Growth of the drosophila eye imaginal discs is controlled by the activation of Notch in the dorsal-ventral boundary. Overexpression in the eye disc of the Notch ligand Delta together with lola and pipsqueak from the GS(2)88A8 line induces tumoral growth. We used microarray to analyze the expression profile of tumoral discs.
Imaginal discs secrete insulin-like peptide 8 to mediate plasticity of growth and maturation.
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View SamplesGain-of-function mutations in NOTCH1 are common in T-cell lymphoblastic leukemias making this receptor a promising target for drugs such as gamma-secretase inhibitors (GSI), which block a proteolytic cleavage required for NOTCH1 activation. However, the enthusiasm for these therapies has been tempered by tumor resistance and the paucity of information on the oncogenic programs regulated by oncogenic NOTCH1. Analysis of gene expression in GSI-responsive and GSI-resistant cell lines treated with Compound E identifies differential resopnses to GSI.
Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia.
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View SamplesGain-of-function mutations in NOTCH1 are common in T-cell lymphoblastic leukemias making this receptor a promising target for drugs such as gamma-secretase inhibitors, which block a proteolytic cleavage required for NOTCH1 activation. However, the enthusiasm for these therapies has been tempered by tumor resistance and the paucity of information on the oncogenic programs regulated by oncogenic NOTCH1. Here we show that NOTCH1 regulates PTEN expression and the activity of the PI3K-AKT signaling pathway in normal and leukemic T cells. Notch signaling and the PI3K-AKT pathway synergize in vivo in a Drosophila model of Notch-induced tumorigenesis, and mutational loss of PTEN is associated with increased glycolysis and resistance to NOTCH1 inhibition in human T-ALL. These findings identify the transcriptional regulation of PTEN and the control of cellular metabolism as key elements of the oncogenic program activated by NOTCH1 and provide the basis for the design of new therapeutic strategies for T-ALL.
Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia.
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View SamplesUnderstanding the underlying mechanisms of the well-established platelet hyporeactivity in neonates, would be of great relevance for both improving the clinical management of neonates, a population with a higher bleeding risk than adults (especially among sick and preterm infants), and getting new insights onto the regulatory mechanisms of platelet biology. Transcriptome analysis is a useful tool to identify mRNA signature affecting platelet function. However, human fetal/neonatal platelet transcriptome analysis has never been reported. Here, we used, for the first time, mRNA expression array to compare the platelet transcriptome changes during development. Microarray analysis was performed in pure platelet RNA obtained from adult and cord blood, using the same platform in two independent laboratories.
Comprehensive comparison of neonate and adult human platelet transcriptomes.
Specimen part
View SamplesThis study is part of previous epidemiologic project, including a population-based survey (Sao Paulo Ageing & Health study (SPAH Study). The data from this study was collected between 2015 to 2016 and involved elderly women (ages ≥65 yeas) living in the Butanta district, Sao Paulo. The purpose of the study was identification of association between transcriptome and the osteo metabolism diseases phenotype, like osteoporosis, vertebral fracture and coronary calcification.
Overexpression of SNTG2, TRAF3IP2, and ITGA6 transcripts is associated with osteoporotic vertebral fracture in elderly women from community.
Sex, Age
View SamplesWe used an inducible ShRNA system and microarrays to detail the global programme of gene expression underlying neuroblastoma differentiation upon CHAF1A silencing .
Histone chaperone CHAF1A inhibits differentiation and promotes aggressive neuroblastoma.
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View SamplesRecent data demonstrate that extracellular signals are transmitted through a network of proteins rather than hierarchical signaling pathways. This network model suggests why inhibition of a single component of a canonical pathway, even when targeting a mutationally activated driver of cancer, has insufficiently dramatic effects on the treatment of cancer. The biological outcome of signals propagated through a network is inherently more robust and resistant to inhibition of a single network component due to compensatory and redundant signaling events. In this study, we performed a functional chemical genetic screen analogous to synthetic lethal screening in yeast genetics to identify novel interactions between signaling inhibitors that would not be predicted based on our current understanding of signaling networks. We screened over 300 drug combinations in nine melanoma cell lines and have identified pairs of compounds that show synergistic cytotoxicity. Among the most robust and surprising results was synergy between sorafenib, a multi-kinase inhibitor with activity against Raf, and diclofenac, a non-steroidal anti-inflammatory drug (NSAID). This synergy did not correlate with the known RAS and BRAF mutational status of the melanoma cell lines. The NSAIDs celecoxib and ibuprofen could qualitatively substitute for diclofenac. Similarly, the MEK inhibitor PD325901 and the Raf inhibitor RAF265 could qualitatively substitute for sorafenib. These drug substitution experiments suggest that inhibition of cyclo-oxygenase and MAP kinase signaling are components of the observed synergistic cytotoxicity. Genome-wide expression profiling demonstrates synergy-specific down-regulation of survival-related genes. This study provides proof of principle that synthetic lethal screening can uncover novel functional drug combinations and suggests that the underlying signaling networks that control responses to targeted agents can vary substantially depending on unexplored components of the cell genotype.
Synthetic lethal screening with small-molecule inhibitors provides a pathway to rational combination therapies for melanoma.
Cell line, Treatment
View SamplesHeLa cells transfected to express KDELR1 and HeLa cells incubated with KDEL-Bodipy peptide
Control systems of membrane transport at the interface between the endoplasmic reticulum and the Golgi.
Cell line, Treatment
View SamplesInflammatory mediators play a role in the pathogenesis/progression of chronic heart failure (CHF). The aim of the present study was to identify diagnostic/prognostic markers and gene expression profiles of CHF vs control.
Gene expression profiles in peripheral blood mononuclear cells of chronic heart failure patients.
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View SamplesPhysical exercise training is a known protective factor against cardiovascular morbidity and mortality. Nevertheless, the underlying specific molecular mechanisms still remain uncompletely explored. To identify molecular mechanisms by which exercise training induces this favorable phenotype a genomic approach was used in an animal model of mild exercise previously demonstrated by our group to induce cardioprotection.
Gene expression profile of rat left ventricles reveals persisting changes following chronic mild exercise protocol: implications for cardioprotection.
No sample metadata fields
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