Drug Synergy Screen and Network Modeling in Dedifferentiated Liposarcoma (DDLS) part 1
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Martin Miller
PROVIDER: E-GEOD-50749 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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2013-09-24 | E-GEOD-50751 | biostudies-arrayexpress
Project description:T cells receive numerous positive and negative signals during primary antigen encounter that control their proliferation and function, but how these signals are integrated to modulate T cell memory has not been fully characterized. In these studies, we demonstrate that combining seemingly opposite signals, CTLA-4 blockade and rapamycin-mediated mTOR inhibition, during in vivo T cell priming leads to both an increase in the frequency of memory CD8+ T cells and improved memory responses to tumors and bacterial challenges. This enhanced efficacy corresponds to increased early expansion and memory precursor differentiation of CD8+ T cells and increased mitochondrial biogenesis and spare respiratory capacity in memory CD8+ T cells in mice treated with anti-CTLA-4 and rapamycin during immunization. Collectively, these results reveal that mTOR inhibition cooperates with rather than antagonizes blockade of CTLA-4, promoting unrestrained effector function and proliferation and an optimal metabolic program for CD8+ T cell memory. Total RNA was isolated from FACS-sorted, antigen-specific CD8+T cells from different treatment conditions at 5 or 35 days after primary T cell activation
2015-01-31 | E-GEOD-63022 | biostudies-arrayexpress
Project description:Human and rat umbilical cord matrix mesenchymal stem cells (UCMSC) possess the ability to control the growth of breast carcinoma cells. Comparative analyses of two types of UCMSC suggest that rat UCMSC-dependent growth regulation is significantly stronger than that of human UCMSC. Their different tumoricidal abilities were clarified by analyzing gene expression profiles in the two types of UCMSC. Microarray analysis revealed differential gene expression between untreated naïve UCMSC and those co-cultured with species-matched breast carcinoma cells. The analyses screened 17 differentially expressed genes that are commonly detected in both human and rat UCMSC. The comparison between the two sets of gene expression profiles identified two tumor suppressor genes, adipose-differentiation related protein (ADRP) and follistatin (FST), that were specifically up-regulated in rat UCMSC, but down-regulated in human UCMSC when they were co-cultured with the corresponding species' breast carcinoma cells. Over-expression of FST, but not ADRP, in human UCMSC enhanced their ability to suppress the growth of MDA-231 cells. The growth of MDA-231 cells was also significantly lower when they were cultured in medium conditioned with FST, but not ADRP over-expressing human UCMSC. In the breast carcinoma lung metastasis model generated with MDA-231 cells, systemic treatment with FST-overexpressing human UCMSC significantly attenuated the tumor burden. These results suggest that FST may play an important role in exhibiting stronger tumoricidal ability in rat UCMSC than human UCMSC and also implies that human UCMSC can be transformed into stronger tumoricidal cells by enhancing tumor suppressor gene expression. Human UCMSC and MDA-231 breast carcinoma cells were cultured indirectly for 48 hours using Transwell culture dish. Naïve human UCMSC were cultured under same condition without the addition of carcinoma cells.
2015-08-06 | E-GEOD-64827 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-08-06 | E-GEOD-64839 | biostudies-arrayexpress
Project description:In this experiment, there are replicate measurements of gene expression in a group of similarly treated animals measured in such a way as to provide data for comparison of technical variation with biological variability. The data are twelve microarray measurements on each of six rats that were subject to the same control-group treatment. The twelve measurements encompass triplicate measures of RNA from the liver, from the kidney, and from two mixtures of both RNAs. IMPORTANT: 6C-1 and 1-6B1 are outlier because of poor cRNA yield. 4A-1 (low cRNA yield too) and 4D-1 seems to have been switched during processing. 2D1 and 5A3 were also mistake (samples picked from the wrong well in the original 96 plates) as they seems to cluster with B samples (75% liver-25% Kidney).
2008-09-18 | E-TABM-554 | biostudies-arrayexpress
Project description:Despite the enormous amounts of molecular, cellular, and clinical data that are increasingly available for many different types of cancer, it remains a challenge to integrate different dimensions of data to construct mechanistic models that can robustly distinguish key driver genes from passenger genes, predict tumor progression, and tailor therapies optimally for individual patients. We present an integrative biology approach to constructing and analyzing multiscale regulatory networks of breast cancer. We systematically uncover not only known and novel gene subnetworks (modules) linked to breast cancer, but also their key drivers, the majority of which are not transcription factors or signaling molecules. A number of independent lines of evidence support that the predicted key drivers play central roles in breast cancer biology. We predict and experimentally validate ARF1 as a key driver of breast tumor phenotypes, and then demonstrate the ARF1-controlled subnetwork is a novel regulator of intra- and inter- cellular vesicle dynamics involved in epithelial-mesenchymal transition (EMT). We aimed to study the underlying mechanism by which ARF1 has been predicted playing crucial role during carcinogenesis and metastasis. To attest the key function of ARF1 during epithelial mesenchymal transition (EMT), loss of function in vitro study by means of siRNA knockdown of ARF1 in MDA-MB-231 breast cancer cell line was designed. Genome-wide gene expression of nine ARF1 knockdown samples and three control samples were profiled by using the Illumina HumanHT-12 V4.0 expression beadchip platform.
2013-07-18 | E-GEOD-49005 | biostudies-arrayexpress
Project description:Astrocytes are key cells in brain aging, helping neurons to undertake healthy aging or otherwise letting them enter into a spiral of neurodegeneration. We aimed to characterize astrocytes cultured from senescence-accelerated prone 8 (SAMP8) mice, a mouse model of brain pathological aging, along with the effects of caloric restriction, the most effective rejuvenating treatment known so far. Analysis of the transcriptomic profiles of SAMP8 astrocytes cultured in control conditions and treated with caloric restriction serum was performed using mRNA microarrays. A decrease in mitochondrial and ribosome mRNA, which was restored by caloric restriction, confirmed the age-related profile of SAMP8 astrocytes and the benefits of caloric restriction. An amelioration of antioxidant and neurodegeneration-related path- ways confirmed the brain benefits of caloric restriction. Studies of oxidative stress and mitochondrial function demonstrated a reduction of oxidative damage and partial improvement of mito- chondria after caloric restriction. In summary, caloric restriction showed a significant tendency to normalize pathologically aged astrocytes through the activation of pathways that are protective against the age-related deterioration of brain physiology. Key words: astrocytes; caloric restriction; mitochondria; oxidative stress; RNA microarrays; SAMP8. Primary cultures enriched in astrocytes were obtained from cerebral cortical tissue from 2-day-old SAMP8 and SAMR1 mice. Astrocyte cultures were established and experiments were routinely carried out after 21 days in culture. Established astrocyte cultures of both SAMR1 and SAMP8 consisted of 85-90% astrocytes, 10-15% microglia and 0.1-1% oligodendroglia. Sera from rats subjected to ad libitum (AL) diet and to CR were obtained as described for the establishment of the CR in vitro model (de Cabo et al., 2003). Serum was heat inactivated at 56°C prior to use in astrocyte culture experiments. Treatment in vitro was performed by adding 10% volume CR or AL serum onto the astrocyte culture medium for 48 h, the cells were harvested and RNA was extracted for the microarray studies. Three biological replicates for each condition were done and RNA was extracted for the microarray studies. Please note that SAM models were developed from AKR/J by Kyoto University. Five litters with severe senescence were selected to further propagate and examine these characteristics. Litters that showed normal aging were selected as a senescence-resistant series (R-series). The genetic background of the SAM mice became suspect after the pathological findings were different from the AKR/J mouse. Each SAM model is genetically different. Each SAM colony was acquired by Harlan by Takeda Chemical Ltd. in 2002. And here is the link to the company site. http://www.harlan.com/products_and_services/research_models_and_services/research_models/sam_inbred_mice/samp8tahsd.hl
2015-06-23 | E-GEOD-60388 | biostudies-arrayexpress
Project description:Consistent and independently replicated laboratory evidence to support a causative relationship between environmental exposure to extremely low frequency electromagnetic fields (ELF-EMF) at power line frequencies and the associated increase in risk of childhood leukaemia has not been obtained. In particular, although gene expression responses have been reported in a wide variety of cells, none have emerged as robust, widely replicated effects. DNA microarrays facilitate comprehensive searches for changes in gene expression without a requirement to select candidate responsive genes. To determine if gene expression changes occur in white blood cells of volunteers exposed to an ELF-EMF, each of 17 pairs of male volunteers age 20-30 was subjected either to a 50 Hz EMF exposure of 62.0 ± 7.1 μT for 2 h or to a sham exposure (0.21 ± 0.05 μT) at the same time (11:00-13:00). The alternative regime for each volunteer was repeated on the following day and the two-day sequence was repeated 6 days later except that a null exposure (0.085 ± 0.01 μT) replaced the sham exposure. Five blood samples (10 ml) were collected at 2 h intervals from 9:00 to 17:00 with five additional samples during the exposure and sham or null exposure periods on each study day at 11.05, 11.10, 11.20, 11.40 and 12.20. RNA samples were pooled for the same time points on each study day for the 17 volunteers that were subjected to the ELF-EMF exposure/sham or null exposure sequence and were analysed on Illumina microarrays. Time courses for 16 mammalian genes previously reported to be responsive to ELF-EMF exposure, including immediate early genes, stress response, cell proliferation and apoptotic genes were examined in detail. No genes or gene sets significantly expressed on the arrays showed consistent response profiles to repeated ELF-EMF exposures. A stress response was detected as a transient increase in plasma cortisol at the onset of either exposure or sham exposure on the first study day. The cortisol response diminished progressively on subsequent exposures or sham exposures and was attributable to mild stress associated with the experimental protocol. The study design described in the summary gave a total of 40 pooled RNA samples (10 for each study day) using equal amounts of RNA from the 17 volunteers exposed to ELF-EMF on study days 1 and 3, a sham exposure on study day 2 and a null exposures on study day 4. The pooled sample from 11:00 on Day1 (immediately prior to ELF-EMF exposure) was used as a reference sample that was amplified and labelled 4 times with the other samples from each of the 4 study days (titled as replicates 1 to 4). Each replicate was hybridised twice (titled replicates a and b for each day ( e.g. 1a, 1b) to give a total of 8 arrays from the reference RNA sample (Sample names 2 and 41-47, i.e.GSM879110-GSM879117).
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Project description:Transcriptional profiling was used to characterize the immunologic networks in subjects with CVID who have inflammatory complications to identify clues as to pathogenesis and potentially better modes of treatment. CVID subjects who fulfilled the standard diagnostic criteria, including significantly decreased levels of IgG, IgA, and/or IgM and poor or absent specific antibody production were enrolled. They were classified into, with or without characteristic inflammatory complications, as previously designated (hematologic or organ-specific autoimmunity, biopsy-proven granulomatous disease, or interstitial lung disease, lymphoid hyperplasia/ with splenomegaly or gastrointestinal inflammatory disease). 59 patients were included in the training set and 21 healthy controls and for test set 32 patients and 15 healthy controls. Disease controls included 6 X-linked agammaglobulinemia (XLA) patients and 15 healthy controls were included. Blood was taken before the interval intravenous immune globulin (Ig) infusions, or between subcutaneous administrations. The blood was collected using Tempus tubes and processed for microarray analysis.
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