Transcriptional profiling of platinum sensitive and platinum resistant high grade serous ovarian cancer samples
ABSTRACT: This study aims at correlating changes in the transcriptional state in high grade serous epithelial ovarian cancer (HGS-EOC) to the response to therapy, in particular the insurgence of resistance to platinum-based treatment.
Project description:This study aims at correlating changes in the microRNA state in high grade serous epithelial ovarian cancer (HGS-EOC) to the response to therapy, in particular the insurgence of resistance to platinum-based treatment.
Project description:In order to determine the impact on transcription of the novel bromodomain inhibitor OTX015, we treated two triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468) treated with the compound at 24 hours.
Project description:In the last decades platinum-based neo-adjuvant chemotherapy (NACT) has been recognized as a reliable therapeutic strategy in patients with un-resectable advanced epithelial ovarian cancer (EOC). However, the molecular changes induced by NACT at miRNA level, and their prognostic role has not been clarified until now. In order to uncover miRNAs that are altered in EOC tumor which received NACT, we performed whole-miRNA analysis on 82 FIGO Stage IIIC-IV high-grade serous (HGS) tumors, whose samples had been collected at complete primary debulking (PDS) and at interval-debulking surgery (IDS) after fter 4 courses of NACT.
Project description:Colorectal cancer (CRC) is a major cause of cancer mortality and a serious health concern worldwide. Vitamin D deficiency is associated with high CRC incidence and mortality, suggesting a protective effect of vitamin D against this neoplasia. Although the antiproliferative and prodifferentiation action of active vitamin D (1alpha,25-dihydroxyvitamin D3, 1,25(OH)2D3) on colon carcinoma cells is well documented, its potential effects on CRC stroma are unknown. Here, we show that high vitamin D receptor (VDR) expression in tumor stromal fibroblasts is associated with better overall and progression-free survival in a large cohort of CRC patients, irrespective of its expression in carcinoma cells. Consistently, 1,25(OH)2D3 inhibits the activation of patient-derived normal and cancer-associated fibroblasts, and their pro-migratory effect on carcinoma cells. Importantly, we show by global transcriptomic analyses that 1,25(OH)2D3 regulates cancer-associated fibroblast gene expression and imposes a gene signature that is associated with longer overall and disease-free survival of CRC patients. Moreover, expression of two genes from the signature, CD82 and S100A4, correlates with stromal VDR expression and clinical outcome in CRC. This study provides the first evidence that vitamin D has protective effects against CRC through the regulation of stromal fibroblasts. Characterization of 1,25(OH)2D3 action on gene expression in primary cultures of colon normal and tumor fibroblasts established from samples from colorectal cancer patients. RNA from seven paired normal and tumor fibroblast primary cultures treated with 1,25(OH)2D3 or vehicle for 48 h were analyzed.
Project description:A population of non-adherent cells with stem-like characteristics (OVA-BS4 spheres) has been isolated from a primary human epithelial ovarian cancer (EOC) cell line (OVA-BS4) under selective conditions. OVA-BS4 spheres were characterized for their pharmacological properties and their molecular profile by microarray and RT-qPCR.
Project description:In this study, we examined the effects of VOCs exposure in humans on gene expression using microarray analysis. We recruited participants who had short-term exposure, long-term exposure, or no exposure. We then analyzed changes in gene expression in blood samples from these participants. A total of 866 genes were upregulated, while 366 genes were downregulated in the short-term exposure group. Similarly, in the long-term exposure group, a total of 852 and 480 genes were up- or downregulated, respectively. Hierarchical clustering analysis was used to divide the clustered genes into nine clusters to investigate the expression of variations in accordance with the exposure period. Further research is required to determine the time-dependent effects of VOCs on epigenetic regulation of gene expression. Gene expression of mRNA in human blood samples (IRB #AS 14039) divided into three groups: control (unexposed workers; n = 12), short-term exposure (workers exposed to VOCs for less than 10 years; n = 12), and long-term exposure (workers exposed to VOCs for more than 10 years; n = 12) was experimented by microarray analysis after exposure to VOCs
Project description:In order to assess the potential difference on the effect of lurbinectedin on monocytes compared to trabectedin, which has a selective killing effect (Germano et al., 2013), we performed a whole transcriptome assay on monocytes from healthy donors stimulated with LPS and with either trabectedin or lurbinectedin. Doxorubicin, an unrelated drug, was used as an internal control.
Project description:EBV positive PTCL-U is a very rare but aggressive disease entity. To investigate gene expression profile, we performed gene expression analysis using two different types of microarray kits (Agilent chip 4x44K and 8x60K) We compared gene expression between in 3 EBV positive PTCL-Us and in 6 normal reactive lymph nodes.
Project description:In order to study heme-induced global transcriptional changes, we performed a transcriptome-wide analysis of heme influence on the A. aegypti cell line Aag2. As heme-mediated effects on gene expression are thought to be related to oxidative stress, we compared the transcriptional profiles of Aag2 cells challenged with either 50 µM heme or 100 µM of the ROS inducer paraquat, using whole genome microarrays. Three-condition experiment, CTR vs. Heme- or Paraquat incubated cells. Biological replicates: 4 control and 4 experimental replicates.
Project description:To identify microRNAs that regulate therapeutic resistance, we conducted a high-throughput miRNA microarray on a cohort study of primary NSCLC (non-small cell lung cancer) tissues and adjacent normal tissues. We found some microRNAs related to therapeutic resistance and poor prognosis. In this study, the patients who were diagnosed with resected NSCLC (adenocarcinoma or squamous cell carcinoma) were enrolled. All tumors were reviewed by pathologists and were pathologically diagnosed according to the World Health Organisation Classification of Tumors. Twenty-nine patients who received four or more courses of first-line platinum-based chemotherapy after postoperative recurrence were divided into two groups (responder (n=17) and non-responder group (n=12)). As identified by ANOVA analysis and quantitative RT-PCR (qRT-PCR) of 4 groups, some miRNAs exhibited significant expression changes.