Transcriptional profiling of human breast tumor samples before and after treatment with chemotherapy with and without bevacizumab.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Olav Engebråten
PROVIDER: E-MTAB-4439 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Female breast cancer patients who underwent surgery for breast cancer as part of the Danish Center for Translational Breast Cancer Research program were included from 2003 to 2012. Patient inclusion criteria were: (1) a unifocal tumor with an estimated size of more than 20 mm in diameter, (2) none of the patients had a history of breast surgery and (3) none received preoperative treatment. Patients were defined as high risk according to the Danish Breast Cooperative Group (www.dbcg.dk) and were followed after surgery.
2018-11-16 | E-MTAB-7201 | biostudies-arrayexpress
Project description:hTERT/cdk4 immortalized myogenic human cell lines represent an important tool for skeletal muscle research, being used as therapeutically-pertinent models of various neuromuscular disorders and in numerous fundamental studies of muscle cell function. However, the cell cycle is linked to other cellular processes such as integrin regulation, the PI3K/Akt pathway, and microtubule stability, raising the question as to whether transgenic modification of the cell cycle results in secondary effects that could undermine the validity of these cell models. Here we subjected healthy and disease lines to intensive transcriptomic analysis, comparing immortalized lines with their parent primary populations in both differentiated and undifferentiated states, and testing their myogenic character by comparison with non-myogenic (CD56-negative) cells. We found that immortalization has no measurable effect on the myogenic cascade or on any other cellular processes, and that it was protective against the systems level effects of senescence that are observed at higher division counts of primary cells. This dataset includes gene expression profiles for 94 samples comprising primary myoblasts and their corresponding immortalized clones in both differentiated and undifferentiated states (average of 4 cell culture replicates each) from 5 human subjects (2 healthy and 3 Duchenne muscular dystropy - DMD), together with primary populations of non-myogenic (CD56-ve) cells from the muscles of 8 other human subjects. Total RNA was extracted from, myoblasts, myotubes (after 9 days of differentiation), or CD56-ve cells by dissolving cell pellets in TRIzol then using PureLink RNA Mini Kit.
2016-03-16 | E-GEOD-79263 | biostudies-arrayexpress
Project description:Many enigmas surround different aspects of freshwater eel biology and life cycle. In the same way different hypothesis about why eels are disappearing from European continental waters have been proposed. One such proposal defends that poor fat accumulation of eels, due to pollution in continental waters, might be stopping eels from reproductive migration to the Sargasso Sea. Thus, habitat deterioration could be blamed for the decline in the catchment potential of the European rivers. In this context, and with the aim to study the mode of action of environmentally relevant chemicals in eels, the multi tissue transcriptome was sequenced (454 Titanium Roche) in order to design a high density custom oligonucleotide microarray (eArray, Agilent). To validate this tool a laboratory experiment was carried to analyze the gene trasncrition profiles related to chemical compounds released from pulp and paper mills; 100 μg/L mercury and 150 μg/L β-sitosterol (only Hg data is presented here). 20 yellow European eel (Anguilla anguilla) elvers (11.7±5.35 g) obtained from a local farm (Acuivas SL, Usurbil, Gipuzkoa) were exposed for 3, 6 and 9 days. Pyrosequencing allowed the design and construction of a 60K microarray platform containing 3923 gene signatures identified through BlastN analysis and 7212 sequences annotated through BlastX coupled to Blast2Go analysis. Additional 226 sequences were incorporated from NCBI databases and 3551 from the information available in EeelBase in 2011. Two probes were generated per sequence and they were spotted twice in the array. Hepatic gene expression profiling of the exposed eels indicated that Hg significantly down-regulated (LIMMA, adj. p<0.005) only gene signatures related to selenoprotein W-1 (SeW), something typically described in mammals exposed to methyl-mercury. Increasing the adj. p value to <0.05, 116 genes were significantly regulated (38 down-regulated and 79 up-regulated). Among them, we found additional selenoproteins such as ROS metabolism related genes; glutathione peroxidases (gpx1 & gpx4b) and thioredoxine which were up-regulated. In addition, complement system genes (C3 & C4b) were also up-regulated. Studying enriched Go pathways (p<0.005) and in relation with lipid homeostasis we observed that the following pathways were enriched after exposure to Hg: fatty acids degradation and metabolism of arachidonic acid, linoleic acid, ether lipids, alpha linolenic acid, and glycerophospholipids. In addition, among the top 10 significantly enriched KEGG pathways, p53 signalling, apoptosis, and MAPK signalling were present, suggesting possible effects on cell cycle regulation. In summary, transcriptome pyrosequencing and subsequently designed microarray provided the molecular tools to successfully study the gene transcription profiles of toxic chemical compounds such as Hg in European eel tissues. In addition to study the molecular modes of action of specific chemical compounds, the developed gene expression microarray will be useful in active monitoring of the quality of freshwater environments using caged sentinel eels. This study was funded by Basque Government (SAIOTEK S-PE09UN32; Consolidated Research Groups IT810-13) and UPV/EHU (UFI 11/37). Technical and human support provided by SGIker (UPV/EHU) is acknowledged. An exposure laboratory experiment was performed in the âUr Biologia eta Experimentazio Zerbitzuaâ (UBEZ) of the University of the Basque Country (UPV/EHU) A total of 84 eels, 20.23 ± 2.84 cm in length, were acclimatized to laboratory conditions for 2 weeks in a 10 L water glass tanks under controlled conditions: 12 h light/dark cycle at 18oC, conductivity 600 μS. During this period animals were fed with commercial flakes. Ammonium, nitrites and nitrates kits (Sera GmbH) were used to systematically asses the levels of nitrogenous compounds which were maintained at 0-0.5mg/l; 0-0.5 mg/l, and 5-10 mg/l, respectively. When highest concentrations within those ranges were achieved seawater was partially replaced. A day before exposure experiment, animals were placed in 4 aquaria with 8 L of water at 600 μS. In each aquarium 21 eels were randomly distributed and exposed to: metal-mercury (Hg) (Fluka-Sigma-Aldrich) at a concentration of 100μg/L; and to a phitosterol, β-sitosterol (Sigma) at a concentration of 150 μg/ L. The last compound needed ethanol (0.01%) as vehicle. In addition to an ethanol control group, a water control (600μS) without contaminant was also prepared. Water used during the experiment was filtered at 0.5mm and treated with UV light. Toxic metabolites were measured everyday during experiment using ammonium, nitrites and nitrates test (Sera GmbH), and water was partially replaced every day. Eels were fed everyday with 10mg of commercial food per eel. After 3, 6 and 9 days exposure (T1, T2 and T3 respectively) 7 eels were anaesthetized with 3-aminobenzoate methylsulfonate salt (Sigma-Aldrich). Size and weight were measured for Fulton´s conditioning index assessments, and liver was dissected and frozen with RNA later® in liquid nitrogen for molecular studies.
2016-07-31 | E-GEOD-53344 | biostudies-arrayexpress
Project description:Enhanced understanding of differential gene expression and biological pathways associated with distinct phases of intramembranous bone regeneration following femoral marrow ablation surgery will improve future advancements regarding osseointegration of joint replacement implants, biomaterials design, and bone tissue engineering. A rat femoral marrow ablation model was performed and genome-wide microarray data were obtained from samples at 1, 3, 5, 7, 10, 14, 28, and 56 days post-ablation, with intact bones serving as controls at Day 0. Bayesian model-based clustering produced eight distinct groups amongst 9,062 significant gene probe sets based on similar temporal expression profiles, which were further categorized into three major temporal classes of increased, variable, and decreased expression. Differential biological processes and pathways associated with each major temporal group were identified, and significantly expressed genes involved were visually represented by heat maps. It was determined that the increased expression group exclusively contains genes involved in pathways for matrix metalloproteinases (MMPs), Wnt signaling, TGF-β signaling, and inflammatory pathway. Only the variable expression group contains genes associated with glycolysis and gluconeogenesis, Notch Signaling Pathway, natural killer cell mediated cytotoxicity, and B cell receptor signaling pathway, among others. The decreased group exclusively consists of genes involved in heme biosynthesis, p53 signaling pathway, and hematopoietic cell lineage. Significant biological pathways and transcription factors expressed at each time point post-ablation were also identified. These data present the first temporal gene expression profiling analysis of the rat genome during intramembranous bone regeneration induced by femoral marrow ablation. In an Institutional Animal Care and Use Committee (IACUC) approved study, 27 adult male rats (Sprague Dawley, 400-425 g) were divided into nine groups: intact control (0 day), and 1, 3, 5, 7, 10, 14, 28, and 56 days post marrow ablation. Twenty-four animals received unilateral femoral ablation. At each time point, animals were killed in a carbon dioxide chamber, and whole femurs were harvested and denuded of soft tissue. For three samples per time point, both the distal and proximal ends of the femurs were cut off in order to exclude the epiphyses and growth plate regions. Diaphyseal marrow tissue and cells from the mid-shaft were flushed out using Trizol®. Extracted RNA was homoginized and was prepared for hybridization. For each of the three samples per time point, gene expression was analyzed with GeneChip® Rat Genome 230 2.0 Arrays (Affymetrix, Santa Clara, CA).
2010-10-12 | E-GEOD-22321 | biostudies-arrayexpress
Project description:Lung cancer cell line, A549 cells, was transfected with siPML or siCtrl for 48hr to knockdown PML expression. WDR4 or vector was overexpressed in A549 cells for 48hr. These four sets of cells were then subjected to microarray profiling using the Human OneArray microarray (version HOA6.1, GEO Platform GPL19137) from Phalanx Biotech Group. Comparison of transcriptomes from siPML/siCtrl and W4/vec in A549 cells
2016-07-04 | E-GEOD-83499 | biostudies-arrayexpress
Project description:Assess gene expression patterns upon HOXA9 ectopic expression in U87MG GBM cell line and hTERT/E6/E7 immortalized human astrocytes, and HOXA9 silencing in U251 and GBML18 GBM cell lines. U87MG and hTERT/E6/E7 were retrovirally-infected with an MSCV control vector (MSCV-Control) or with a construct containing the coding region of HOXA9 (MSCV-HOXA9), resulting in U87MG-Control, U87MG-HOXA9, hTERT/E6/E7-Control and hTERT/E6/E7-HOXA9 cell lines. GBML18 and U251 cells were transfected with HOXA9 gene-specific shRNA sequences (shHOXA9) or a non-efective shRNA (shControl) in pGFP-V-RS plasmid, resulting in U251-shControl, U251-shHOXA9, GBML18-shControl and GBML18-shHOXA9 cell lines. Four experimental replicates for HOXA9 overexpression cell lines, and three for HOXA9 silencing cell lines were performed.
2015-01-30 | E-GEOD-56517 | biostudies-arrayexpress
Project description:Pathogenic mycobacteria have the ability to survive within macrophages and persist inside granulomas composed of host immune cells. The complex host-pathogen interactions that determine the outcome of a mycobacterial infection process result in marked alterations of the host gene expression profile. Here we used the zebrafish model to investigate the specificity of the host response to infections with two mycobacterium strains that give distinct disease outcomes: an acute disease with early lethality or a chronic disease with granuloma formation, caused by Mycobacterium marinum strains Mma 20 and E11, respectively. We performed a microarray study of different stages of disease progression in adult zebrafish and found that the acute and the chronic strains evoked partially overlapping host transcriptome signatures, despite that they induce profoundly different disease phenotypes. Both strains affected many signaling cascades, including Wnt and Tlr pathways. Interestingly, the strongest differences were observed at the initial stage of the disease. The immediate response to the acute strain was characterized by higher expression of genes encoding MHC class I proteins, matrix metalloproteinases, transcription factors, cytokines and other common immune response proteins. In contrast, small GTPase and histone gene groups showed higher expression in response to the chronic strain. We also found that nearly 1,000 mycobacterium-responsive genes overlapped between the expression signatures of infected zebrafish adults and embryos at different stages of granuloma formation. Since adult zebrafish possess an adaptive immune system similar to mammals and zebrafish embryos rely solely on innate immunity, this overlap indicates a major contribution of the innate component of the immune system in the response to mycobacterium infection. Taken together, our comparison of the transcriptome responses involved in acute versus chronic infections and in the embryonic versus adult situation provides important new leads for investigating the mechanism of mycobacterial pathogenesis. Zebrafish were handled in compliance with the local animal welfare regulations and maintained according to standard protocols (http://ZFIN.org). Infection experiments were approved by the local animal welfare committee (DEC) of the VU University medical center and of Leiden Univeristy. Infection experiments with adult fish were performed on young males selected from a wild type laboratory-breeding colony and acclimated to their new environment for one week in a quarantine area. These fish were kept at 28ËC on a 12:12 h light/dark rhythm throughout the experiment. Groups of 30 fish, infected with the same dose and strain of mycobacteria, were kept in small fish tanks (10 l) with their own separate filtering system (Eheim Ecco). Zebrafish were inoculated intraperitoneally as previously described (Meijer et al., 2004) with approximately 10000 bacteria or with phosphate-buffered saline (PBS) as a control. For the acute infection study with E11 and Mma20 strains, 3 fish per group were sacrificed at 1 and 6 days post infection (dpi) and used for microarray analysis. For comparison with the end stage of chronic E11 infection we used RNA samples from our previously published chronic infection study (Meijer et al., 2005; control fish c2 and infected fish i2) and additional RNA samples (2 controls, 2 infected) from a similar infection experiment. All chronically infected fish showed overt signs of fish tuberculosis, including lethargy and skin ulcers. Histological examination of fish from the same experiments confirmed that the pathology of infected fish corresponded to fish tuberculosis (Van der Sar et al., 2004) and that no characteristics of the disease were present in the control fish. Infection experiments at the embryonic stage were performed using mixed egg clutches from different pairs of AB strain zebrafish. Embryos were grown at 28,5 -30 °C in egg water (60µg/ml Instant Ocean see salts) and for the duration of bacterial injections embryos were kept under anaesthesia in egg water containing 0.02% buffered 3-aminobenzoic acid ethyl ester (tricaine, Sigma). Embryos were staged at 28 hours post fertilization (hpf) by morphological critera (Kimmel et al.) and approximately 50 cfu of E11 bacteria were injected into the caudal vein close to the urogenital opening. As a control an equal volume of PBS was likewise injected. Infection experiments were carried out in triplicate on separate days and pools of 15-20 embryos were taken at 2, 24 and 120 hours post infection (hpi).
2010-05-15 | E-GEOD-15328 | biostudies-arrayexpress
Project description:In the present study we evaluated the miRNA expression profile of 31 high risk, stage 4 neuroblastoma patients. We compared miRNA expression profiles of 14 long-survivors (alive with an overall survival time > 36 months) and 17 short-survivors (dead of disease within 36 months from diagnosis. Deaths due to toxicity were censored).
2010-05-16 | E-GEOD-16444 | biostudies-arrayexpress
Project description:Circulating progesterone (P4) levels decline before the onset of parturition in most animals, but not in humans. This has led to the suggestion that there is functional withdrawal of P4 action at the myometrial level prior to labor onset. Mifepristone is widely used to induce human labour In this study, we aimed to establish and validate a model of human myometrial explants for the study of P4 action. Myometrial biopsies obtained at Caesearean section at term were dissected into explants after a portion was immediately snap-frozen (t=0). Transcriptomic comparison of paired explants and primary myometrial cells as well as the hTert immortalized myometrial cell line demonstrated that explants more closely resemble t=0. Biopsies obtained from non-laboring women at elective Caesarean section at term were divided into 3: (i) dissected and immediately snap-frozen (t=0), (ii) dissected into 3x3x3mm3myometrial explants and (iii) processed for primary cell culture. Explants, primary cells at passage 4 (the typical passage our group uses for experiments) and hTERT cells were cultured for a period of 30 hours without treatment. Total RNA was extracted and microarray analysis performed. 6 replicates were used for this study.
2016-05-30 | E-GEOD-77830 | biostudies-arrayexpress
Project description:Molecular profiling of effect of TNFα neutralization in contrast to anti-IL-17A or anti-IL-17F treatment for 28 days in lungs of M. tuberculosis infected C57BL/6 mice. Animals were treated once per week (starting day-1) with anti-mouse IL-17A or IL-17F antibodies (20 mg/kg i.p.), anti-mouse TNFα antibody (10 mg/kg), respective isotype control antibodies. Moreover, infected and non-infected TNFα-deficient mice were also analysed. Gene expression data revealed major changes of inflammatory and immune gene expression signatures 4 weeks post-infection (including host-pathogen interactions, macrophage recruitment, activation and polarization, host-anti-mycobacterial activities, immunomodulatory responses and extracellular matrix metallopeptidases) after TNFα blockade, while IL-17A or IL-17F neutralization elicited only mild changes of few genes without impaired host resistance four weeks after M. tuberculosis infection.
2016-12-02 | E-MTAB-5218 | biostudies-arrayexpress