Hepatocellular carcinoma (HCC) is the second most common cause of cancer related death. NAFLD affects a large proportion of the US population. Its incidence and prevalence are increasing to epidemic proportions around the world and is known to increase the risk of HCC. We studied how intrahepatic lipids affect adaptive immunity and HCC development in different murine models of NASH and HCC. Linoleic acid, a fatty acid found in NAFLD caused a selective loss of hepatic CD4+ but not CD8+ T cells leading to accelerated hepatocarcinogenesis. CD4+ T cells were more dependent on oxidative phosphorylation for energy source than CD8+ T cells, and disruption of oxidative phosphorylation by linoleic acid caused more severe damage in CD4+ T cells leading to selective loss of these cells. In vivo blockade of ROS using n-acetylcysteine reversed the NASH-induced hepatic CD4+ T cell decrease and delayed NASH-promoted HCC. Our results provide a new link between lipid metabolism and impaired anti-tumor surveillance.
NAFLD causes selective CD4(+) T lymphocyte loss and promotes hepatocarcinogenesis.
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View SamplesPompe disease is a genetic disorder resulting from a deficiency of lysosomal acid alpha-glucosidase (GAA) that manifests as a clinical spectrum with regard to symptom severity and rate of progression. In this study, we used microarrays to examine gene expression from the muscle of two cohorts of infantile-onset Pompe patients to identify transcriptional differences that may contribute to the disease phenotype. We found strong similarities among the gene expression profiles generated from biceps and quadriceps, and identified a number of signaling pathways altered in both cohorts. We also found that infantile-onset Pompe patient muscle had a gene expression pattern characteristic of immature or regenerating muscle, and exhibited many transcriptional markers of inflammation, despite having few overt signs of inflammatory infiltrate. Further, we identified genes exhibiting correlation between expression at baseline and response to therapy. This combined dataset can serve as a foundation for biological discovery and biomarker development to improve the treatment of Pompe disease.
Transcriptional response to GAA deficiency (Pompe disease) in infantile-onset patients.
Sex, Specimen part, Disease, Treatment, Subject
View SamplesInfluence of STIM1 on the transcriptome of CD4+ T cell subsets
STIM1 controls T cell-mediated immune regulation and inflammation in chronic infection.
Treatment
View SamplesmRNA expression profiling of pancreatic cancer, comparing adjacent normal tissue, patient tumour and first generation patient derived xenograft tumours
Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging.
Sex, Age
View SamplesAging is associated with major nuclear changes affecting genomic integrity and gene expression. Here we compare the gene expression profiles in the neocortex of young (5 months old) and old (30 months old) B6xC3 F1 mice.
SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging.
Sex, Age
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