Experiment design
Glucose-dependent cell size is regulated by a G protein-coupled receptor system in yeast Saccharomyces cerevisiae.
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View SamplesThe purpose of the present study was to investigate the association of glutathione S-transferase P1 (GSTP1) expression with resistance to neoadjuvant paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (P-FEC) in human breast cancers. The relationship of GSTP1 expression and GSTP1 promoter hypermethylation with intrinsic subtypes was also investigated. In this study, primary breast cancer patients (n = 123, stage II-III) treated with neoadjuvant P-FEC were analyzed. Tumor samples were obtained by vacuum-assisted core biopsy before P-FEC. GSTP1 expression was determined using immunohistochemistry, GSTP1 promoter methylation index (MI) using bisulfite methylation assay and intrinsic subtypes using DNA microarray. The pathological complete response (pCR) rate was significantly higher in GSTP1-negative tumors (80.0%) than GSTP1-positive tumors (30.6%) (P = 0.009) among estrogen receptor (ER)-negative tumors but not among ER-positive tumors (P = 0.267). Multivariate analysis showed that GSTP1 was the only predictive factor for pCR (P = 0.013) among ER-negative tumors. Luminal A, luminal B and HER2-enriched tumors showed a significantly lower GSTP1 positivity than basal-like tumors (P = 0.002, P < 0.001 and P = 0.009, respectively), while luminal A, luminal B and HER2-enriched tumors showed a higher GSTP1 MI than basal-like tumors (P = 0.076, P < 0.001 and P < 0.001, respectively). In conclusion, these results suggest the possibility that GSTP1 expression can predict pathological response to P-FEC in ER-negative tumors but not in ER-positive tumors. Additionally, GSTP1 promoter hypermethylation might be implicated more importantly in the pathogenesis of luminal A, luminal B and HER2-enriched tumors than basal-like tumors.
GSTP1 expression predicts poor pathological complete response to neoadjuvant chemotherapy in ER-negative breast cancer.
Age, Specimen part, Disease stage
View SamplesWe analyzed the effects of cellular context on the function of the synovial sarcoma-specific fusion protein, SS18-SSX, using human pluripotent stem cells containing the drug-inducible SS18-SSX gene. To investigate the cell-type-dependent effecfts of SS18-SSX, we performed gene expression profiling experiments.
SS18-SSX, the Oncogenic Fusion Protein in Synovial Sarcoma, Is a Cellular Context-Dependent Epigenetic Modifier.
Specimen part
View SamplesTo identify genes regulated by complex of NF90 and nuclear factor 45 (NF45) in hepatocellular carcinoma, we performed comprehensive analyses of mRNA expression in Huh7 cells depleted of NF90.
Suppression of MicroRNA-7 (miR-7) Biogenesis by Nuclear Factor 90-Nuclear Factor 45 Complex (NF90-NF45) Controls Cell Proliferation in Hepatocellular Carcinoma.
Cell line
View SamplesIn order to better understand chondrodysplasia disease mechanisms, we induced hypertrophic chondrocytes from chondrodysplasia-specific iPSCs and analyzed their gene expression profile.
Differentiation of Hypertrophic Chondrocytes from Human iPSCs for the In Vitro Modeling of Chondrodysplasias.
Specimen part
View SamplesIn cytotoxic T cells (CTL), Protein Kinase B /Akt is activated by the T cell antigen receptor (TCR) and the cytokine Interleukin 2 (IL2), in part by phosophorylation of Akt by Phospholipid dependent kinase 1 (PDK1).
Protein kinase B controls transcriptional programs that direct cytotoxic T cell fate but is dispensable for T cell metabolism.
Specimen part
View SamplesThe extent to which carbon flux is directed towards fermentation vs. respiration differs between cell types and environmental conditions. Understanding the basic cellular processes governing carbon flux is challenged by the complexity of the metabolic and regulatory networks. To reveal the genetic basis for natural diversity in channeling carbon flux, we applied Quantitative Trait Loci analysis by phenotyping and genotyping hundreds of individual F2 segregants of budding yeast that differ in their capacity to ferment the pentose sugar xylulose. Causal alleles were mapped to the RXT3 and PHO23 genes, two components of the large Rpd3 histone deacetylation complex. We show that these allelic variants modulate the expression of SNF1/AMPK-dependent respiratory genes. Our results suggest that over close evolutionary distances, diversification of carbon flow is driven by changes in global regulators, rather than adaptation of specific metabolic nodes. Such regulators may improve the ability to direct metabolic fluxes for biotechnological applications. Overall design: mRNA profiles of S. cerevisiae strain BY4741 with either the RXT3 or PHO23 genes either deleted, replaced by S. cerevisiae T73 allele or replaced by S. cerevisiae PHO23 allele
Natural Diversity in Pentose Fermentation Is Explained by Variations in Histone Deacetylases.
Cell line, Subject
View SamplesCells constantly adapt to changes in their environment. In the majority of cases, the environment shifts between conditions that were previously encountered during the course of evolution, thus enabling evolutionary-programmed responses. In rare cases, however, cells may encounter a new environment to which a novel response is required. To characterize the first steps in adaptation to a novel condition, we studied budding yeast growth on xylulose, a sugar that is very rarely found in the wild. We previously reported that growth on xylulose induces the expression of amino-acid biosynthesis genes, in multiple natural yeast isolates. This induction occurs despite the presence of amino acids in the growth medium and is a unique response to xylulose, not triggered by any of the naturally available carbon sources tested. Propagating these strains for ~300 generations on xylulose significantly improved their growth rate. Notably, the most significant change in gene expression was the loss of amino acid biosynthesis gene induction. Furthermore, the reduction in amino-acid biosynthesis gene expression on xylulose was strongly correlated with the improvement in growth rate, suggesting that internal depletion of amino-acids presented the major bottleneck limiting growth in xylulose. We discuss the possible implications of our results for explaining how cells maintain the balance between supply and demand of amino acids during growth in evolutionary 'familiar' vs. 'novel' conditions. Overall design: mRNA profiles of 12 wt S. cerevisiae strains grown on either YPD or YP-xylulose, before and after 300 generations evolution on YP-xylulose
Rapid evolutionary adaptation to growth on an 'unfamiliar' carbon source.
Cell line, Subject
View SamplesMania is a serious neuropsychiatric condition associated with significant morbidity and mortality. Previous studies have suggested that environmental exposures can contribute to mania pathogenesis. We measured dietary exposures in a cohort of individuals with mania and other psychiatric disorders as well as in control individual without a psychiatric disorder. We found that a history of eating nitrated dry cured meat, but not other meat or fish products, was strongly and independently associated with current mania (adjusted odds ratio 3.49, 95% confidence interval (CI) 2.24-5.45, p<8.97x 10-8). Lower odds of association were found between eating nitrated dry cured meat and other psychiatric disorders. We further found that the feeding of meat preparations with added nitrate to rats resulted in alterations in behavior and changes in intestinal microbiota. Rats fed diets with added nitrate also showed alterations of brain pathways dysregulated in mania. These findings may lead to new methods for preventing mania and for developing novel therapeutic interventions
Nitrated meat products are associated with mania in humans and altered behavior and brain gene expression in rats.
Sex, Specimen part
View SamplesTo study the molecular mediators of naturally rewarding effects of palatable food we used a model of palatable snacking (Ulrich-Lai et al., 2007) in which rats are given chronic, brief access to a limited amount of sucrose solution (30%). Single housed, male Long-Evans rats (250g) (n=12 per group) from Harlan Labs (Indianapolis, IN) received normal rat chow (Harlan Teklad) and water ad libitum for the duration of the experiment. After a one-week period of acclimation, rats were randomly assigned to drink treatment groups of either 30% sucrose solution or water. Rats received a 14-day regimen of twice daily (9:30 and 15:30) brief (maximum of 30 minutes) limited (up to 4 mL) access of their assigned drink solution. Drink solutions were delivered via a graduated sipper placed onto the cage top in addition to the existing water bottle and sippers were immediately removed when the animal had consumed 4mL or after the 30-minute access period, whichever occurred first. Drink intake, food intake, and body weight were monitored throughout the experiment to verify that the rats learned to drink sucrose, that they adjusted chow intake for calories consumed from sucrose (~10%), and that there was no effect on body weight gain as is normally seen with this model (Ulrich-Lai et al., 2007). Drink treatment terminated on day 14 and at 8:00 on the morning of day 15, the rats were sacrificed by rapid decapitation. BLA tissue was dissected, RNA extracted, and gene expression changes between water and sucrose groups were accessed by microarray.
Pleasurable behaviors reduce stress via brain reward pathways.
Sex, Specimen part, Treatment
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