Gene Expression Profiling of a Mouse Xenograft Model of Triple-Negative Breast Cancer Brain Metastases With and Without Vorinostat Treatment.
Vorinostat inhibits brain metastatic colonization in a model of triple-negative breast cancer and induces DNA double-strand breaks.
Treatment
View SamplesThe polyphenol resveratrol has anti-inflammatory effects in various cells, tissues, animals and human settings of low-grade inflammation. Psoriasis is a disease of both localized and systemic low-grade inflammation. The Sirtuin1 enzyme thought to mediate the effects of resveratrol is present in skin and resveratrol is known to downregulate NF-B; a major contributor in the development of psoriasis. Consequently we investigated whether resveratrol has an effect on an Imiquimod induced psoriasis-like skin inflammation in mice and sought to identify candidate genes, pathways and interleukins mediating the observed effects. The study consisted of three treatment groups: A control group, an Imiquimod group and an Imiquimod+resveratrol group. Psoriasis severity was assessed using elements of the Psoriasis Area Severity Index, actual skin thickness measurements, and histological examination. We performed an RNA microarray from lesional skin and afterwards Ingenuity pathway analysis to identify affected signalling pathways. Our microarray was compared to a previously deposited microarray to determine if gene changes were psoriasis-like, and to a human microarray to determine if findings could be relevant in a human setting. Imiquimod treatment induced a psoriasis-like skin inflammation. Resveratrol significantly diminished the severity of the psoriasis-like skin inflammation. The RNA microarray revealed a psoriasis-like gene expression-profile in the Imiquimod treated group, and highlighted several resveratrol dependent changes in relevant genes, such as increased expression of genes associated with retinoic acid stimulation and reduced expression of genes involved in IL-17 dependent pathways (e.g.IL-17A, IL-17F,IL-23p19 ). Quantitative PCR confirmed a resveratrol dependent decrease in mRNA levels of IL-17A and IL-19; both central in developing psoriasis. In conclusion, resveratrol ameliorates psoriasis, and changes in expression of retinoic acid stimulated genes, IL-17 signalling pathways, IL-17A and IL-19 mRNA levels in a beneficial manner suggests it might have a role in the treatment of psoriasis and should be explored further in a human setting.
Resveratrol ameliorates imiquimod-induced psoriasis-like skin inflammation in mice.
Specimen part
View SamplesStudies have shown that vitamin D can enhance glucose-stimulated insulin secretion (GSIS) and change the expression of genes in pancreatic β-cells. Still the mechanisms linking vitamin D and GSIS are unknown.
Vitamin D metabolites influence expression of genes concerning cellular viability and function in insulin producing β-cells (INS1E).
Specimen part, Cell line, Treatment
View SamplesWe construced combinations of genetic deletions to infer genetic interactions in genomic expression data.
Prediction of phenotype and gene expression for combinations of mutations.
No sample metadata fields
View SamplesPurpose: A 128-gene signature has been proposed to predict poor outcomes in patients with stage II and III colorectal cancer. In the present study we aimed to validate this previously published 128-gene signature on external and independent data from patients with stage II and III colon cancer.
Gene expression profiles in stages II and III colon cancers: application of a 128-gene signature.
Sex, Age, Disease stage, Race
View SamplesObservational studies from low-income countries have shown that the vaccination against diphtheria, tetanus and pertussis (DTP) is associated with excess female mortality due to infectious diseases. To investigate possible changes in gene expression after DTP vaccination, we identified a group of nine comparable West African girls, from a biobank of 356 children, who were due to receive DTP booster vaccine at age 18 months. We extracted RNA from blood samples before, and 6 weeks after, vaccination to analyse the coding transcriptome in leukocytes using expression microarrays, and ended up with information from eight girls. The data was further analysed using dedicated array pathway and network software. We aimed to study whether DTP vaccination introduced a systematic alteration in the immune system in girls. We found very few transcripts to alter systematically. Those that did mainly belonged to the interferon (IFN) signalling pathway. We scrutinized this pathway as well as the interleukin pathways. Two out of eight showed a down-regulated IFN pathway and two showed an up-regulated IFN pathway. The two with down-regulated IFN pathway had also down-regulated IL-6 pathway. In the study of networks, two of the girls stood out as not having the inflammatory response as top altered network. In conclusion, the transcriptome changes following DTP booster vaccination were subtle, but it is possible to identify sub groups that deviate from each other, mainly in the IFN response.
Leukocyte transcript alterations in West-African girls following a booster vaccination with diphtheria-tetanus-pertussis vaccine.
Sex, Age, Specimen part
View SamplesWe have looked for fusion genes in ovarian carcinomas. We combined previously known genomic aberrations, detected by karyotyping, and gene expression analysis. We found recurrent DPP9 gene expression deregulation with matching translocations. In additon, candidate fusion partner genes from the exon-level expression analysis were ranked according to deviating expression compared to the median of the sample set. The results were collated with data obtained from the RNA-seq analysis.
Involvement of DPP9 in gene fusions in serous ovarian carcinoma.
Specimen part
View SamplesTo compare the transcriptome profiles of the two principal histological variants of malignant germ cell tumor that occur in childhood
Pediatric malignant germ cell tumors show characteristic transcriptome profiles.
No sample metadata fields
View SamplesExisting controversy regarding the importance of AMP-activated protein kinase (AMPK) in fatty acid (FA) oxidation in skeletal muscle with contraction/exercise may to some extent pertain to redundant AMPK1 signaling. Using a mouse model lacking both AMPK1 and -2 in skeletal muscle specifically (mdKO) we hypothesized that FA utilization would be impaired in skeletal muscle. Calorimetric analysis showed a similar respiratory exchange ratio (RER) of AMPK WT and mdKO mice when fed normal chow, a high fat diet or with prolonged fasting. Though, in vivo treadmill exercise at the same relative intensity induced a higher RER in mdKO mice compared to WT (WT=0.81; mdKO=0.87; p<0.01) indicating a decreased utilization of FA. Ex vivo incubation of soleus muscle revealed that basal and contraction-induced FA oxidation was impaired in mdKO mice, suggesting that the increased RER during in vivo running exercise originated from decreased skeletal muscle FA oxidation. A decreased muscle protein expression of CD36 and FABPpm (by 17-40%) together with abolishment of TBC1D1 Ser237 phosphorylation in mdKO mice, may result in lower FA transport capacity and FA transport protein translocation to sarcolemma, respectively. In summary this study shows that the catalytically active AMPK subunits are required for normal stimulation of FA utilization during exercise and contractions.
AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice.
Specimen part
View SamplesIn a randomized controlled dietary intervention study we compared an isocaloric Healthy Nordic diet with the average Nordic diet for influence on peripheral blood mononuclear cells (PBMC) gene expression. We studied obese adults with features of the metabolic syndrom, n=66. There was no significant difference in age, BMI, or gene expression between the groups before the intervention. The intervention lasted for 18-24 weeks.
Effects of a healthy Nordic diet on gene expression changes in peripheral blood mononuclear cells in response to an oral glucose tolerance test in subjects with metabolic syndrome: a SYSDIET sub-study.
Age, Time
View Samples