Accumulating data support the concept that ionizing radiation therapy (RT) has the potential to convert the tumor into an in situ, individualized vaccine; however this potential is rarely realized by RT alone. Transforming growth factor (TGF) is an immunosuppressive cytokine that is activated by RT and inhibits the antigen-presenting function of dendritic cells and the differentiation of effector CD8+ T cells. Here we tested the hypothesis that TGF hinders the ability of RT to promote anti-tumor immunity. Development of tumor-specific immunity was examined in a pre-clinical model of metastatic breast cancer.
TGFβ Is a Master Regulator of Radiation Therapy-Induced Antitumor Immunity.
Sex, Specimen part
View SamplesFanconi anemia (FA) is a rare inherited disease complicated by aplastic anemia. There is evidence that hematopoietic stem cells have lost self replicative capacity and undergo apoptosis when exposed to inhibitory cytokines including interferon gamma and tumor necrosis factor-alpha.
TLR8-dependent TNF-(alpha) overexpression in Fanconi anemia group C cells.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesRecent advances in multiple whole genome technologies provide unprecedented opportunities to profile epigenomic signatures in cancer cells. Previously we used a human gene promoter tiling microarray platform to identify genome-wide DNA methylation changes in a cell line model of breast cancer metastasis. Interestingly, the clustered nature of epigenetic targets that we identified, along with our concurrent karyotype analyses, have now led us to hypothesize that complex genomic alterations in cancer cells (deletions, translocations and ploidy) may be superimposed over promoter-specific methylation events that are responsible for gene-specific expression changes.
Multi-platform whole-genome microarray analyses refine the epigenetic signature of breast cancer metastasis with gene expression and copy number.
Cell line
View SamplesSelenate is chemically similar to sulfate and can be taken up and assimilated by plants via the same transporters and enzymes. In contrast to many other organisms, selenium (Se) has not been shown to be essential for higher plants. In excess, Se is toxic and restricts development. Both Se deficiency and toxicity pose problems worldwide. To obtain better insight into the effects of Se on plant metabolism and into plant mechanisms involved in Se tolerance, the transcriptome of Arabidopsis plants grown with or without selenate was studied, and Se-responsive genes identified. Roots and shoots exhibited different Se-related changes in gene regulation and metabolism. Many genes involved in sulfur (S) uptake and assimilation were upregulated. Accordingly, Se treatment enhanced sulfate levels in plants, but the quantity of organic S metabolites decreased. Transcripts regulating the synthesis and signaling of ethylene and jasmonic acid were also upregulated by Se. Selenate appeared to repress plant development, as suggested by the down-regulation of genes involved in cell wall synthesis and auxin-regulated proteins. The Se-responsive genes discovered in this study may help create plants that can better tolerate and accumulate Se, which may enhance the effectiveness of Se phytoremediation or serve as Se-fortified food.
Transcriptome analyses give insights into selenium-stress responses and selenium tolerance mechanisms in Arabidopsis.
No sample metadata fields
View SamplesEKLF is a Krppel-like transcription factor identified as a transcriptional activator and chromatin modifier in erythroid cells. EKLF-deficient (Eklf -/-) mice die at day 14.5 of gestation from severe anemia. In this study, we demonstrate that early progenitor cells fail to undergo terminal erythroid differention in Eklf -/- embryos. To discover potential EKLF target genes responsible for the failure of erythropoiesis, transcriptional profiling was performed with RNA from wild type and Eklf -/- early erythroid progenitor cells. These analyses identified significant perturbation of a network of genes involved in cell cycle regulation, with the critical regulator of the cell cycle, E2f2, at a hub. E2f2 mRNA and protein levels were markedly decreased in Eklf -/- early erythroid progenitor cells, which showed a delay in the G1-to-S-phase transition. Chromatin immunoprecipitation analysis demonstrated EKLF occupancy at the proximal E2f2 promoter in vivo. Consistent with the role of EKLF as a chromatin modifier, EKLF binding-sites in the E2f2 promoter were located in a region of EKLF-dependent DNase I sensitivity in early erythroid progenitor cells. We propose a model in which EKLF-dependent activation and modification of the E2f2 locus is required for cell cycle progression preceding terminal erythroid differentiation.
Failure of terminal erythroid differentiation in EKLF-deficient mice is associated with cell cycle perturbation and reduced expression of E2F2.
Age, Specimen part
View SamplesA fundamental issue in cell biology is how migratory cell behaviors are controlled by dynamically regulated cell adhesion.
Ovo1 links Wnt signaling with N-cadherin localization during neural crest migration.
Age, Specimen part
View SamplesWe found that amino acid transporter LHT1 was required for negatively regulating plant defence responses in addition to its physiological role in development and growth. In order to identify which defense pathways were involved in this process, we compared the expression profiles between wild type and lht1 mutant leaves without or with infection by Pseudomonas syringae pv. tomato DC3000 (Pst). In the lht1 mutant, except the changes in nitrogen metabolism-, cellular redox-, and photorespiration-associated gene expressions, the most drastic upregulations were found in the salicylic acid pathway-associated defense genes.
Amino acid homeostasis modulates salicylic acid-associated redox status and defense responses in Arabidopsis.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of a gene expression driven progression pathway in myxoid liposarcoma.
Sex, Age, Specimen part
View SamplesFUS-CHOP and EWS-CHOP balanced translocations characterize myxoid liposarcoma which encompasses myxoid (ML) and round cell (RC) variants initially believed to be distinct diseases. Currently, myxoid and RC liposarcoma are regarded to represent the well differentiated and the poorly differentiated ends, respectively, within spectrum of myxoid liposarcoma where the fusion proteins blocking lipogenic differentiation play a role in tumor initiation while molecular determinants associated to progression to RC remain poorly understood. Activation of AKT pathway sustained by PIK3CA and PTEN mutations and growth factor receptor signalling such as RET and IGF1R have been recently correlated with the increasing of aggressiveness and RC. Aim of the present study is to elucidate molecular events involved in driving round cell progression analyzing two small series of MLS selected to be representative of the two end of the gamut: the pure myxoid (0% of RC component) and RC with high cellular component (80%).
Identification of a gene expression driven progression pathway in myxoid liposarcoma.
Sex, Age, Specimen part
View SamplesMass populations of thyrocytes stably expressing wild type RET/PTC1 oncogene or RET/PTC1 carrying Y451F mutation and parental thyrocytes were used for hybridization on Affymetrix HG-U133A and HG-U133B chips. For each cell condition were generated two different targets (indicated as two different samples in the database, i.e. "Parental Thyrocytes" and "Parental Thyrocytes bis")for a total number of six samples. For the data analysis the two samples from the same condition (i.e. Parental thyrocytes) were considered as duplicates.
Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene.
Specimen part
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