Cdk4/6 inhibitors have shown to increase overall survival in hormone-positive breast tumors, but whether other solid tumors could respond to these inhibitors has not yet defined. Here we show that Palbociclib (a Cdk4/6 specific inhibitor in clinic use) treatment exerts antiproliferative effects in vivo using a bladder cancer cell lines.
CDK4/6 Inhibitor as a Novel Therapeutic Approach for Advanced Bladder Cancer Independently of <i>RB1</i> Status.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epigenetic Networks Regulate the Transcriptional Program in Memory and Terminally Differentiated CD8+ T Cells.
Specimen part, Treatment
View SamplesEpigenetic mechanisms play a critical role during differentiation of T cells by contributing to the formation of stable and heritable transcriptional patterns. To further study the mechanisms of memory maintenance in CD8+ T cells, we performed genome-wide analysis of DNA methylation, histone marking (H3K9Ac and H3K9me3) and gene expression profiles in naive, effector memory (EM) and terminally differentiated memory (TEMRA) cells. Our results indicate that DNA demethylation and histone acetylation are coordinated to generate the transcriptional program associated with memory cells. Conversely, EM and TEMRA cells share a very similar epigenetic landscape. Nonetheless, the TEMRA transcriptional program predicts an innate immunity phenotype associated with genes never reported in these cells, including several mediators of NK cell activation (VAV3 and LYN) and a large array of NK receptors (KIR2DL3, KIR2DL4, KIR2DL1, KIR3DL1, KIR2DS5, etc.). In addition, we identified up to 161 genes that encode transcriptional regulators, some of unknown function in CD8+ T cells, that were differentially expressed in the course of differentiation. Overall, these results provide new insights into the regulatory networks involved in memory CD8+ T cell maintenance and T cell terminal differentiation.
Epigenetic Networks Regulate the Transcriptional Program in Memory and Terminally Differentiated CD8+ T Cells.
Specimen part
View SamplesEpigenetic mechanisms play a critical role during differentiation of T cells by contributing to the formation of stable and heritable transcriptional patterns. To further study the mechanisms of memory maintenance in CD8+ T cells, we performed genome-wide analysis of DNA methylation, histone marking (H3K9Ac and H3K9me3) and gene expression profiles in naive, effector memory (EM) and terminally differentiated memory (TEMRA) cells. Our results indicate that DNA demethylation and histone acetylation are coordinated to generate the transcriptional program associated with memory cells. Conversely, EM and TEMRA cells share a very similar epigenetic landscape. Nonetheless, the TEMRA transcriptional program predicts an innate immunity phenotype associated with genes never reported in these cells, including several mediators of NK cell activation (VAV3 and LYN) and a large array of NK receptors (KIR2DL3, KIR2DL4, KIR2DL1, KIR3DL1, KIR2DS5, etc.). In addition, we identified up to 161 genes that encode transcriptional regulators, some of unknown function in CD8+ T cells, that were differentially expressed in the course of differentiation. Overall, these results provide new insights into the regulatory networks involved in memory CD8+ T cell maintenance and T cell terminal differentiation.
Epigenetic Networks Regulate the Transcriptional Program in Memory and Terminally Differentiated CD8+ T Cells.
Specimen part, Treatment
View SamplesUstekinumab provides clinical benefit to psoriasis patients, but precise cellular and molecular changes underlying its therapeutic utility are not yet fully understood. To assess differences between ustekinumab responders vs. non responders in modulating specific inflammatory pathways and provide reference data for exploring molecular effects of next-generation interleukin(IL)-17 and IL-23-antagonists in psoriasis.
Modulation of inflammatory gene transcripts in psoriasis vulgaris: Differences between ustekinumab and etanercept.
Specimen part, Treatment, Subject, Time
View SamplesA gene expression profiling sub-study was conducted in which skin biopsy samples (n=192) were collected for RNA extraction and hybridization to microarrays from patients with moderate-to-severe psoriasis who participated in ACCEPT, an IRB-approved Phase 3, multicenter, randomized trial.
Modulation of inflammatory gene transcripts in psoriasis vulgaris: Differences between ustekinumab and etanercept.
Specimen part, Treatment, Subject, Time
View SamplesThis study was designed to address key questions concerning the use of alternative protein sources for animal feeds and addresses aspects such as their nutrient composition and impact on gut function, the immune system and systemic physiology. We used casein (CAS), partially delactosed whey powder (DWP), spray dried porcine plasma (SDPP), soybean meal (SBM), wheat gluten meal (WGM) and yellow meal worm (YMW) as protein sources.
Multi-Level Integration of Environmentally Perturbed Internal Phenotypes Reveals Key Points of Connectivity between Them.
Sex, Specimen part
View SamplesIn this study, we sought to determine how IL-17 and TNF influence normal human melanocytes, either alone, or with both cytokines together. We reveal a dichotomous effect of IL-17 and TNF, which not only elicit essential mitogenic cytokines but also suppress melanogenesis by down-regulating genes of melanogenesis pathway
IL-17 and TNF synergistically modulate cytokine expression while suppressing melanogenesis: potential relevance to psoriasis.
Specimen part, Treatment, Time
View SamplesComparison of gene expression profiles of the GL261 cell line (a murine glioma model) grown in duplicate in two different types of media. AC samples where grown in DMEM supplemented by 20% FBS, 5 U/ml pen/strep and 4 mM L-glutamine. NS samples were grown in DMEM/F12 (50/50) supplemented with 2 U/ml pen/strep, 1 ug/ml fungizone, 1x B27, 20 ng/ml bFGF, 20 ng/ml EGF, 20 ng/ml LIF and 5 ug/ml heparin. We have reason to believe the NS media enhances cell de-differentiation.
Neurospheres enriched in cancer stem-like cells are highly effective in eliciting a dendritic cell-mediated immune response against malignant gliomas.
Specimen part, Cell line
View SamplesRationale: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity among children. We postulate that severity of RSV infection is influenced in part by modulation of the host immune response by the local microbial ecosystem at the time of infection. Objectives: To define whether different nasopharyngeal microbiota profiles are associated with distinct host transcriptome profiles and severity in children with RSV infection. Methods: We analyzed the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy matched controls by 16S-rRNA sequencing. In parallel, we analyzed whole blood gene expression profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response and clinical disease severity. Measurements and Main results: We identified five nasopharyngeal microbiota profiles characterized by enrichment of H. influenzae, Streptococcus, Corynebacterium, Moraxella or S. aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus, and negatively associated with S. aureus abundance, independent of age. The host response to RSV was defined by overexpression of interferon-related genes, and this was independent of the microbiota composition. On the other hand, transcriptome profiles of RSV infected children with H. influenzae and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to toll-like receptor-signaling and neutrophil activation and were more frequently hospitalized Conclusions: Our data suggest an immunomodulatory role for the resident nasopharyngeal microbial community early in RSV infection, potentially affecting RSV disease severity.
Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection.
Sex, Specimen part, Disease, Race
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