Most commonly used models of non-alcoholic steatohepatitis (NASH) are diets based on specific gene knockouts or represent extreme manipulations of diet. We have examined the effects of modest increased caloric intake and high dietary unsaturated fat content on the development of NASH in male rats using a model in which overfeeding is accomplished via intragastric infusion of liquid diets as a part of total enteral nutrition. Male Sprague dawley rats were fed diets 5% corn oil containing diets at 187 Kcal/kg3/4/d or fed 70% corn oil containing diets at 220 Kcal/kg3/4/d for a period of 3 weeks. Hepatic gene expression were assessed at the end of the study. Our results indicate that overfeeding of high unsaturated fat diets leads to pathological, endocrine and metabolic changes characteristic of NASH patients and is associated with increased oxidative stress and TNF-a.
A new model for nonalcoholic steatohepatitis in the rat utilizing total enteral nutrition to overfeed a high-polyunsaturated fat diet.
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View SamplesSoy foods have been suggested to have both positive health benefits and potentially adverse effects largely as a result of their content of isoflavone phytoestrogens. Since soy protein isolate (SPI) contains isoflavones, in addition to purported health benefits, safety concerns have been raised regarding the use of SPI and soy formulas, because of potential estrogenic actions during the neonatal period, including the potential for reproductive toxicity, infertility, and the possibility of increased risk for development and recurrence of estrogen sensitive cancers such as breast cancer. In the current study, we used a rat model to compare the effects of SPI with those of 17b-estradiol (E2), on global gene expression profiles and morphology in the female rat mammary gland. Rats were either fed AIN-93G diets containing casein (CAS) or SPI beginning on postnatal day (PND) 30.
Mammary gland morphology and gene expression differ in female rats treated with 17β-estradiol or fed soy protein isolate.
Sex
View SamplesWhile the existence of intestinal epithelial stem cells (IESCs) has been well established, their study has been limited due to the inability to isolate them. Previous work has utilized side population (SP) sorting of the murine small intestinal mucosa to isolate a viable fraction of cells enriched for putative IESCs. We have used microarray analyses to characterize the molecular features of this potential stem cell population.
Molecular properties of side population-sorted cells from mouse small intestine.
No sample metadata fields
View SamplesThe current study was designed to determine if dietary fatty acid concentration and composition affects the development and progression of nonalcoholic fatty liver disease. Male SD rats were overfed diets low (5%) or high (70%) fat diets via total enteral nutrition where the fat source was olive oil (monounsaturated), or corn oil (polyunsaturated). Overfeeding 5% corn oil produced little steatosis relative to feeding 5% olive oil. This was associated with lower fatty acid synthesis and reduced SREBP-c signaling in the 5% corn oil group. Overfeeding 70% fat diets increased steatosis and lead to increased liver necrosis in the 70% corn oil but not olive oil group. Increased injury after feeding polyunsaturated fat diets was linked to peroxidizability of hepatic free fatty acids and triglycerides and appearance of peroxidaized lipid products HETES and HODES previously linked to clinical nonalcoholic steatohepatitis.
Dietary fat source alters hepatic gene expression profile and determines the type of liver pathology in rats overfed via total enteral nutrition.
Sex
View SamplesIn order to properly understand whether xenoestrogens act as estrogens, it is essential to possess a solid portrait of the physiological effects of exogenous estradiol. Because the estrogen-dependent gene expression is one of the primary biomarkers of estrogenic action, we have assessed effects of three doses of exogenous estradiol (0.1, 1.0 and 10 g/kg of body weight/day) on the mammary gland morphology and gene expression profiles by microarray analysis of prepubertal male and female rats of both sexes compared to untreated controls. Estradiol was administered subcutaneously with minipumps from weaning at PND21 to the end of the experiment at PND33. The data suggest that the male mammary is a sensitive tissue for estrogenicity assessment.
Mammary gland morphology and gene expression signature of weanling male and female rats following exposure to exogenous estradiol.
Sex
View SamplesHyperactivation of phosphatidylinositol-3 kinase (PI3K) promotes escape from hormone dependence in estrogen receptor-positive breast cancer.
Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer.
Specimen part, Cell line
View SamplesAnalysis of 104 breast cancer biopsies (removed prior to any treatment with tamoxifen or chemotherapeutic agents) from patients aged between 31 years and 89 years at the time of diagnosis (mean age = 58 years). Twenty were less than 50 years and seventy-seven women were 50 years, or older, at diagnosis. The size of the tumours ranged between 0.6 cm and 8.0 cm (mean = 2.79 cm). Eighteen tumours were T1 (<2 cm) in maximal dimension; 83 were T2 (25 cm) and 3 tumours were T3 (>5 cm). Eighty-two were invasive ductal carcinoma, 17 were invasive lobular and five were tumours of special type (two tubular and three mucinous). Eleven tumours were grade 1; 40 were grade 2; and 53 were grade 3. Sixty-seven tumours were oestrogen receptor (ER) positive and 34 were ER negative (ER status was determined by Enzyme Immuno-Assay (EIA); a positive result was defined as more than 200 fmol/g protein). ER status was not available for 3 patients. Forty-five tumours had no axillary metastases and 59 tumours had metastasised to axillary lymph nodes. Sixty-nine women were treated with post-operative tamoxifen; 26 did not receive tamoxifen. Fifty patients were treated with adjuvant systemic chemotherapy (CMF +/ adriamycin); 45 patients did not receive chemotherapy. Details regarding tamoxifen and systemic chemotherapy were not available for 9 patients. Maximal follow-up was 3,026 days with a mean follow-up of 1,887 days.
Correlating transcriptional networks to breast cancer survival: a large-scale coexpression analysis.
Age, Specimen part, Disease stage
View SamplesThe estrogen receptor-alpha (ER) determines breast cancer cell phenotype and is a prognostic indicator. A better understanding of the mechanisms controlling ER function may uncover improved strategies for the treatment of breast cancer. Proteasome inhibition was previously reported to regulate estrogen-induced transcription but the mechanisms by which it influences ER function remain controversial. In this study we investigated the transcriptome-wide effects of the proteasome inhibitor Velcade on estrogen-regulated transcription in MCF7 human breast cancer cells and demonstrate a specific global decrease in estrogen-induced transcription.
Estrogen-dependent gene transcription in human breast cancer cells relies upon proteasome-dependent monoubiquitination of histone H2B.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide transcriptome profiling of homologous recombination DNA repair.
Specimen part, Cell line
View SamplesHomologous recombination-mediated DNA repair deficiency (HRD) predisposes to cancer development, but also provides therapeutic opportunities. Here, we identified an HRD gene signature that robustly predicted HRD status. Unexpectedly, concurrent loss of PTEN in BRCA1-deficient cells might extensively rewire the HR repair network and confer resistance to PARP inhibitor, partially through over-expression of TTK. We used the HRD gene signature as a drug discovery tool and found several PARP-inhibitor-synergizing agents through the connectivity map. Thus gene expression profiling can be used to define the functional status of the HR repair network providing prognostic and therapeutic information.
Genome-wide transcriptome profiling of homologous recombination DNA repair.
Specimen part, Cell line
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