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Homo sapiens
10 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Standardization of MSC manufacturing is urgently needed to facilitate comparison of clinical trial results. Here, we compare gene expression of MSC generated by the adaptation of a proprietary method for isolation and cultivation of a specific umbilical cord tissue-derived population of Mesenchymal Stromal Cells (MSCs)
Publication Title
Towards an advanced therapy medicinal product based on mesenchymal stromal cells isolated from the umbilical cord tissue: quality and safety data.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 192 Downloadable Samples
NextSeq 500
Description
Effective 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
Publication Title
Synergistic Immunostimulatory Effects and Therapeutic Benefit of Combined Histone Deacetylase and Bromodomain Inhibition in Non-Small Cell Lung Cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 180 Downloadable Samples
- Illumina HiSeq 2000
Description
Background: Immune checkpoint blockade improves survival in a subset of patients with non-small cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. Methods: We performed comprehensive flow-cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC). Results: Cytometric profiling identified an immunologically “hot” cluster with abundant CD8+ T cells expressing high levels of the PD-1 and TIM-3, and an immunologically “cold” cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers. The “hot” cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function, and high PD-L1 expression by IHC. There was no correlation between immunophenotype and KRAS or EGFR mutation, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the “hot” cluster. Additionally, ~20% of cases had high B cell infiltrates with a subset producing IL-10. Conclusions: Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer. Background: Immune checkpoint blockade improves survival in a subset of patients with non-small cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. Methods: We performed comprehensive flow-cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC). Results: Cytometric profiling identified an immunologically “hot” cluster with abundant CD8+ T cells expressing high levels of the PD-1 and TIM-3, and an immunologically “cold” cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers. The “hot” cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function, and high PD-L1 expression by IHC. There was no correlation between immunophenotype and KRAS or EGFR mutation, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the “hot” cluster. Additionally, ~20% of cases had high B cell infiltrates with a subset producing IL-10. Conclusions: Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer. Overall design: Single-cell comparison of normal and tumor infiltrated B-cells.
Publication Title
Multiparametric profiling of non-small-cell lung cancers reveals distinct immunophenotypes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 91 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
Summary: The liver is the major site of gluconeogenesis, fat processing and distribution, as well as drug and xenobiotic metabolism. Altered gene expression in the liver is centrally invovled in both the immuosuppressive and the energetic actions of corticosteroids.
Publication Title
Modeling of corticosteroid pharmacogenomics in rat liver using gene microarrays.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 63 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
Summary: To identify distinct temporal patterns of mRNA expression in the kidney of rats following a bolus dose of the corticosteroid methylprednisolone.
Publication Title
Corticosteroid-regulated genes in rat kidney: mining time series array data.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE25612- Rattus norvegicus
- 54 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Circadian rhythms are oscillations with a periodicity of 24 hours that are controlled by an endogenous clock and are observed in virtually all aspects of mammalian function from expression of genes to complex physiological processes. The master clock is present in the suprachiasmatic nucleus (SCN) in the anterior part of the hypothalamus and controls peripheral clocks present in other parts of the body . Although much is known about the mechanism of the central clock in the SCN, the regulation of clocks present in peripheral tissues is still unclear. This study is designed to examine fluctuations in gene expression in lungs within the 24 hour circadian cycle in normal animals. The objectives of this study is to identify and analyze circadian oscillation in gene expression in lungs, and to identify the role of circadian regulation in coordinating the functioning of this dynamic organ.
Publication Title
Light-dark oscillations in the lung transcriptome: implications for lung homeostasis, repair, metabolism, disease, and drug action.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 51 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
The aim of this project is to identify distinct temporal patterns of RNA expression in the skeletal muscle of rats following a bolus dose of the corticosteroid methylprednisolone. 51 RG_U34A chips were used over 17 time points.
Publication Title
Temporal profiling of the transcriptional basis for the development of corticosteroid-induced insulin resistance in rat muscle.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 52 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Circadian rhythms are oscillations with a periodicity of 24 hours that are controlled by an endogenous clock and are observed in virtually all aspects of mammalian function from expression of genes to complex physiological processes. The master clock is present in the suprachiasmatic nucleus (SCN) in the anterior part of the hypothalamus and controls peripheral clocks present in other parts of the body. Although much is known about the mechanism of the central clock in the SCN, the regulation of clocks present in peripheral tissues is still unclear. This study is designed to examine fluctuations in gene expression in abdominal white adipose tissue within the 24 hour circadian cycle in normal animals. The objectives of this study is to identify and analyze circadian oscillation in gene expression in white adipose tissue, and to identify the role of circadian regulation in coordinating the functioning of this dynamic tissue.
Publication Title
Circadian variations in gene expression in rat abdominal adipose tissue and relationship to physiology.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 301 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene expression analysis of hepatic roles in cause and development of diabetes in Goto-Kakizaki rats.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 100 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The goals and objectives: To study Type 2 diabetes progression and the development of insulin resistance in two animal models with and without a high fat diet superimposed on these models. Background: Diabetes is a systemic metabolic imbalance involving multiple tissues/organs, and an early hallmark feature of this disease state is insulin resistance. Multifactorial interactions of genetics, prenatal environmental factors (fetal programming) and postnatal environmental factors (nutrition and activity) likely contribute to the diabetic phenotype.Animal models can serve as a valuable tool for studying diabetes disease progression and for identifying useful biomarkers of type 2 diabetes. Several inbred rodent models are available for diabetes related studies. The GK rat is an obvious choice among available inbred models as the genetic basis for this inheritable form of diabetes is polygenic (5), unlike most other inbred rodent models that exhibit single gene defects. Many of the characteristics of the GK rat mirror human diabetes (hyperglycemia, glucose intolerance, insulin resistance), although hyperlipidemia does not appear to be prominent in the GK rat. Due to its polygenic mode of inheritance and 100% penetrance, the GK rat may be a useful model for human diabetes. Induced animal models can also be useful in diabetes studies. One such model is metabolic syndrome resulting from experimentally induced fetal programming (produced by maternal malnutrition or by exposure to corticosteroids in the third trimester). Both in humans and animals, accumulating evidence suggests that alterations in the human fetal environment can result in permanent physiologic changes that manifest as increased incidence of adult onset pathology. Numerous epidemiological studies have forged a strong link between low birth weight and the development of metabolic syndrome in adulthood. From such observations has arisen the concept of fetal programming whereby exposure to some factor(s) during crucial stages in development can permanently alter or reset physiologic/metabolic functions. In the rat, exposure to corticosteroids during a window in third trimester gestation (CS programming) results in fetal growth retardation and insulin resistance in adult offspring. Genetic factors play a primarily role in the etiology of diabetes in the GK rat, whereas fetal environmental factors are causative in CS programming. (It should be noted that although altered fetal environmental effects, most likely stemming from maternal hyperglycemia, have been implicated to play some role in the decreased pancreatic B cell mass in GK rats, these effects occur earlier in gestation and therefore differ from programming by CS in late gestation.) A comparison of the development of insulin resistance in the GK rat with development in the CS programmed rat will provide insight into genetic and fetal environmental factors in disease development. Superimposing dietary alterations (i.e., high fat feeding) (11) on both animal models may aid in the dissection of multiple interacting factors (genetic, fetal environmental factors, postnatal environmental factors) on the development and progression of insulin resistance and type 2 diabetes. Such studies may also aid in the identification of useful biomarkers for insulin resistance and type 2 diabetes in humans.
Publication Title
Gene expression analysis of hepatic roles in cause and development of diabetes in Goto-Kakizaki rats.
Sample Metadata Fields
No sample metadata fields
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