IGR_EPENDYMOMA_STUDY_MP
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Philippe DESSEN
PROVIDER: E-TABM-873 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Background: Although histology is the corner stone for decision analysis in bladder cancer, it still needs refinement and new tools to better identify tumours with the highest risk of progression or recurrence. Objective: We designed a prospective study to evaluate whether microarray analysis could find a molecular signature for pathologic staging and/or grading. Design, setting and participants: Prospective multicentric study conducted from September 2007 to May 2008 (108 bladder tumours (45 pTa, 35 pT1 and 28> pT1)). Microarray analysis was performed with Agilent Technologies Human Whole Genome 4 x 44K oligonucleotide microarrays and used a method of dual color type versus a reference consists of a pool of tumours. From the lists of genes provided by the BrB Class Comparison analyses, we validated the microarray results of 38 selected differentially expressed genes by RT-QPCR in another bladder tumour cohort (n = 95). Results: The cluster M-^Ssuperficial vs invasive stageM-^T properly classified 92.9% of invasive stages and 66.3% of superficial stages. Among the superficial tumours, the cluster analysis showed that pT1b tumours were closer to invasive stages than pT1a tumours. We also found molecular differences between low and high-grade superficial tumours. However these differences were less caricatural than the one observed for staging.Conclusions: We confirm that the histopathological classification into subgroups pTa, pT1a and pT1b may have a translation in a M-^Smolecular signatureM-^T with a continuous progression of deregulation (overexpression or repression of these genes) from superficial (pTa) to more invasive (pT1a then b stage).
2013-08-13 | E-MTAB-993 | biostudies-arrayexpress
Project description:Characterize the genes deregulated in CD34 positive cells from peripheral blood of FPD/AML patients harbouring two different RUNX1 mutations. RUNX1 (also called AML1), a DNA-binding subunit of the CBF transcription factor family, is a master regulatory gene in hematopoiesis and acts as a tumour suppressor. Heterozygous germ line alterations in RUNX1 lead to a familial platelet disorder with a propensity to develop acute myeloid leukemia (FPD/AML). Although RUNX1 abnormalities per se are not sufficient to induce full-blown leukemia in FPD, this pathology represents a valuable model to understand how RUNX1 germ line mutations predispose to acquisition of additional genetic changes leading to leukemia transformation. To investigate how RUNX1 may predispose to leukemia, we performed a comparative study between two pedigrees harbouring different RUNX1 mutations, one associated with only thrombocytopenia (R139stop) and the other leading to thrombocytopenia and leukemic predisposition (R174Q).
2010-09-11 | E-TABM-792 | biostudies-arrayexpress
Project description:The IGR-Heu tumor cell line was established from patient Heu suffering from large cell carcinoma of the lung. Heu171, Heu127 and Heu161 T cell clones were isolated from autologous tumor infiltrating lymphocytes. H32 T cell line and H32-22 clone were isolated from autologous PBL after stimulation with IGR-Heu and sorting with peptide-MHC tetramers. T cells were grown in the presence of irradiated autologous tumor and lymphoblastoid cell lines in complete media supplemented with rIL-2 and conditioned medium from phytohemagglutinin-activated lymphocytes for 3 weeks. Then, for microarray assays, RNA was extracted from the different cells.
2007-03-02 | E-TABM-208 | biostudies-arrayexpress
Project description:Hypoxia-mediated inhibition of specific tumour cell lysis
2009-03-12 | E-TABM-611 | biostudies-arrayexpress
Project description:Docetaxel is used as a standard treatment in patients with metastatic castration-resistant prostate cancer. However, a large subset of patients develops resistance by mechanisms that remain largely unknown. It is thus important to define the relevant pathways implicated in docetaxel-resistance and validate predictive biomarkers that will allow approaches of personalized treatment. In this aim, we established resistant IGR-CaP1 prostate cancer cell lines to different doses of docetaxel (IGR-CaP1-R cell lines) and investigated gene expression profiles by microarray analyses. We generated a signature of 112 genes potentially implicated in docetaxel-resistance whose expression is highly modified (Fold change M-bM-^IM-% 5). Among these genes, significant modification of expression was observed among cell cycle components in the resistant cells. Hence, we focused on the role of the cell cycle regulator LZTS1 located on chromosome 8p which was under-expressed in all our docetaxel-resistant models. LZTS1 extinction was confirmed at the RNA and protein levels. DNA methylation analysis revealed a stretch of 20 highly methylated CpGs in the region encompassing the exon 1 of LZTS1 promoter in the docetaxel-resistant cells suggesting the existence of an epigenetic regulation of LZTS1 expression in the resistant cells. By using siRNA strategy, we found evidence that LZTS1 plays an important role in the acquisition of the resistant phenotype. In addition, immunohistochemical staining showed that LZTS1 protein was absent or down-regulated in 33% of diagnostic biopsies obtained in patients with metastatic castration-resistant prostate cancer. This heterogeneous labeling suggests that LZTS1 might constitute a predictive biomarker of response to docetaxel chemotherapy. Furthermore, as Cdc25C is a LZTS1 partner in the mitosis regulation, we observed that targeting of Cdc25C with the pharmacological Cdc25C inhibitor NSC 663284 specifically killed the docetaxel-resistant cells. These results strongly suggest that Cdc25C plays a role in docetaxel resistance and that Cdc25C might be a therapeutic target to overcome docetaxel resistance. Altogether our findings identify an important role of LZTS1 in developing docetaxel resistance in prostate cancer through its role in regulating phosphatase Cdc25C. The set of gene expression with 4x44K Agilent ( design 014850) correspond to 6 doses of docetaxel 2?5 to 200 ug/ml) in dual color and dye-swap versus the IGR-Cap1 cell line without docetaxel.
2013-06-30 | E-MTAB-1221 | biostudies-arrayexpress
Project description:Context : Non Functioning Pituitary Adenomas (NFPAs), although typically benign, may be locally invasive. Few datas are currently available related to the molecular process of invasion in sporadic pituitary adenomas. Markers of invasiveness, important for helping the clinician in the therapeutic strategy particularly in the decision for adjuvant radiotherapy, are currently lacking. Objective: Evaluate if invasive NFPAs display a specific expression profile compared with non invasive tumors. Methods: To address this issue, we selected 40 NFPAs (38 of the gonadotroph type) and classified them as invasive (n=22) or non invasive (n=18) on the basis of MRI and surgical findings. Then we performed pangenomic analysis based on Agilent Human Whole genome Gene Expression oligonucleotide microarray (44k) Expression in order to identify genes differentially expressed between invasive and non invasive NFPA. Experiements are made in dual color with tumor samples labelled in cyanine 5 and a pool of all tumors labelled in cyanine 3.The expressions of some genes identified by microarray screening were confirmed by real-time quantitative RT-PCR. The selection of genes was made on the basis of Ingenuity networks and degree of upregulation between invasive and non invasive tumors. Moreover, some genes of interest already described in the literature were added to the analysis. Results: Prediction class analysis showed that 346 genes discriminated between invasive and non invasive NFPAs (p<0.001); 233 were up- and 113 were down-regulated between the two groups. We then tested On the basis of Ingenuity networks and degree of upregulation between invasive and non invasive tumors, a set of eight genes, including MYO5A, IGFBP5, FLT3, NFE2L1, PTTG, MMP9, NCAM and NR1H3, was tested in quantitative PCR analysis and. Results confirmed those obtained in microarrays results.analysis. At the protein level, Myosin 5A (MYO5A) demonstrated stronger immunostaining in invasive NFPAs compared to non invasive NFPAs. Conclusions: We propose a molecular signature of eight genes of grossly invasive NFPAs as compared with non invasive tumors: The product of one of these genes, MYO5A, may be a useful marker of invasive process in tumoral specimens. The role of these genes in the invasiveness process and as prognostic markers of pituitary adenomas needs to be confirmedinvestigated. Method: Microarray analyses the transcriptome of 22 invasive Non Functional Pituitary Adenomas (NFPAs) and 18 non invasive NFPAs in dual color (each sample labelled in cyanine 5 and a pool of all tumors labelled in cyanine 3).
2010-03-18 | E-TABM-899 | biostudies-arrayexpress
Project description:'Prostate cancer is the second cancer diagnosed among men worldwide. Beside approval of new therapies in the last five years, chemotherapeutic agents, docetaxel and cabazitaxel taxanes remain key treatments for metastatic castration resistant prostate cancers. However, primary and acquired resistance to taxanes still emerged in about half of patients. There is therefore an urgent need to discover and understand the taxane resistance mechanisms in order to identify new therapeutic targets. Indeed, targeted therapies that exploit the signaling pathways involved in prostate cancer are required to overcome chemoresistance and improve treatment outcomes. Molecular chaperones play a key role in the regulation of cellular homeostasis and the development of treatment resistance, and are promising therapeutic targets. Using high throughput siRNA functional screening based on a gene expression signature, we identified FKBP7, involved in acquired resistance to docetaxel and cabazitaxel. FKBP7 is a molecular chaperone that has not been studied in human so far. FKBP7 is overexpressed in prostate tumors and its expression is correlated with recurrence in patients who received docetaxel as neoadjuvant therapy. Moreover, FKBP7 is upregulated in taxane resistant prostate cancer cell lines and its expression sustains their growth in vitro and in a mice model of Docetaxel resistance. Using a high throughput proteomic approach, we identified the signaling pathway regulated by FKBP7 which is responsible for the survival of chemoresistant cells. Finally, we proposed a promising therapeutic strategy to overcome both docetaxel and cabazitaxel chemoresistance by targeting the downstream effector of FKBP7. Gene expression was profiled using a 4×44K Human Whole Genome (G4112F, id : 014850) expression array (Agilent Technologies, Santa Clara, Cal.) with a dual color dye-swap competitive hybridization procedure, according to the manufacturer''s instructions. Total RNA from untreated parental IGR-CaP1 cells was used as the RNA reference (NN1). Total RNA from IGR-CaP1 cells resistant to 5nM (NN2), 11.6nM (NN3), 25nM (NN4), 50nM (NN5), 100nM (NN6), and 200nM (NN7) of Docetaxel respectively, were used as samples. Two independent replicates of each samples (a and b) were used. Image analyses (quantification, normalization) were performed with Feature Extraction software (Agilent Technologies) and gene expression analysis was performed using Bioconductor.'
2018-11-07 | E-MTAB-4869 | biostudies-arrayexpress
Project description:The OTT1-MAL fusion oncogene is specifically associated with human infant acute megakaryoblastic leukemia. In a murine model of OTT-MAL expression, leukemic cells expressing OTT-MAL present an aberrant activation of the Notch pathway target genes. IKZF1 was proposed to interact with the Notch signaling pathway during T-cell development and leukemogenesis. IKZF1-deficient animals present thrombocytosis with increased number of megkaryocytes indicating that it plays a role during megakaryocyte development. To assess the interaction betweeen the Notch signaling pathway and Ikaros in the context of acute megakaryoblastic leukemia, we expressed full-length IKZF1 in a cell line expressing the fusion OTT-MAL (6133 cells). To identify the target gene of IKZF1 we performed a global expression analysis as follow: i) 6133 cells were infected with the following retroviruses :1-empty retrovirus (MIE) 2-retrovirus allowing the expression of the full-length IKZF1 (IK1) and 3- a retrovirus allowing the expression of an alternatively spliced form of IKZF1 (IK7). Ii) Infected cells were sorted by flow cytometry 24 hours after infection and RNA was extracted with the Qiagen Rneasy kit with DNase treatment. After quantification biological replicates of RNA were hybridized on Agilent arrays with dye-swap as indicated below.
2013-08-08 | E-MTAB-897 | biostudies-arrayexpress
Project description:The molecular bases of cellular changes that occur during ontogeny of human megakaryopoiesis remained unknown. We performed global gene expression profiling of pure populations of megakaryocytes (MK) derived from ES cells (MKES), fetal liver (MKFL), cord blood (MKCB) and adult blood (MKAD). A close pair-wise relationship between MKES and MKFL and between MKCB and MKAD was detected, respectively. A modest number of genes (695) was found differentially regulated along development. Major changes occurred in genes encoding cytoskeleton, platelet membrane and a-granule proteins, suggesting a functional MK maturation during development. MK ontogeny-associated changes in the expression of cell cycle regulators (e.g. AURKA, AURKB, PLK1) may account for the progressive increase in cell ploidy observed all along ontogeny. Several genes, including lin28B, were specific for embryonic and fetal MK whereas others, like CXCR4, were specific of the neonate and adult stage. In accordance with the absence of CXCR4 expression in embryonic MK, their migration was independent of SDF1, which functionally validates the changes in gene expression. Finally, the pattern of transcription factor network and signaling pathways (GATA1, SRF, MYC and Notch pathway) was consistent with the hypothesis that de novo acute megakaryoblastic leukemia, which predominantly affects children, develop from early MK. This transcriptomic analysis is dedicated to identify genes that are diffentially expressed during human megakaryocyte ontogeny. To that purpose, several samples of MK were differentiated from human embryonic stem cell lines (MKES1 to MKES4), from CD34 positives cells of fetal liver (MKFL1 to MKFL3), of cord blood (MKCB1 to MKCB3) or from adult blood (MKAD1 to MKAD3). These samples were hybridized in dual color and dye-swap on 8x60K Agilent whole genome human array (design 028004).
2013-06-24 | E-MTAB-1452 | biostudies-arrayexpress
Project description:In most mammalian species, a critical step of placental development is the fusion of trophoblast cell into a multinucleated syncytiotrophoblast layer, which separates the fetal and maternal blood circulations. Advancement in understanding this process came from the identification of two pairs of envelope genes of retroviral origin, independently acquired by the human (syncytin-1 and M-^V2) and mouse (syncytin-A and M-^VB) genomes, specifically expressed in the placenta and with in vitro cell-cell fusion activity. We previously showed that syncytin-A is involved in the formation of one of the two syncytiotrophoblast layer of the mouse placenta -ST-I , facing the maternal lacuna- with syncytin-A null embryos dying at mid-gestation, and their placenta disclosing impaired formation of the ST-I layer. Here by generating syncytin-B KO mice, we demonstrated that syncytin-B null placenta have defects in formation of the syncytiotrophoblast layer-II facing the fetal blood vessels, with refined electron microscopy analyses showing evidence of unfused apposed cells. Lack of trophoblast fusion is associated with signs of trophoblast degeneration and with formation of huge maternal blood lacuna, ultimately disrupting the architecture of the labyrinth layer. These alterations did not result in complete abortion of syncytin-B null embryos, at variance with the syncytin-A KO phenotype, but in a reduced proportion of homozygous syncytin-B knockout individuals at birth, with evidence of late-onset embryonic growth retardation. Double knockout mice experiments demonstrate a premature death of syncytin-A null embryos if syncytin-B is deleted, thus strongly suggesting cooperative involvement of both syncytiotrophoblast layer-I and layer-II for the structural and functional integrity of the maternofetal interface and exchanges. Finally, a microarray analysis of wild-type and syncytin-B null placenta transcripts disclosed alterations in gene expression level for only a very limited number of genes, with the largest change (a 7-fold induction in the syncytin-B null placenta) observed for the connexin-30 gene. Immunohistochemistry further localized the connexin-30 protein in the labyrinth zone of mutant placenta, at the level of the fetomaternal interface. It is proposed that this might correspond to a compensatory process whereby disruption of syncytialization in syncytin-B knockout placenta is counteracted by an enhanced, gap junction mediated, cell-cell communication. These data demonstrate that syncytin-B is required for ST-II syncytial differentiation and the functional integrity of the labyrinth. Altogether, these findings definitively demonstrate that the two endogenous retroviral syncytin-A and -B Env genes contribute independently to the formation of the two syncytiotrophoblast layers during placenta formation, and provide additional insights into the subtle mechanisms of syncytiotrophoblast differentiation in the mouse. Experimental design: Placenta RNA of embryos homozygous for the syncytin-B deletion (SynB-/-) were compared to placental RNA of wild-type embryos (SynB+/+) of the same litter. Two stages of gestation, day 12 and d14, were analyzed. At day 12, 3 litters were obtained; for two of them, the RNAs were analyzed individually, and for the third one, placenta RNAs of the wild-type genotype were pooled. At day 14, one litter was obtained; RNA samples with the same genotype were pooled
2011-10-19 | E-TABM-1188 | biostudies-arrayexpress