Peripheral T-cell lymphoma unspecified (PTCL/U), the most common form of PTCL, displays heterogeneous morphology and phenotype, poor response to treatment, and dismal prognosis. We demonstrate that PTCL/U shows a gene expression profile clearly distinct from that of normal T-cells. Comparison with the profiles of purified T-cell subpopulations [CD4+, CD8+, resting (HLA-DR-), and activated (HLA-DR+)] reveals that PTCLs/U are most closely related to activated peripheral T-lymphocytes, either CD4+ or CD8+. Interestingly, the global gene expression profile cannot be surrogated by routine CD4/CD8 immunohistochemistry. When compared with normal T-cells, PTCLs/U display deregulation of functional programs often involved in tumorigenesis (e.g. apoptosis, proliferation, cell adhesion, and matrix remodeling). Products of deregulated genes can be detected in PTCLs/U by immunohistochemistry with an ectopic, paraphysiologic or stromal location. Among others, PTCLs/U aberrantly express PDGFRA, a tyrosine-kinase receptor, whose deregulation is often related to a malignant phenotype. Notably, both phosphorylation of PDGFRA and sensitivity of cultured PTCL cells to imatinib (as well as to an inhibitor of histone-deacetylase) are found. These results, which might be extended to other rarer PTCL categories, are provided with implications for tumor pathogenesis and clinical management.
Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets.
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View SamplesBurkitt lymphoma is the commonest cancer in children in Africa. We compared the gene expression profiles of African Burkitt lymphoma patients with those of cases presented in Western countries in both immunocompetent (sporadic Burkitt lymphoma) and HIV-infected patients (immunodeficiency associated Burkitt lymphoma).
Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes.
Specimen part
View SamplesIdentification of the determinants of PDGFRA activity in PTCL/NOS (Peripheral T-cell lymphoma/not otherwise specified) and to elucidate the biological consequences of its activation.
Platelet-derived growth factor alpha mediates the proliferation of peripheral T-cell lymphoma cells via an autocrine regulatory pathway.
Specimen part, Cell line
View SamplesA key event in the pathogenic process of prion diseases is the conversion of the cellular prion protein (PrPC) to an abnormal and protease-resistant isoform (PrPSc). Mice lacking PrP are resistant to prion infection, and down-regulation of PrPC during prion infection prevents neuronal loss and the progression to clinical disease. These results are suggestive of the potential beneficial effect of silencing PrPC during prion diseases. However, the silencing of a protein that is widely expressed throughout the CNS could be detrimental to brain homeostasis. The physiological role of PrPC remains still unclear, but several putative functions have been proposed. Among these, several lines of evidence support PrPC function in neuronal development and maintenance.
Developmental influence of the cellular prion protein on the gene expression profile in mouse hippocampus.
Specimen part
View SamplesMantle cell lymphoma (MCL) is an aggressive neoplasm with poor outcome. However, some patients have an indolent disease (iMCL) and may not require intensive treatment at initial diagnosis. Diagnostic criteria to recognize these patients are not available. We hypothesized that the analysis of the genetic and expression features of the tumors may help to identify patients with an indolent clinical evolution and provide biomarkers that could be used in the clinical setting.
Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma.
Disease, Disease stage
View SamplesIn order to gain insights into how PPARg regulates different facets of dendritic cell (DC) differentiation, we sought to identify PPARg regulated genes and gene networks in monocyte-derived dendritic cells using global gene expression profiling. We employed an exogenous ligand activation approach using a selective PPARg ligand (rosiglitazone abbreviated as RSG). In addition, we have defined culture conditions in which human serum (HS) induces PPARg activation via a yet uncharacterized endogenous mechanism. We also compared the gene expression profile of developing dendritic cells obtained from patients harboring dominant negative mutations of the PPARg receptor (C114R and C131Y).
PPARgamma regulates the function of human dendritic cells primarily by altering lipid metabolism.
Sex, Specimen part
View SamplesWe have looked for fusion genes in ovarian carcinomas. We combined previously known genomic aberrations, detected by karyotyping, and gene expression analysis. We found recurrent DPP9 gene expression deregulation with matching translocations. In additon, candidate fusion partner genes from the exon-level expression analysis were ranked according to deviating expression compared to the median of the sample set. The results were collated with data obtained from the RNA-seq analysis.
Involvement of DPP9 in gene fusions in serous ovarian carcinoma.
Specimen part
View SamplesStudy of the gene expression of T24 bladder cancer cells in response to hypericin-mediated photodynamic therapy in the absence or presence of the p38 MAPK inhibitor PD169316
Molecular effectors and modulators of hypericin-mediated cell death in bladder cancer cells.
Specimen part, Cell line, Compound
View SamplesChe-1 is a RNA Polymerase II binding protein involved in the regulation of gene transcription. We have observed that Che-1 depletion induces apoptosis in several cancer cells expressing mutated forms of p53. We used microarrays to investigate classes of genes regulated by Che-1 in one of these cell lines.
Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation.
Specimen part, Cell line
View SamplesBiofilms have been implicated in delayed wound healing, although the mechanisms by which biofilms impair wound healing are poorly understood. Many species of bacteria produce exotoxins and exoenzymes that may inhibit healing. In addition, oxygen consumption by biofilms, as well as responding leukocytes, may impede wound healing. In this study, we used oxygen microsensors to measure oxygen transects through in vitro-cultured biofilms, biofilms formed in vivo within scabs from a diabetic (db/db) mouse model, and ex vivo human chronic wound specimens. The results show that oxygen levels within mouse scabs had steep gradients that reached minima ranging from 17-72 mmHg on live mice and 6.4-1.1 mmHg on euthanized mice. The oxygen gradients in the mouse scabs were similar to those observed for clinical isolates cultured in vitro and for human ex vivo specimens. No oxygen gradients were observed for heat-killed mouse scabs, suggesting that active metabolism by the viable bacteria and host cells contributed to the reduced oxygen partial pressure of the scabs. To characterize the metabolic activities of the bacteria in the mouse scabs, we performed transcriptomics analyses of Pseudomonas aeruginosa biofilms associated with the db/db mice wounds using Affymetrix microarrays. The results demonstrated that the bacteria expressed genes for metabolic activities associated with cell growth. Interestingly, the transcriptome results indicated that the bacteria within the wounds also experienced oxygen-limitation stress. Among the bacterial genes that were expressed in vivo were genes associated with the Anr-mediated hypoxia-stress response. Other bacterial stress response genes highly expressed in vivo were genes associated with stationary-phase growth, osmotic stress, and RpoH-mediated heat shock stress. Overall, the results support the hypothesis that bacterial biofilms in chronic wounds promote chronicity by contributing to the maintenance of localized low oxygen tensions.
Microsensor and transcriptomic signatures of oxygen depletion in biofilms associated with chronic wounds.
Specimen part, Disease, Time
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