Recently, attenuated Semliki Forest virus vector VA7 completely eliminated type I interferon (IFN) unresponsive human U87 glioma xenografts while IFN responsive mouse GL261 and CT-2A gliomas proved refractory to the oncolytic virotherapy. Here we describe in two clones of a well established Balb/c mouse tumor cell line, CT26 murine colon carcinoma, diametrically opposed IFN responsiveness and sensitivity to oncolytic virus. Both CT26WT and CT26LacZ clones secreted biologically active type I IFN in vitro upon infection but virus replication was self-limiting only in CT26WT cells. Total transcriptome sequencing (RNA-Seq) and western blotting experiments revealed that in sharp contrast to CT26LacZ cells, CT26WT cells had strong constitutive expression of 56 different genes associated with pattern recognition and type I interferon signaling pathways, spanning two reported anti-RNA virus gene signatures and22 genes that have been reported to have direct anti-Alphaviral activity. Correspondingly, only CT26LacZ tumors were infectable in vivo, resulting in rapid central necrosis of the tumors by 96 hours post infection and complete tumor eradication both in immunocompetent and in SCID mice. CT26LacZ tumor eradication by oncolysis induced 100% protective immunity against homologous CT26LacZ challenge but only 50% protection against heterologous CT26WT challenge, indicating LacZ immune dominance over shared antigens. We believe the two clone CT26 system described herein constitutes a challenging yet realistic model for clonally and immunologically heterogeneous cancer where a strong therapy efficacy bias toward sensitive tumor subpopulations might falsely predict therapeutic success on a broad patient scale highlighting the necessity of successful pre-screening for responsive tumors. Overall design: RNA-Seq in CT26 tumor cell line
Clonal variation in interferon response determines the outcome of oncolytic virotherapy in mouse CT26 colon carcinoma model.
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View SamplesAsbestos has been shown to cause chromosomal damage and DNA aberrations. The fiber is associated with many different lung diseases such as asbestosis, malignant mesothelioma, and lung cancer, but the disease-related processes are still largely unknown. Our aim was to identify specific gene expression profiles by using Affymetrix arrays, in human cell lines A549, Beas-2B, and MeT5A exposed to asbestos in a time-dependent manner. The hybridization data was analyzed using an algorithm specifically designed for clustering short time series expression data, a canonical correlation analysis (CCA) for identifying correlations between the cell lines, and a Gene Ontology (GO) analysis method for the identification of enriched differentially expressed biological processes.
Gene expression profiles in asbestos-exposed epithelial and mesothelial lung cell lines.
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View SamplesWe have investigated whether the early dissemination of tumor cells into bone marrow is associated with a specific molecular pattern in primary lung cancer
Genomic profiles associated with early micrometastasis in lung cancer: relevance of 4q deletion.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.
Age, Specimen part
View SamplesAnalysis of uterine microenvironment at gene expression level. The hypothesis tested in the present study was that Tregs orchestrated the immune reponse triggered in presence of embryo
Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.
Age, Specimen part
View SamplesAnalysis of B16 tumor microenvironment at gene expression level. The hypothesis tested in the present study was that Tregs orchastrated the immune reponse triggered in presence of tumors
Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.
Age, Specimen part
View SamplesIn the present study transcriptome and proteome of recombinant, xylose-utilising S. cerevisiae grown in aerobic batch cultures on xylose were compared with glucose-grown cells both in glucose repressed and derepressed states. The aim was to study at genome-wide level how signalling and carbon catabolite repression differed in cells grown on either glucose or xylose. The more detailed knowledge about is xylose sensed as a fermentable carbon source, capable of catabolite repression like glucose, or is it rather recognised as a non-fermentable carbon source is important in achieving understanding for further engineering this yeast for more efficient anaerobic fermentation of xylose.
Regulation of xylose metabolism in recombinant Saccharomyces cerevisiae.
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View SamplesAnalysis of uterine microenvironment at gene expression level. The hypothesis tested in the present study was that Tregs orchestrated the immune reponse triggered in presence of embryo.
Regulatory T Cells Orchestrate Similar Immune Evasion of Fetuses and Tumors in Mice.
Age, Specimen part
View SamplesIn industrial fermentations of Saccharomyces cerevisiae, transient changes in oxygen concentration commonly occur and it is important to understand the behaviour of cells during these changes. Saccharomyces cerevisiae CEN.PK113-1A was grown in glucose-limited chemostat culture with 1.0% and 20.9% O2 in the inlet gas (D= 0.10 /h, pH5, 30C). After steady state was achieved, oxygen was replaced with nitrogen and cultures were followed until new steady state was achieved. The overall responses to anaerobic conditions of cells initially in different conditions were very similar. Independent of initial culture conditions, transient downregulation of genes related to growth and cell proliferation, mitochondrial translation and protein import, and sulphate assimilation was seen. In addition, transient or permanent upregulation of genes related to protein degradation, and phosphate and amino acid uptake was observed in all cultures. However, only in the initially oxygen-limited cultures was a transient upregulation of genes related to fatty acid oxidation, peroxisomal biogenesis, oxidative phosphorylation, TCA cycle, response to oxidative stress, and pentose phosphate pathway observed. Furthermore, from the initially oxygen-limited conditions, a rapid response around the metabolites of upper glycolysis and the pentose phosphate pathway was seen, while from the initially fully aerobic conditions, a slower response around the pathways for utilisation of respiratory carbon sources was observed.
Transcriptional responses of Saccharomyces cerevisiae to shift from respiratory and respirofermentative to fully fermentative metabolism.
Time
View SamplesProteinases play a pivotal role in wound healing by degrading molecular barriers, regulating cell-matrix interactions and availability of bioactive molecules. Matrix metalloproteinase-13 (MMP-13, collagenase-3) is a wide spectrum proteinase. Its expression and function is linked to the growth and invasion of many epithelial cancers such as squamous cell carcinoma. Moreover, the physiologic expression of MMP-13 is associated e.g. to scarless healing of human fetal skin and adult gingival wounds. While MMP-13 is not found in the normally healing skin wounds in human adults, it is expressed in mouse skin during wound healing. Thus, mouse wound healing models can be utilized for studying the role of MMP-13 in the events of wound healing. As the processes such as the migration and proliferation of keratinocytes, angiogenesis, inflammation and activation of fibroblasts are components of wound repair as well as of cancer, many results received from wound healing studies are also adaptable to cancer research.
MMP-13 regulates growth of wound granulation tissue and modulates gene expression signatures involved in inflammation, proteolysis, and cell viability.
Time
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