Hsp70 inhibition affects many signaling pathways. We established how these effects are translated into changes in gene expression.
Cancer cell responses to Hsp70 inhibitor JG-98: Comparison with Hsp90 inhibitors and finding synergistic drug combinations.
Cell line
View SamplesJG-98 reduces migration of macrophages. We assessed how this compound affects expression of genes associated with motility and migration. A number of motility/migration genes were significantly downregulated.
Anticancer Effects of Targeting Hsp70 in Tumor Stromal Cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Characterization of chemokine and chemokine receptor expression during Pneumocystis infection in healthy and immunodeficient mice.
Specimen part, Treatment
View SamplesFor both CD4 and micropajfe cell types, upregulated genes were primarily related to immune activation and proliferation, while down-regulated genes represented more diverse processes, including cell membranes, vasculature development, cell adhesion, and lipid-related metabolic processes.
Characterization of chemokine and chemokine receptor expression during Pneumocystis infection in healthy and immunodeficient mice.
Specimen part, Treatment
View SamplesFor both CD4 and micropajfe cell types, upregulated genes were primarily related to immune activation and proliferation, while down-regulated genes represented more diverse processes, including cell membranes, vasculature development, cell adhesion, and lipid-related metabolic processes.
Characterization of chemokine and chemokine receptor expression during Pneumocystis infection in healthy and immunodeficient mice.
Specimen part, Treatment
View SamplesRett syndrome (RTT, OMIM #312750) is a severe X-linked neurodevelopmental disorder linked to heterozygous de novo mutations in the MECP2 gene. MECP2 encodes methyl-CpG-binding protein 2 (MeCP2), which represses gene transcription by binding to 5-methylcytosine residues in symmetrically positioned CpG dinucleotides. The disorder is almost exclusively diagnosed in females, because males affected by the disease usually die perinatally due to severe encephalopathy. Direct MeCP2 target genes underlying the neuropathogenesis of RTT remain largely unknown.
FXYD1 is an MeCP2 target gene overexpressed in the brains of Rett syndrome patients and Mecp2-null mice.
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View SamplesIn wild-type mice, expression of chemokines that are ligands for Ccr2, Cxcr3, and Cxcr2 increased at days 32 to 41 post-infection, with a return to baseline by day 75. Concomitant increases were seen in Ccr2 and Cxcr3 but not in Cxcr2 expression. Induction of these same factors also occurred in CD40-ligand and CD40 knockout mice but only at a much later time-point, during uncontrolled Pneumocystis pneumonia (PCP). Expression of CD4 Th1 markers was increased in wild-type mice during clearance of infection. Ccr2 and Cx3cr1 knockout mice cleared Pneumocystis infection with kinetics similar to wild-type mice, and all animals developed anti-Pneumocystis antibodies. Upregulation of Ccr2 and Cxcr3 and their ligands supports an important role for T helper cells and mononuclear phagocytes in the clearance of Pneumocystis infection. However, based on the current and prior studies, no single chemokine receptor appears to be critical to the clearance of Pneumocystis.
Characterization of chemokine and chemokine receptor expression during Pneumocystis infection in healthy and immunodeficient mice.
Specimen part, Treatment
View SamplesMicroRNAs (miRNAs) represent a class of small non-coding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Emerging evidence suggests the potential involvement of altered regulation of miRNA in the pathogenesis of cancers, and these genes are thought to function as both tumor suppressors and oncogenes. Using microRNA microarrays, we identify several miRNAs aberrantly expressed in human ovarian cancer tissues and cell lines. miR-221 stands out as a highly elevated miRNA in ovarian cancer, while miR-21 and several members of the let-7 family are found downregulated. Public databases were used to reveal potential targets for the highly differentially expressed miRNAs. In order to experimentally identify transcripts whose stability may be affected by the differentially expressed miRNAs, we transfected precursor miRNAs into human cancer cell lines and used oligonucleotide microarrays to examine changes in the mRNA levels.
MicroRNA expression and identification of putative miRNA targets in ovarian cancer.
Sex
View Samples-glucans, which can activate innate immune responses, are a major component in the cell wall of the cyst form of Pneumocystis. In the current study we examined whether -1,3 glucans are masked by surface proteins in Pneumocystis, and what role -glucans play in Pneumocystis-associated inflammation. For 3 species, including P. jirovecii, which causes Pneumocystis pneumonia (PCP) in humans, P. carinii, and P. murina, -1,3 glucans were masked in most organisms, as demonstrated by increased exposure following trypsin treatment. Using Q-PCR and microarray techniques, we demonstrated in a mouse model of PCP that treatment with caspofungin, an inhibitor of -1,3 glucan synthesis, for 21 days, decreased expression of a broad panel of inflammatory markers, including IFN-, TNF-, IL-1, IL-6, and multiple chemokines/chemokine ligands. Thus, -glucans in Pneumocystis cysts are largely masked, which likely decreases innate immune activation; this mechanism presumably was developed for interactions with immunocompetent hosts, in whom organism loads are substantially lower. In immunosuppressed hosts with a high organism burden, organism death and release of glucans appears to be an important contributor to deleterious host inflammatory responses.
β-Glucans Are Masked but Contribute to Pulmonary Inflammation During Pneumocystis Pneumonia.
Specimen part, Treatment
View SamplesAnalysis of transcription response of undifferentiated human BE(2)-C neuronal cells to stimulation with purified antimycin A1a or unfractionated commercially available antimycin A (Sigma A8674).
Discovery of potent broad spectrum antivirals derived from marine actinobacteria.
Specimen part
View Samples