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GSE107066
Rattus norvegicus
24 Downloadable Samples
Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
The purpose of this study was to investigate whether paternal high-fat diet (HFD) transgenerationally remodeled the hepatic transcriptome of F2 female rats
Publication Title
Paternal high-fat diet transgenerationally impacts hepatic immunometabolism.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
The purpose of this study was to investigate whether grandpaternal high-fat diet (HFD) transgenerationally remodels the transcriptome of skeletal muscle
Publication Title
Grandpaternal-induced transgenerational dietary reprogramming of the unfolded protein response in skeletal muscle.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 27 Downloadable Samples
- Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
The purpose of this study was to investigate whether paternal high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa to alter metabolism in the F1 and F2 generation offspring
Publication Title
High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Objective: identify novel and relevant aspects of Sorafenib action on liver cancer cells. We found that in rat hepatocholangiocarcinoma (LCSC-2) cells, exposure to the MEK/multikinase inhibitor sorafenib did not inhibit ERK phosphorylation nor induced appreciable cell death in the low micromolar range; instead, the drug elicited a raise of intracellular reactive oxygen species (ROS) accompanied by a severe decrease of oxygen consumption and intracellular ATP levels, all changes consistent with mitochondrial damage. Moreover, Sorafenib induced depolarization of isolated rat liver mitochondria, indicating a possible direct effect on the organelle. Microarray analysis of gene expression in sorafenib-trated cells revealed a metabolic reprogramming toward aerobic glycolysis, that likely accounts for resitance to drug toxicity in this cell line. Importantly, cytotoxicity was strongly potentiated by glucose withdrawal from the culture medium or by the glycolytic inhibitor 2-deoxy-glucose, a finding also confirmed in the highly malignant melanoma cell line B16F10. Mechanistic studies revealed that ROS are pivotal to cell killing by the Sorafenib + 2DG combination, and that a low content of intracellular oxidants is associated with resistance to the drug; instead, Thr172phosphorylation/activation of the AMP-activated protein kinase (AMPK), induced by Sorafenib, may exert protective effects, since cytotoxicity was enhanced by an AMPK specific inhibitor and prevented by the AMPK activator Metformin. Overall, this study identifies novel and relevant aspects of Sorafenib action on liver cancer cells, including mitochondrial damage, induction of ROS and a metabolic cell reprogramming towards glucose addiction, potentially exploitable in therapy.
Publication Title
The multikinase inhibitor Sorafenib enhances glycolysis and synergizes with glycolysis blockade for cancer cell killing.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 57 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Distinct epithelial gene expression phenotypes in childhood respiratory allergy.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Background: In asthma, airway epithelium remodeling can already be detected during childhood, and epithelial cells are more susceptible to virus and oxidative stress. Their exact role in natural history and severity of children allergic respiratory disease remains however surprisingly unexplored.
Publication Title
Distinct epithelial gene expression phenotypes in childhood respiratory allergy.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Background: In asthma, airway epithelium remodeling can already be detected during childhood, and epithelial cells are more susceptible to virus and oxidative stress. Their exact role in natural history and severity of children allergic respiratory disease remains however surprisingly unexplored.
Publication Title
Distinct epithelial gene expression phenotypes in childhood respiratory allergy.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 192 Downloadable Samples
NextSeq 500
Description
Effective therapies for non-small cell lung cancer (NSCLC) remain challenging despite an increasingly comprehensive understanding of somatically altered oncogenic pathways. It is now clear that therapeutic agents with potential to impact the tumor immune microenvironment potentiate immune-orchestrated therapeutic benefit. Herein we evaluated the immunoregulatory properties of histone deacetylase (HDAC) and bromodomain inhibitors, two classes of drugs that modulate the epigenome, with a focus on key cell subsets that are engaged in an immune response. By evaluating human peripheral blood and NSCLC tumors, we show that the selective HDAC6 inhibitor ricolinostat promotes phenotypic changes that support enhanced T cell activation and improved function of antigen presenting cells. The bromodomain inhibitor JQ1 attenuated CD4+Foxp3+ T regulatory cell suppressive function and synergized with ricolinostat to facilitate immune-mediated tumor growth arrest, leading to prolonged survival of mice with lung adenocarcinomas. Collectively, our findings highlight the immunomodulatory effects of two epigenetic modifiers that, together, promote T cell-mediated anti-tumor immunity and demonstrate their therapeutic potential for treatment of NSCLC. Overall design: Single-cell comparison of vehicle (control) and HDAC inhibitor (ricolinostat)-treated tumor infiltrating T cells and macrophages
Publication Title
Synergistic Immunostimulatory Effects and Therapeutic Benefit of Combined Histone Deacetylase and Bromodomain Inhibition in Non-Small Cell Lung Cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We analyzed the role of the histone lysine methyltransferase Set7/9 in the differentiation of human embryonic stem (ES) cells. Human ES cell lines expressing a control short hairpin and a short hairpin against Set7/9 were established and the genome wide expression profile was compared between both cell lines at different days during differentiation. Analysis of both profiles indicates that in the absence of Set7/9 there is a delay in the silencing of self-renewal factors as well as in the induction of differentiation markers. These results indicate that Set7/9 plays an active role in the differentiation of human ES cells.
Publication Title
SETD7 Regulates the Differentiation of Human Embryonic Stem Cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 102 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Inter-patient prostate cancer (PrCa) heterogeneity results in highly variable patient outcomes. Multi-purpose biomarkers to dissect this heterogeneity are urgently required to improve treatment and accelerate drug development in PrCa. Circulating biomarkers are most practical for evaluating this disease. We pursued the analytical validation and clinical qualification of blood mRNA expression arrays.
Publication Title
Prognostic value of blood mRNA expression signatures in castration-resistant prostate cancer: a prospective, two-stage study.
Sample Metadata Fields
Subject
View Samples