This SuperSeries is composed of the SubSeries listed below.
Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages.
Sex, Specimen part
View SamplesThe aim of this study was to identify differential gene expression resulting from the inhibition of class IIa HDACs in the CD3+ or CD11b+ cells residing in MMTV-PyMT tumors.
Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages.
Sex, Specimen part
View SamplesThe aim of this study was to identify differential gene expression resulting from the inhibition of class IIa HDACs in the CD3+ or CD11b+ cells residing in MMTV-PyMT tumors.
Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages.
Sex, Specimen part
View SamplesThe human C-type lectin Reg3a (HIP/PAP) is an antimicrobial peptide that kills Gram-positive bacteria. Reg3a preserves gut microbiota homeostasis, reinforces intestinal barrier function and thereby helps to fight induced colitis in mice.
Enteric Delivery of Regenerating Family Member 3 alpha Alters the Intestinal Microbiota and Controls Inflammation in Mice With Colitis.
Specimen part, Treatment
View SamplesrGal1 (recombinant Galectin-1) vs non treated (Ctrl) pancreatic cancer cell line RWP-1
Targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor-stroma crosstalk.
Specimen part, Cell line
View SamplesEffective therapies for non-small cell lung cancer (NSCLC) remain challenging despite an increasingly comprehensive understanding of somatically altered oncogenic pathways. It is now clear that therapeutic agents with potential to impact the tumor immune microenvironment potentiate immune-orchestrated therapeutic benefit. Herein we evaluated the immunoregulatory properties of histone deacetylase (HDAC) and bromodomain inhibitors, two classes of drugs that modulate the epigenome, with a focus on key cell subsets that are engaged in an immune response. By evaluating human peripheral blood and NSCLC tumors, we show that the selective HDAC6 inhibitor ricolinostat promotes phenotypic changes that support enhanced T cell activation and improved function of antigen presenting cells. The bromodomain inhibitor JQ1 attenuated CD4+Foxp3+ T regulatory cell suppressive function and synergized with ricolinostat to facilitate immune-mediated tumor growth arrest, leading to prolonged survival of mice with lung adenocarcinomas. Collectively, our findings highlight the immunomodulatory effects of two epigenetic modifiers that, together, promote T cell-mediated anti-tumor immunity and demonstrate their therapeutic potential for treatment of NSCLC. Overall design: Single-cell comparison of vehicle (control) and HDAC inhibitor (ricolinostat)-treated tumor infiltrating T cells and macrophages
Synergistic Immunostimulatory Effects and Therapeutic Benefit of Combined Histone Deacetylase and Bromodomain Inhibition in Non-Small Cell Lung Cancer.
Specimen part, Cell line, Treatment, Subject
View SamplesEnzalutamide (formerly MDV3100 and available commercially as Xtandi), a novel androgen receptor (AR) signaling inhibitor, blocks the growth of castration-resistant prostate cancer (CRPC) in cellular model systems and was shown in a clinical study to increase survival in patients with metastatic CRPC. Enzalutamide inhibits multiple steps of AR signaling: (1) binding of androgens to AR, (2) AR nuclear translocation, and (3) association of AR with DNA.
Enzalutamide, an androgen receptor signaling inhibitor, induces tumor regression in a mouse model of castration-resistant prostate cancer.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Environmentally induced epigenetic transgenerational inheritance of altered Sertoli cell transcriptome and epigenome: molecular etiology of male infertility.
Sex, Age, Specimen part, Treatment
View SamplesEnvironmental toxicants have been shown to induce the epigenetic transgenerational inheritance of adult onset disease, including testis disease and male infertility. The exposure of a gestating female during the period of gonadal sex determination has been shown to promote sperm epimutations, differential DNA methylation regions (DMR), that transmit transgenerational disease to subsequent generations. The current study was designed to determine the impact of an altered sperm epigenome on the subsequent development of an adult somatic cell (Sertoli cell) that influences the onset of a specific disease (male infertility). A gestating female rat (F0 generation) was exposed to the agriculture fungicide vinclozolin during gonadal sex determination and then the subsequent F3 generation progeny used for the isolation of Sertoli cells and assessment of testis disease. As previously observed, a spermatogenic cell apoptosis was observed. The Sertoli cells that provide the physical and nutritional support for the spermatogenic cells were isolated and alterations in gene expression examined. Over 400 genes were differentially expressed in the F3 generation control versus vinclozolin lineage Sertoli cells. A number of specific signaling pathways and cellular processes were identified to be transgenerationally altered. One of the key metabolic processes affected was pyruvate/lactate production that is directly linked to spermatogenic cell viability. The Sertoli cell epigenome was also altered with over 100 promoter differential DNA methylation regions (DMR) modified in the vinclozolin F3 generation Sertoli cell. The genomic features and overlap with the sperm DMR were investigated. Observations demonstrate that the transgenerational sperm epigenetic alterations subsequently alters the development of a specific somatic cell (Sertoli cell) epigenome and transcriptome that then has a role in the adult onset disease (male infertility). The environmentally induced epigenetic transgenerational inheritance of testis disease appears to be a component of the molecular etiology of male infertility.
Environmentally induced epigenetic transgenerational inheritance of altered Sertoli cell transcriptome and epigenome: molecular etiology of male infertility.
Sex, Age, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Environmentally induced transgenerational epigenetic reprogramming of primordial germ cells and the subsequent germ line.
Sex, Specimen part, Treatment, Time
View Samples