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GSE26308
Mus musculus, Homo sapiens
24 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
5,6-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.
Publication Title
Dissection of stromal and cancer cell-derived signals in melanoma xenografts before and after treatment with DMXAA.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
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.
Publication Title
A new model for nonalcoholic steatohepatitis in the rat utilizing total enteral nutrition to overfeed a high-polyunsaturated fat diet.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Soy 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.
Publication Title
Mammary gland morphology and gene expression differ in female rats treated with 17β-estradiol or fed soy protein isolate.
Sample Metadata Fields
Sex
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
The 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.
Publication Title
Dietary fat source alters hepatic gene expression profile and determines the type of liver pathology in rats overfed via total enteral nutrition.
Sample Metadata Fields
Sex
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
In 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.
Publication Title
Mammary gland morphology and gene expression signature of weanling male and female rats following exposure to exogenous estradiol.
Sample Metadata Fields
Sex
View Samples- Drosophila melanogaster
- 24 Downloadable Samples
Illumina HiSeq 2500
Description
In order to study the transcriptional response of the fly brain to sugar and complete starvation, we first confirmed that 24 hours of sugar and complete starvation in flies is sufficient to elicit a homeostatic response. Subsequently, we used holidic medium to study effects of deficiency of a specfic macronutrient- cabohydrate in the food. To do so , we generated RNA- seq libraries from brains of 5 day old mated adult male flies maintained on different feeding regimes and used the sequencing data to identify diffrentially expressed genes in the brain under different feeding regimes. Overall design: For each condition, we used RNA prepared from 120-130 manually dissected adult fly brains maintained under complete starvation or sugar starvation regime for 24 hours.
Publication Title
Sugar Promotes Feeding in Flies via the Serine Protease Homolog scarface.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
While 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.
Publication Title
Molecular properties of side population-sorted cells from mouse small intestine.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 1 Downloadable Sample
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We applied genome-wide profiling to successive salt-extracted fractions of micrococcal nuclease-treated Drosophila chromatin. Chromatin fractions extracted with 80mM or 150mM NaCl after digestion contain predominantly mononucleosomes and represent calssical 'active' chromatin. Profiles of these low-salt-soluble fractions display phased nucleosomes over transcriptionally active genes that are locally depleted of histone H3.3 and correspond closely to profiles of RNA polymerase II. Nearly quantitative recovery of chromatin is obtained with 600mM NaCl, however, the remaining insoluble chromatin is enriched in actively transcribed regions. Salt-insoluble chromatin likely represents oligonucleosomes that are attached to large protein complexes. Both low-salt extracted and insoluble chromatin are rich in sequences that correspond to epigenetic regulatory elements genome-wide. The presence of active chromatin at both extremes of salt solubility suggests that these salt fractions capture bound and unbound intermediates in active processes, thus providing a simple, powerful strategy for mapping epigenome dynamics.
Publication Title
Genome-wide profiling of salt fractions maps physical properties of chromatin.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 15 Downloadable Samples
- Affymetrix C. elegans Gene 1.0 ST Array (elegene10st)
Description
Worldwide, more than 1 billion people are affected by infestations with soil-transmitted helminths and also in veterinary medicine helminthiases are a severe thread to livestock due to emerging resistances against the common anthelmintics. Proanthocyanidins have been increasingly investigated for their anthelmintic properties, however, except for an interaction with certain proteins of the nematodes, not much is known about their mode of action. To investigate the anthelmintic activity on a molecular level, a transcriptome analysis was performed in Caenorhabditis elegans after treatment with purified and fully characterized oligomeric procyanidins (OPC). The OPCs had previously been obtained from a hydro-ethanolic (1:1) extract from the leaves of Combretum mucronatum, a plant which is traditionally used in West Africa for the treatment of helminthiasis, therefore, also the crude extract was included in the study. Significant changes in differential gene expression were observed mainly for proteins related to the intestine, many of which were located extracellularly or within cellular membranes. Among the up-regulated genes, several hitherto undescribed orthologues of structural proteins in humans were identified, but also genes that are potentially involved in the worms defense against tannins. For example, T22D1.2, an orthologue of human basic salivary proline-rich protein (PRB) 2, and numr-1 (nuclear localized metal responsive) were found to be strongly up-regulated. Down-regulated genes were mainly associated with lysosomal activity, glycoside hydrolysis or the worms innate immune response. No major differences were found between the groups treated with purified OPCs versus the crude extract. Investigations using GFP reporter gene constructs of T22D1.2 and numr-1 corroborated the intestine as the predominant site of the anthelmintic activity.
Publication Title
Transcriptome analysis reveals molecular anthelmintic effects of procyanidins in C. elegans.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
In this study, we characterize transciprtional phenotypes of airway macrophagages (AMs) throughout homeostatsis, inflammation, and repair at single cell granularity. We confirm that cell origin is the major determinant of AM programing and describe two previously uncharacterized, transcriptionally distinct subdivisions of AMs based on proliferative capacity and inflammatory programing. Overall design: We stimulated mice with LPS and then sampled FACs sorted airway macrophage cells using BAL at Days 0, 3, and 6 and sequenced 1,134 cells from these three groups using RNA-seq
Publication Title
Single cell RNA sequencing identifies unique inflammatory airspace macrophage subsets.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples