Project description:Effect of 17beta-oestradiol (E2) on gene expression in human cardiac tissues and the interaction between the treatment with E2 and the sex.
Project description:The purpose of this study was to assess the impact of sex on gene expression in LV of AS patients at the time of AVR. LV samples of men (n = 9; age: 75 M-1 8 y) and women (n = 10; age: 72 M-1 9 y) undergoing AVR were used for RNA isolation. Genome-wide expression profiling was performed using the Affymetrix platform and the data were analyzed with R and Bioconductor. Diseased samples were compared with LV samples of men (n = 10; age: 56 M-1 4 y) and women (n = 8; age: 56 M-1 5 y) with no apparent cardiovascular disorder.
Project description:Doxorubicin (DOXO), a chemotherapeutic drug, is cardiotoxic. We hypothesized that folic acid is an effective therapeutic agent in a mouse model of DOXO-induced cardiotoxicity. We performed genome-wide expression profiling to identify the underlying mechanisms. Male C57Bl6 2-mo old mice received DOXO (1x20 mg/kg, ip) or saline (sham). FA (10 mg/d) or placebo (plac) was administered 7d before DOXO administration until the end of the experiment (10d).
Project description:The heart of late pregnant (LP) rodents is more prone to ischemia/reperfusion (I/R) injury compared to non-pregnant rodents. We hypothesized that Intralipid (ITLD) protects the heart in LP rodents against I/R injury. We performed genome-wide expression profiling to identify the underlying mechanisms. Female LP rat hearts were subjected to ischemia followed by reperfusion with vehicle or ITLD (one bolus of 5mg/kg).
Project description:Most epithelial ovarian cancers are thought to arise from different cells in the ovarian or fallopian tube epithelium. We hypothesized that these distinct cells-of-origin may play a role in determining ovarian tumor phenotype and also could inform the molecular classification of ovarian cancer. To test this hypothesis, we developed new methods to isolate and culture paired normal human ovarian (OV) and fallopian tube (FT) epithelial cells from multiple donors without cancer and identified a cell-of-origin gene expression signature that distinguished these cell types within the same patient. Application of the OV versus FT cell-of-origin gene signature to gene expression profiles of primary ovarian cancers permitted identification of distinct OV and FT-like subgroups among these cancers. Importantly, the normal FT-like tumor classification correlated with a significantly worse disease-free survival. This work describes a new experimental method for culture of normal human OV and FT epithelial cells from the same patient. These findings provide new evidence that cell-of-origin is an important source of ovarian tumor heterogeneity and the associated differences in tumor phenotype. We analyzed 12 samples from two donor patients and established cultures of both ovarian epithelium and fallopian tube epithelium (hTERT immortalized), each with 3 replicates (different culture passages).
Project description:Mesenchymal Stem Cells have been seeded on calcium based biomaterials. miRNA expression is evaluated at day 0 (unseeded cells), day 5, and day 10, in order to study miRNA differential expressions at different time points and infer if biomaterial induced miRNA expression variation able to differentiate stem cells towards the osteoblasts lineage.
Project description:Colon cancer is one of the most common tumors worldwide. Recent reports showed that patients treated with the antidepressant fluoxetine had reduced colon cancer risk, with effects similar to the chemotherapeutic 5-fluoro-uracil. Here, we examined the effects of fluoxetine and 5-fluoro-uracil on gene expression of HT29 colon cancer cell xenografts. HT29 xenografts in NOD/SCID mice were treated with vehicle (physiological solution), fluoxetine (30mg/kg/day), or 5-Fluoro-uracil (50 mg/kg/day).
Project description:High density cultured CD8+ memory T-cells from peripheral blood mononuclear cells (PBMC) were found to be more sensitive towards antigenic stimulation. We used microarrays to detail the global programme of gene expression underlying differences in the cell density of human PBMC and identified genes that are significantly up- or downregulated dependent on the cell density of PBMC. Paired analysis of CD8+ memory T-cells from fresh and high density precultured PBMC from three healthy donors.
Project description:Research in human immunobiology is mainly based on working with peripheral blood mononuclear cells (PBMC). However, recent investigations have shown that circulating CD4+ T cells are less sensitive to several T-cell activating monoclonal antibodies (mAb) and to recall antigens as compared to tissue-resident cells or cells that were in-vitro cultured at a high cell density of 10^7 cells/mL for 2 days at 37°C and 5% CO2 (RESTORE protocol, Römer et al., Blood 2011, PMID: 21931118). To explain the increase in sensitivity of CD4+ T-cells to mAbs and recall antigens on a molecular level, we performed microarray hybridizations of total RNA from T-cells isolated from PBMC that were cultured at a low or high cell density. To avoid the detection of genes that are up- or down-regulated by the culture process itself, we used low cell density cultured PBMC, instead of freshly prepared PBMC. We used microarrays to detail the global programme of gene expression underlying differences in the cell density of human PBMC and identified genes that are significantly up- or downregulated dependent on the cell density of PBMC. Human PBMC of one healthy blood donor were cultured at a low cell density (10^6 cells/mL) or at a high cell density (10^7 cells/mL) for 2 days at 37°C and 5% CO2 and CD4 or CD8 T-cells of both cultures were isolated by MACSbeads. Expression profiles from total RNA extracts were generated by hybridization to Affymetrix microarrays.