different compounds with the purpose of investigating toxicological mechanisms. But toxic and non-toxic compounds has been administered. 3 toxic (ANIT, DMN, NMF) 3 non-tox (Caerulein, dinitrophenol(DNP), Rosiglitazone) in 5-plicates (30 arrays in all) and 9 untreated (control), 39 samples in all.
Integration of clinical chemistry, expression, and metabolite data leads to better toxicological class separation.
No sample metadata fields
View SamplesWe profiled the skeletal muscle transcriptome between wild type and aB-crystallin/HspB2 knock mice exposed to normal chow and high fat diets to examine the role of aB-crystallin/HspB2 in diet induced obesity. Combined with metabolic profiling of the mice, these data reveal that aB-crystallin/HspB2 is involved in the genesis of insulin resistance on a high fat diet, and we provide extensive RNA profiling to illuminate potential mechanistic insights into the muscle-specific role of aB-crystallin/HspB2. Overall design: Hind limb muscle mRNA profiles of wild type and aB-crystallin/HspB2 knock mice exposed to either normal chow or high fat diets using RNAseq analysis
αB-crystallin and HspB2 deficiency is protective from diet-induced glucose intolerance.
No sample metadata fields
View SamplesPurpose: To identify transcriptional changes by RNA-seq in tumor samples, before bevacizumab combination treatment and after bevacizumab combination treatment in both responding and non-responding recurrent glioblastoma patients Overall design: Three comparison analyses were further performed: 1.) Paired analysis of pre- and post-treated samples from responding patients; 2.) Comparison of pre-treated samples of responders vs. non-responders; 3.) Paired analysis of pre- and post-treated samples from non-responding patients The sample ''characteristics: batch'' represents a combination of the RNA-extraction date and the library-preparation date for each sample.
Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients.
Sex, Disease, Disease stage, Subject, Time
View SamplesFNDC4 is a novel secreted factor sharing high homology with the exercise-associated myokine irisin (FNDC5). Here we report that Fndc4 is robustly upregulated in various mouse models of inflammation as well as in human inflammatory conditions. Specifically, subjects with inflammatory bowel disease show increased FNDC4 levels locally at inflamed sites of the intestine. Interestingly, administration of recombinant FNDC4 during colitis development in mice resulted in markedly reduced disease severity compared to mice injected with a control protein. Conversely, mice that lacked Fndc4 showed increased colitis severity. Analysis of binding of FNDC4 to different immune cell types revealed strong and specific binding to macrophages and monocytes. FNDC4 treatment of bone marrow-derived macrophages in vitro resulted in reduced phagocytosis, improved survival and reduced pro-inflammatory chemokine expression. Hence, treatment with FNDC4 resulted in a state of dampened macrophage activity, while enhancing their survival. Thus, we have characterized a novel factor with direct therapeutic potential in inflammatory bowel disease and possibly other inflammatory diseases.
FNDC4 acts as an anti-inflammatory factor on macrophages and improves colitis in mice.
Sex, Specimen part, Treatment
View SamplesIn the intestine, Hedgehog (Hh) signalling orchestrates epithelial homeostasis in a bidirectional loop. Differentiated enterocytes secrete the ligand leading to active downstream signaling exclusively in the stroma. In turn, Hh-driven stromal factors contribute to the control of intestinal stem cell numbers and induce epithelial differentiation.
Stromal Hedgehog signalling is downregulated in colon cancer and its restoration restrains tumour growth.
Sex, Specimen part
View SamplesLgr6-positive cells have been shown to label stem/progenitors cells in several tissues including tongue and skin. However their role in mammary gland has never been investigated. Here we used Lgr6-eGFP-IRES-CreER2 mice to isolate and characterize Lgr6-positive population in mammary gland of 5-week old female mice. Overall design: Examination of transcriptional differences between Lgr6 positive and negative cells
Lgr6 labels a rare population of mammary gland progenitor cells that are able to originate luminal mammary tumours.
Sex, Specimen part, Subject
View Samplesconsequences of astrocytes on GSCs, gene expression profiles generated from glioblastoma stem-like cells grown alone (mono-culture) and compared to those generated 48h after the initiation of co-culture with astrocytes
Coculture with astrocytes reduces the radiosensitivity of glioblastoma stem-like cells and identifies additional targets for radiosensitization.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Induction of hepatocellular carcinoma by in vivo gene targeting.
Age, Specimen part
View SamplesThe distinct phenotypic and prognostic subclasses of human hepatocellular carcinoma (HCC) are difficult to reproduce in animal experiments. Here we have used in vivo gene targeting to insert an enhancer-promoter element at an imprinted chromosome 12 locus in mice, thereby converting ~1 in 20,000 normal hepatocytes into a focus of HCC with a single genetic modification. A 300 kb chromosomal domain containing multiple mRNAs, snoRNAs and microRNAs was activated surrounding the integration site. An identical domain was activated at the syntenic locus in a specific molecular subclass of spontaneous human HCCs with a similar histological phenotype, which was associated with partial loss of DNA methylation. These findings demonstrate the accuracy of in vivo gene targeting in modeling human cancer, and suggest future applications in studying various tumors in diverse animal species. In addition, similar insertion events produced by randomly integrating vectors could be a concern for liver-directed human gene therapy.
Induction of hepatocellular carcinoma by in vivo gene targeting.
Age
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