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Homo sapiens
63 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Appendiceal cancer patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) often demonstrate an unpredictable variability in survival outcomes. Biomarkers predictive of CRS/HIPEC efficacy could better guide treatment decisions. In this study we hypothesized that variation in the transcriptional programming of appendiceal tumors might distinguish molecular subtypes with differential outcomes after CRS/HIPEC. The goal of this study was to investigate the potential of a prognostic gene signature to discriminate patients with favorable and unfavorable outcomes in a discovery set of patient (the original tumor series (n=24)), and confirm its prognostic value in a second validation series (the validation cohort (n=39)).
Publication Title
Prognostic Molecular Subtypes of Low-Grade Cancer of the Appendix.
Sample Metadata Fields
Sex, Age
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SRP131305- Rattus norvegicus
- 16 Downloadable Samples
Illumina HiSeq 2500
Description
Myosteatosis is the pathological accumulation of lipid that occurs in conjunction with atrophy and fibrosis following skeletal muscle injury or disease. Little is known about the mechanisms by which lipid accumulates in myosteatosis, but many studies have demonstrated the degree of lipid infiltration negatively correlates with muscle function and regeneration. Our goal was to identify biochemical pathways that lead to muscle dysfunction and lipid accumulation in injured rotator cuff muscles, a model that demonstrates severe myosteatosis. Adult rats were subjected to a massive tear to the rotator cuff musculature. After a period of either 0 (healthy control), 10, 30, or 60 days, muscles were prepared for RNA sequencing, shotgun lipidomics, metabolomics, biochemical measures, electron microscopy, and muscle fiber contractility. Following rotator cuff injury, there was a decrease in muscle fiber specific force production that was lowest at 30d. There was a dramatic time dependent increase in triacylglyceride content. Interestingly, genes related to not only triacylglyceride synthesis, but also lipid oxidation were largely downregulated over time. Using bioinformatics techniques, we identified that biochemical pathways related to mitochondrial dysfunction and reactive oxygen species were considerably increased in muscles with myosteatosis. Long chain acyl-carnitines and L-carnitine, precursors to beta-oxidation, were depleted following rotator cuff tear. Electron micrographs showed injured muscles displayed large lipid droplets within mitochondria at early time points, and an accumulation of peripheral segment mitochondria at all time points. Several markers of oxidative stress were elevated following rotator cuff tear. The results from this study suggest that the accumulation of lipid in myosteatosis is not a result of canonical lipid synthesis, but occurs due to decreased lipid oxidation in mitochondria. A failure in lipid utilization by mitochondria would ultimately cause an accumulation of lipid even in the absence of increased synthesis. Further study will identify whether this process is required for the onset of myosteatosis. Overall design: Rats were subjected to a bilateral full-thickness supraspinatus tear and suprascapular neurectomy. Samples (N=4 per group) were taken at 0 days (unoperated controls), 10 days, 30 days, and 60 days post-injury
Publication Title
Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis.
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