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accession-icon GSE78932
Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs with in vivo activity in hematological malignancies
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 2.0 ST Array (hugene20st), Illumina HiSeq 2000

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies.

Sample Metadata Fields

Cell line, Treatment

View Samples
accession-icon GSE78517
Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs with in vivo activity in hematological malignancies [array]
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000, Affymetrix Human Gene 2.0 ST Array (hugene20st)

Description

The indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favored development of epigenetic drugs. In this study, we have design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of hematological neoplasia (Acute Myeloid Leukemia-AML, Acute Lymphoblastic Leukemia-ALL and Diffuse Large B-cell Lymphoma-DLBCL) with the lead compound CM-272, inhibited cell proliferation and promoted apoptosis, inducing interferon stimulated genes and immunogenic cell death. CM-272 significantly prolonged survival of AML, ALL and DLBCL xenogeneic models. Our results represent the discovery of first-in-class dual inhibitors of G9a/DNMTs and establish this chemical series, as a promising therapeutic tool for unmet needs in hematological tumors.

Publication Title

Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies.

Sample Metadata Fields

Cell line, Treatment

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accession-icon GSE48463
Translation control of TAK1 mRNA by hnRNP K modulates LPS-induced macrophage activation
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Macrophage activation by bacterial lipopolysaccharides (LPS) is induced through Toll-like receptor 4 (TLR4). The synthesis and activity of TLR4 downstream signalling molecules modulates the expression of pro- and anti-inflammatory cytokines. To address the impact of post-transcriptional regulation on that process, we performed RIP-Chip analysis. Differential association of mRNAs with heterogeneous ribonucleoprotein K (hnRNP K), an mRNA-specific translational regulator in differentiating haematopoietic cells, was studied in non-induced and LPS-activated macrophages. Analysis of interactions affected by LPS revealed an enrichment of mRNAs encoding TLR4 downstream kinases and their modulators. We focused on transforming growth factor activated kinase-1 (TAK1), a central player in TLR4 signalling. HnRNP K interacts specifically with a sequence in the TAK1 mRNA 3' UTR in vitro. Silencing of hnRNP K does not affect TAK1 mRNA synthesis and stability, but enhances TAK1 mRNA translation, resulting in elevated TNF-alpha, IL-1beta and IL-10 mRNA expression. Our data suggest that the hnRNP K-3' UTR complex inhibits TAK1 mRNA translation in non-induced macrophages. LPS-dependent TLR4 activation abrogates translational repression and newly synthesised TAK1 initiates the inflammatory response of macrophages.

Publication Title

Translation control of TAK1 mRNA by hnRNP K modulates LPS-induced macrophage activation.

Sample Metadata Fields

Specimen part, Cell line, Treatment

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accession-icon GSE10038
Upregulation of Expression of Matrix Metalloproteinases in Alveolar Macrophages of HIV1+ Smokers with Early Emphysema
  • organism-icon Homo sapiens
  • sample-icon 11 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

HIV1+ smokers develop emphysema at an earlier age and with a higher incidence than HIV1- smokers. Based on the knowledge that human alveolar macrophages (AM) are capable of producing proteases that degrade extracellular matrix components, we hypothesized that upregulation of AM matrix metalloproteinases may be associated with the emphysema of HIV1+ smokers. To test this hypothesis, microarray analysis was used to screen which MMP genes were expressed by AM isolated by bronchoalveolar lavage (BAL) of HIV1+ smokers with early emphysema. For each of the MMP genes observed to be expressed (MMP-1, -2, -7, -9, -10, -12 and -14), TaqMan PCR was used to quantify the relative expression in AM from 4 groups of individuals: HIV1 healthy nonsmokers, HIV1- healthy smokers, HIV1- smokers with early emphysema and HIV1+ smokers with early emphysema. Strikingly, while AM gene expression of MMPs was higher in HIV1- individuals with emphysema in comparison with HIV1- healthy smokers, for the majority of the MMPs (-1, -7, -9, -10, -12), AM expression from HIV1+ smokers with early emphysema was significantly higher than HIV1- smokers with early emphysema. Consistent with these observations, HIV1+ individuals with early emphysema had higher levels of epithelial lining fluid MMPs (-2, -7, -9,-12) than the 3 HIV1 groups. Interestingly, the active forms of MMP-2, -9 and -12 were detected in epithelial lining fluid from HIV1+ individuals with early emphysema, but not in any of the other groups. Considering that the substrate specificity of the upregulated AM MMPs includes collagenases, gelatinases, matrilysins and elastase, these data suggest that upregulated AM MMP genes and activation of MMP proteins may contribute to the emphysema of HIV1+ individuals who smoke.

Publication Title

Up-regulation of alveolar macrophage matrix metalloproteinases in HIV1(+) smokers with early emphysema.

Sample Metadata Fields

Sex, Age

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accession-icon GSE89846
Master Regulators of oncogenic KRAS response in Pancreatic Cancer
  • organism-icon Mus musculus
  • sample-icon 24 Downloadable Samples
  • Technology Badge IconIllumina MouseWG-6 v2.0 R2 expression beadchip

Description

We derived a transcriptional signature of oncogenic KRAS by using the KF508 murine pancreatic ductal cell line with an inducible Lox-Stop-Lox (LSL) cassette in front of the KRASG12D oncogene to regulate transcription. This dataset allowed us to study the differential expression profile after oncogenic KRAS induction in mouse.

Publication Title

Master Regulators of Oncogenic KRAS Response in Pancreatic Cancer: An Integrative Network Biology Analysis.

Sample Metadata Fields

Cell line, Treatment

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accession-icon GSE28244
Expression profile of maizes stalk challenged with the corn borer Sesamia nonagrioides
  • organism-icon Zea mays
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Maize Genome Array (maize)

Description

Stalk borers are major pests for some of the most important crops in the world, such as maize or rice. Plant defense mechanisms against these herbivores have been poorly investigated. The maizes stalk responds to insect feeding activating defense genes including hormone biosynthetic-related or proteinase inhibitor transcripts. The most outstanding conclusion is that cells in the maizes stalk undergo cell wall fortification after corn borer tunneling.

Publication Title

Inducible maize defense mechanisms against the corn borer Sesamia nonagrioides: a transcriptome and biochemical approach.

Sample Metadata Fields

Specimen part

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accession-icon GSE32285
Genome-wide analysis of lupus immune complex stimulation and how this response is regulated by C1q
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge IconIllumina HumanRef-8 v3.0 expression beadchip

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.

Sample Metadata Fields

Specimen part, Treatment, Subject

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accession-icon GSE32278
Genome-wide analysis of lupus immune complex stimulation of purified CD14+ monocytes and how this response is regulated by C1q
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge IconIllumina HumanRef-8 v3.0 expression beadchip

Description

The goal of this study was to determine what genes are up- and down-regulated in response to lupus immune complexes in purified CD14+ monocyte stimulations. Our results have shown that novel genes are induced by immune complexes but the response is less robust when using purified monocytes versus total PBMCs

Publication Title

Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.

Sample Metadata Fields

Specimen part, Treatment, Subject

View Samples
accession-icon GSE83456
The transcriptional signature of active tuberculosis reflects symptom status in extra-pulmonary and pulmonary tuberculosis
  • organism-icon Homo sapiens
  • sample-icon 202 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V4.0 expression beadchip

Description

Background: Mycobacterium tuberculosis infection is a leading cause of infectious death worldwide. Gene-expression microarray studies profiling the blood transcriptional response of tuberculosis (TB) patients have been undertaken in order to better understand the host immune response as well as to identify potential biomarkers of disease. To date most of these studies have focused on pulmonary TB patients with gene-expression profiles of extra-pulmonary TB patients yet to be compared to those of patients with pulmonary TB or sarcoidosis.

Publication Title

The Transcriptional Signature of Active Tuberculosis Reflects Symptom Status in Extra-Pulmonary and Pulmonary Tuberculosis.

Sample Metadata Fields

Sex, Age, Specimen part, Disease, Disease stage, Race

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accession-icon GSE13259
Comparisons of epithelial and mesenchymal murine breast tumor cell lines
  • organism-icon Mus musculus
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Epithelial tumor cells (E) underwent EMT in vivo in FVB/N mice generating mesenchymal tumors. Mesenchymal cell lines (M1-M4) were each derived from a different mouse. This study compares gene expression between these two different tumor types.

Publication Title

Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells.

Sample Metadata Fields

No sample metadata fields

View Samples
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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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