Clinical and prognostic relevance of squalene epoxidase in breast cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Patrizio Castagnola
PROVIDER: E-GEOD-71395 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The classical concept of bone marrow-derived mesenchymal stem cells (BM-MSC), intended as a uniform, broad potent population, is progressively being substituted by the idea that the bone marrow harbors heterogeneous populations of non-hematopoietic stem cells. This in vivo heterogeneity is also amplified by the different experimental strategies used to isolate/culture them. Among the exogenous factors described to affect MSC in vitro growth, basic-fibroblast growth factor (bFGF) is one of the most common growth factors used to expand stem cells. Moreover, it has been reported that its signaling is associated with the mainteinance of stemness of a variety of stem cells, included MSC. Using an ectopic model of bone regeneration, we have previously described that the implantation of cells with different commitment levels, differentially influences the capacity to recruit host cells, activating endogenous regenerative mechanisms. Due to its properties, we here demonstrate that the addition of bFGF to primary BM cultures, leads to the selection of specific subpopulations able to induce a different host regenerative response, when in vivo implanted in association with suitable ceramic scaffolds. Moreover, taking advantage of a multiparametric and comparative genomic and proteomic approach, it has been evaluated how different culture conditions combine to bring about appreciable changes in the secretome of the cells, that consequently influence their in vivo regenerative behaviour. The full comprehension of the regulatory mechanisms that rule the host response depending on the type and differentiative stage of the transplanted cells could help us to develop novel clinical strategies where host cells could directly contribute to regenerate the appropriate tissue. Comparison of bFGF effects on bone marrow mesenchymal stem cells.
2011-09-30 | E-GEOD-30541 | biostudies-arrayexpress
Project description:Mutations of the proto-oncogene KRas, together with the inactivation of the onco-suppressor genes APC and TP53, are considered to have an important role both in the carcinogenesis and in the colorectal tumor progression. The oncogene K-ras has activating mutations, especially in codon 12, in about 40% to 50% of colorectal carcinomas (Andreyev et al., 1998). The mechanism by which oncogenic K-ras alone contribuites to tumor progression in colon cancer is largely unknown. To this end, we have developed a model system where the colorectal adenocarcinoma cell line Colo741 has been stably trasfected with the Kras-G12V or Kras-G12D mutated oncogenes. Our results demonstrate how expression profiling data can be used to interpret changes in cellular characteristics induced by transfection and hence provide some clues as to the mechanisms by which different activated K-Ras impair processes mediated by endogenous wild-type KRas proteins. We made for the production of cell clones that could be utilized as useful in vitro models. The adenocarcinoma cell line Colo741 has been chosen to produce stable transfectants for two mutant forms of KRas2 (Gly12Val and Gly12Asp) and the wild-type coding sequence (as experiment control). After the transfection, the cells have been selected (with G418), cloned (by limited dilutions) and screened (by RT-PCR). The total RNAs, Dnase-treated, from five cell clones per condition, have been pooled. The samples, constituted by biotin-labeled cRNA, derived from a pool of five cell clones obtained from transfection of the adenocarcinoma cell line Colo741 with either pcDNA3.1-KRas2(Wt) or pcDNA3.1-KRas2(Gly12Val) or pcDNA3.1KRas2(Gly12Asp). They were hybridized to a Human Gene 1.0 ST array (Affymetrix). Two technical replicates have been performed for each condition.
2008-12-17 | E-GEOD-12398 | biostudies-arrayexpress
Project description:microRNA regulates cellular responses to ionizing radiation (IR) through the translational control of target genes. We analyzed time-series changes in microRNA expressions upon γ-irradiation in H1299 lung cancer cell lines using microarray. Significantly changed microRNAs were selected based on ANOVA analysis, target genes of which were enriched to MAPK signaling pathway. Concurrent analysis of mRNA and microRNA uncovered that the expression of miR-26b and its target ATF2 mRNA were inversely correlated in γ-irradiated H1299 cells. The overexpression of miR-26b induced the suppression of ATF2 in γ-irradiated cells. When we inhibit the MAPK signaling pathway using SP600125, JNK inhibitor, the expression of miR-26b was induced even in γ-irradiated H1299 cells. From these results, we concluded that the expression of miR-26b was coordinated regulated by MAPK signaling pathway upon ionizing radiation, and MAPK signaling pathway was regulated by miR-26b in turn. We analyzed the time-series miRNA profiles of radioresistant H1299 cells in response to 2 Gy of ionizing radiation (IR) by performing quadratic regression (QR) analysis to identify genes associated with radioresistance
2011-09-13 | E-GEOD-30075 | biostudies-arrayexpress
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.
2018-01-15 | E-MTAB-5366 | biostudies-arrayexpress
Project description:Background: Tyrosine kinase inhibitors (TKIs) are widely used for treating solid and hematologic malignancies. However, their efficacy is frequently short lived, warranting the search for safe potentiation strategies. Short courses of fasting were shown to sensitize cancer cells to chemo- and radiotherapy while increasing the resistance of healthy tissues to the same agents. The purpose of this study was to assess the potential of fasting to increase the efficacy of TKIs. Methods: starvation-mimicking culture conditions were studied for their ability to potentiate the effects of Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), Anaplastic Lymphoma Kinase (ALK) and multitarget TKIs in terms of cancer cell growth, signaling cascades inhibition, and changes in gene expression profile in TKI-sensitive cancer cells. In vivo, the activity of crizotinib or regorafenib, weekly cycles of fasting, or their combination was compared in tumor xenografts models. Results: In vitro, starvation-mimicking culture conditions increased the ability of TKIs to block cancer cell growth and to inhibit the mitogen-activated protein kinase (MAPK) signaling pathway. At the gene expression profile level, starvation and crizotinib led to similar changes, but their combination strengthened Rb-, MYC-, and E2F-dependent transcription inhibition. In vivo, both TKIs and cycles of fasting slowed tumor growth, but, when combined, they were significantly more effective than either type of treatment alone. Conclusions: Cycles of fasting or of specifically designed fasting-mimicking diets should be evaluated in clinical studies as a means to potentiate the activity of TKIs in clinical use. RNA was collected from H3122 cells in 4 different conditions: serum, starvation, treated with Crizotinib, starvation and treated with Crizotinib. Each condition was run in quadruplicate
2016-07-03 | E-GEOD-62663 | biostudies-arrayexpress
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goal of this study is to analyse the whole transcriptome of MSCs stimulated with TGFα in order to comprehensively assess the genes regulated by EGFR signalling Methods: Libraries of cDNA were obtained from poly(A)-RNA fractions from not-stimulated or TGFα-stimulated MSCs and sequenced with a SOLiD 5500xl platform. Whole-transcriptome reads were aligned to the version 19 of the human genome (hg19) with the SOLiD LifeScope Genomic Analysis Software version 2.5 (Life Technologies) using the parameters recommended in the user’s manual. The number of observed counts (number of reads/gene) was normalized for the length of the transcript and the number of mapped reads (RPKM) (Reads Per Kilobase per Million of mapped reads). DESeq tool in R package was used to obtain a statistical evaluation of differential gene expression. Results: 1,640 genes resulted highly differentially regulated: 967 genes up-regulated with Fold Induction (FI)≥1.50, and 673 genes down-regulated with FI≤0.50. When highly regulated genes were categorized into enriched categories according to GO molecular function classification and KEGG pathways analysis, a large number of genes coding for potentially secreted proteins or for surface receptors resulted enriched following TGFα treatment. In particular, significant up-regulation of VEGFA, IL6, EREG, HB-EGF, LIF, NGF, NRG1, CCL19, CCL2, CCL25 and CXCL3 was observed. Conclusions: Taken together these findings suggest that EGFR activation in MSCs leads to a significant change in the expression of a wide array of genes coding for secreted proteins that can significantly enhance tumor progression by acting on several mechanisms within the tumor microenvironment mRNA profiles of MSCs starved overnight in serum free medium and treated for 1 hour with recombinant at a concentration of 10 ng/ml by deep sequencing, in quadruplicate, using SOLiD 5500xl.
2015-06-26 | E-GEOD-60560 | biostudies-arrayexpress
Project description:miR-142-3p is highly expressed in peripheral blood mononuclear cells (PBMCs) and has been described as a hematopoietic-restricted lineage, suggesting immune functions (Chen, Li et al. 2004; Landgraf, Rusu et al. 2007; Merkerova, Belickova et al. 2008). In order to determine the roles of miR-142-3p in B lymphocytes, we over-expressed this miRNA in the Raji B-cell line using a synthetic mimic of miR-142-3p and analyzed gene expression 24 hours after the transfection. Four replicates each of miR-142-3p-mimic transfection and apparied control mimic.
2011-05-30 | E-GEOD-28456 | biostudies-arrayexpress
Project description:Tremella fuciformis is a popular edible fungus with fruiting bodies that can be produced in large quantities at low costs, while it is easy to transform and cultivate as yeast. This makes it an attractive potential bioreactor. Enhanced heterologous gene expression through codon optimization would be useful, but until now codon usage preferences in T. fuciformis remain unknown. The only available genome of a species in the genus Tremella was that of Tremella mesenterica. To precisely determine the preferred codon usage of T. fuciformis we sequenced the genome of strain Tr26 resulting in a 24.5 Mb draft genome with 10,040 predicted genes. 3288 of the derived predicted proteins matched the UniProtKB/Swiss-Prot databases with 40% or more similarity. Corresponding gene models of this subset were subsequently optimized trough repetitive comparison of alternative start codons and selection of best length matching gene models. For experimental confirmation of gene models, 96 random clones from an existing T. fuciformis cDNA library were sequenced, generating 80 complete CDSs. Calculated optimal codons (RSCU and RFCU values) for the 3288 predicted and the 80 cloned CDSs were highly similar, indicating sufficient accuracy of predicted gene models for codon usage analysis. T. fuciformis showed a strong preference for C and then G (C+G; 66.4 %) at the third base pair position of used codons, while average GC content of predicted genes was slightly higher (58.5 %) than he total genome sequence average (55.9%). Most frequently used codons (optimal codons) all ended in C or G except for one (Ter; AGU), and an increased frequency of C ending codons was observed in genes with higher expression levels. Surprisingly, the preferred codon usage in T. fuciformis strongly differed from T. mesenterica (same genus) and C. neoformans (same family). Instead, optimal codon usage was similar to more distant related species such as Ustilago maydis and Neurospora crassa. Despite much higher overall sequence homology between T. fuciformis and T. mesenterica only 7 out of 21 optimal codons were equal, whereas T. fuciformis shared up to 20 out 21 optimal codons with other species. Clearly, codon usage in Tremella can differ largely and should be estimated for individual species. The precise identification of optimal and high expression related codons is therefore an important step in the development of T. fuciformis as a bioreactor system. Using the Total RNA was extracted from yeast-like cells of T. fuciformis Tr21 in their exponential growth stage, and double-stranded cDNA was synthesized for tag library construction and digital gene expression tag (DGE) sequencing at BGI Tech Solutions Co., Ltd (Shenzhen, China). Image analysis, base calling, extraction of tags, and tag counting were conducted using the Illumina pipeline. Clean tags were mapped to predicted gene models of the draft genome with a mismatch tolerance of 1bp. The number of tags for each CDS was calculated and then normalized to TPM (number of transcripts per million clean tags) digital gene expression (DGE)
2015-04-20 | E-GEOD-68023 | biostudies-arrayexpress
Project description:To get further insights into the processes leading to attenuation of early stage atherosclerosis in the bortezomib treated LDLR-KO mice, microarray profiling of gene expression was performed on RNA taken from whole aortae of bortezomib treated LDLR-KO and sham- treated LDLR-KO mice fed a Western diet for 6 weeks and compared the changes in gene expression in both groups to non-atherosclerotic CD animals. Male 10-week-old LDLR-KO mice (B6.129S7-Ldlrtm1Her/J; JAX Mice, Boston) were fed a Western-type diet for 6 weeks ad libitum and received intraperitoneal injections of bortezomib (50 µg/kg body weight; WD+Bor) or saline (WD) twice weekly (n = 4). Mice that were fed normal diet served as chow diet control (CD; n = 4). Gene expression in aortic tissue was measured. Two independent experiments were performed.
2011-07-13 | E-GEOD-30638 | biostudies-arrayexpress
Project description:Hypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology, as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques. Our main goal is to define a robust hypoxia gene signature in neuroblastoma cell lines. A set of 11 neuroblastoma cell lines were cultured under normoxic and hypoxic conditions for 18 hours, and their gene expression profiles were measured with Affymetrix GeneChip HG-U133 Plus 2.0. We used the l1-l2 regularization framework in order to select the significant probesets defining hypoxic versus normoxic cell lines. Experiment Overall Design: The expression profiles of 11 neuroblastoma cell lines under normoxia vs hypoxia were studied.
2009-10-10 | E-GEOD-17714 | biostudies-arrayexpress