This SuperSeries is composed of the SubSeries listed below.
BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor.
Specimen part, Subject
View SamplesBromodomain and extra-terminal (BET) family proteins are key regulators of gene expression in cancer. Herein, we utilize BRD4 profiling to identify critical pathways involved in pathogenesis of chronic lymphocytic leukemia (CLL). BRD4 is over-expressed in CLL and is enriched proximal to genes up-regulated or de novo expressed in CLL with known function in disease pathogenesis and progression. These genes, including key members of the BCR signaling pathway, provide rationale for this therapeutic approach to identify new targets in alternative types of cancer. Additionally, we describe PLX51107, a structurally distinct BET inhibitor with novel in vitro and in vivo pharmacologic properties that emulates or exceeds the efficacy of BCR signaling agents in pre-clinical models of CLL. Herein, the discovery of the involvement of BRD4 in the core CLL transcriptional program provides a compelling rationale for clinical investigation of PLX51107 as epigenetic therapy in CLL and application of BRD4 profiling in other cancers.
BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor.
Specimen part, Subject
View SamplesWe used global gene expression profiles from human B-cell cell lines to generate gene expression signatures for prediction of response to the drugs cyclophosphamide, doxorubicin or vincristine. The signatures were validated in two publicly available clinical cohorts.
Predicting response to multidrug regimens in cancer patients using cell line experiments and regularised regression models.
Disease, Cell line
View SamplesThe pancreatic beta cells are the only cells that can produce insulin in response to prevailing glycemia. The development of beta cells was found to be depending on the activity of a complex genetic network. Overexpression of transcriptional factor MafK in beta cells have resulted in impairment of thier functions and suppressed insulin secretion and increased the severity of beta cell loss resulting in an overt diabetes.
β-Cell-Specific Mafk Overexpression Impairs Pancreatic Endocrine Cell Development.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Molecular classification of tissue from a transformed non-Hogkin's lymphoma case with unexpected long-time remission.
Sex, Specimen part
View SamplesComparison of gene expression profiles from diagnostic samples of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) to a patient case withsamples of primary and relapsed transformed FL
Molecular classification of tissue from a transformed non-Hogkin's lymphoma case with unexpected long-time remission.
Specimen part
View SamplesThe objective of this study was to make use of gene expression signatures and functional assays to delineate differences between various intestinal colon carcinoma cell lines and normal intestinal epithelium to assess their appropriateness as a tumor model or for drug absorption studies.
Defining new criteria for selection of cell-based intestinal models using publicly available databases.
Specimen part, Cell line
View SamplesThe goal of this study is to simultaneously interrogate host and parasite gene expression programs in human macrophages infected with the intracellular parasites from the genus Leishmania. We conducted high-resolution sequencing of the transcriptomes of human macrophages infected with Leishmania spp. using an RNA-seq approach. An array of computational tools was applied to map reads to the Leishmania and human genomes and reconstruct full-length transcripts. mRNA abundance was determined for Leishmania and human genes at various time points post-infection, enabling us to identify co-expression patterns that correlate with the biology of the parasite and to obtain a preliminary analysis of the dynamic nature of parasite and host cell gene expression programs in the context of infection. This study provides a solid framework for future functional and genomic studies of leishmaniasis as well as intracellular pathogenesis in general.
Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures.
No sample metadata fields
View SamplesWe conducted a preliminary investigation to determine whether ethanol-induced alterations in placental gene expression may have some utility as a diagnostic indicator of maternal drinking during pregnancy as well as a prognostic indicator of risk for adverse neurobehavioral outcomes in affected offspring.
Effects of moderate drinking during pregnancy on placental gene expression.
Specimen part
View SamplesMacrophages readily change their phenotype in response to exogenous stimuli. In this work, macrophages were stimulated under a variety of experimental conditions, and alterations in mRNA levels were analyzed. We identified three transcriptionally related populations of macrophages with immunoregulatory activity. They were generated by stimulating cells with TLR ligands, in the presence of three different “reprogramming” signals; high density immune complexes (IC), prostaglandin E2 (PGE2), or adenosine (Ado). All three of these cell populations produced higher levels of transcripts for IL-10, and growth and angiogenic factors. They also secreted reduced levels of inflammatory cytokines IL-1Beta, IL-6, and IL-12. All three macrophage phenotypes could partially rescue mice from lethal endotoxemia, and therefore we consider each to have immunoregulatory activity. This immunoregulatory activity occurred equally well in macrophages from stat6-deficient mice. The lack of STAT6 did not affect macrophages’ ability to reciprocally change cytokine production or to rescue mice from lethal endotoxemia. Furthermore, treatment of macrophages with IL-4 failed to induce similar phenotypic or transcriptional alterations. This work demonstrates that there are multiple ways to generate macrophages with immunoregulatory activity. These immunoregulatory macrophages are transcriptionally and functionally related, and quite distinct from macrophages treated with IL-4.
The generation of macrophages with anti-inflammatory activity in the absence of STAT6 signaling.
No sample metadata fields
View Samples