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GSE39671
Homo sapiens
124 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The clinical course of patients with chronic lymphocytic leukemia (CLL) is heterogeneous. Several prognostic factors have been identified that can stratify patients into groups that differ in their relative tendency for disease progression and/or survival. Here, we pursued a subnetwork-based analysis of gene expression profiles to discriminate between groups of patients with disparate risks for CLL progression.
Publication Title
Subnetwork-based analysis of chronic lymphocytic leukemia identifies pathways that associate with disease progression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 31 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Inflammation has pleiotropic effects on carcinogenesis and tumor progression. Signaling through the adaptor protein MyD88 promotes carcinogenesis in several chemically induced cancer models. Interestingly, we observed a protective role for MyD88 in the development of AOM/DSS colitis-associated cancer. The inability of Myd88-/- mice to heal ulcers generated upon injury creates an inflammatory environment that increases the frequency of mutations and results in a dramatic increase in adenoma formation and cancer progression. Susceptibility to colitis development and enhanced polyp formation were also observed in Il18-/- mice upon AOM/DSS treatment, suggesting that the phenotype of MyD88 knockouts is in part due to their inability to signal through the IL-18 receptor. This study revealed a previously unknown level of complexity surrounding MyD88 activities downstream of different receptors that differentially impact tissue homeostasis and carcinogenesis.
Publication Title
MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 25 Downloadable Samples
Illumina HiSeq 2500
Description
RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a fatal disease with overtly scarred peripheral and basilar lung regions and macroscopically unaffected central lung areas. OBJECTIVES: To gain better insight into IPF pathobiology by comparing transcriptomic profiles of normal-appearing and scarred regions of IPF lung. METHODS: Lung tissue samples from macroscopically unaffected (normal-appearing, IPFn) and scarred (IPFs) regions of explanted IPF lungs were analyzed by RNASeq and compared with healthy control (HC) lung tissues. RT-qPCR and immunohistochemistry were used to confirm selected findings. MEASUREMENTS AND RESULTS: Numerous previously reported IPF-associated gene expression disturbances as well as additional differentially expressed mRNAs were observed. There were profound transcriptomic changes in IPFn compared with HC tissues, which included elevated expression of extracellular matrix-, immunity- and inflammation-related mRNAs. The magnitude and statistical significance of these changes were comparable or greater than those in the IPFs-to-HC comparison. When directly compared with IPFn, IPFs tissues demonstrated elevated expression of epithelial mucociliary mRNAs. Compared with HC, both IPFn and IPFs tissues demonstrated reduced expression of mRNAs related to solute carrier membrane transport and metabolic processes. Primary fibroblast cultures from IPFn and IPFs tissues were transcriptomically identical. CONCLUSIONS: Macroscopically normal-appearing IPF tissues demonstrate profound disease activity and substantially similar transcriptomic profiles to scarred areas. Differences between these tissues are due to cell types other than fibroblasts and notably include enhanced expression of mucociliary genes in scarred areas. Deranged epithelial homeostasis or possibly non-transcriptomic factors may thus explain the marked architectural differences between normal-appearing and terminally scarred lung in end-stage IPF. Overall design: RNASeq of 26 lung tissue samples from patients with IPF, including affected and unaffected areas of the lung, and from healthy controls
Publication Title
Transcriptomic evidence of immune activation in macroscopically normal-appearing and scarred lung tissues in idiopathic pulmonary fibrosis.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Analysis of cervical carcinomas and cervical cell lines privides insight into gene expression profiling in mexican women
Publication Title
Krüppel Like Factors Family Expression in Cervical Cancer Cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The gut microbiota influences both local and systemic inflammation. Inflammation contributes to development, progression and treatment of cancer, but it remains unclear whether commensal bacteria affect inflammation in the sterile tumor microenvironment. Here we show that disruption of the microbiota impairs the response of subcutaneous tumors to CpG-oligonucleotide immunotherapy and platinum chemotherapy. In antibiotic-treated or germ-free mice, tumor-infiltrating myeloid-derived cells responded poorly to therapy, resulting in lower cytokine production and tumor necrosis after CpG-oligonucleotide treatment, and deficient production of reactive oxygen species and cytotoxicity following chemotherapy. Thus, optimal responses to cancer therapy require an intact commensal microbiota that mediates its effects by modulating myeloid-derived cell functions in the tumor microenvironment. These findings underscore the importance of the microbiota in the outcome of disease treatment.
Publication Title
Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
The eukaryotic genome is organized in a three-dimensional structure called chromatin, constituted by DNA and associated proteins, the majority of which are histones. Post-translational modifications of histone proteins greatly influence chromatin structure and regulate many DNA-based biological processes. Methylation of lysine 36 of histone 3 (H3K36) is a post-translational modification functionally relevant during early steps of DNA damage repair. Here, we show that the JMJD-5 regulates H3K36 di-methylation and it is required at late stages of double strand break repair mediated by homologous recombination. Loss of jmjd-5 results in hypersensitivity to ionizing radiation and in meiotic defects, and it is associated with aberrant retention of RAD-51 at sites of double strand breaks. Analyses of jmjd-5 genetic interactions with genes required for resolving recombination intermediates (rtel-1) or promoting the resolution of RAD-51 double stranded DNA filaments (rfs-1 and helq-1) suggest that jmjd-5 prevents the formation of stalled postsynaptic recombination intermediates and favors RAD-51 removal. As these phenotypes are all recapitulated by a catalytically inactive jmjd-5 mutant, we propose a novel role for H3K36me2 regulation during late steps of homologous recombination critical to preserve genome integrity. Overall design: RNA sequencing of N2 and jmjd-5(tm3735) at 20C and 25C at generation 1 (G1) and generation 6 (G6)
Publication Title
JMJD-5/KDM8 regulates H3K36me2 and is required for late steps of homologous recombination and genome integrity.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Background: Cancer stem cells are presumed to have virtually unlimited proliferative and self-renewal abilities and to be highly resistant to chemotherapy, a feature that is associated with overexpression of ATP-binding cassette transporters. We investigated whether prolonged continuous selection of cells for drug resistance enriches cultures for cancer stem-like cells.
Publication Title
Prolonged drug selection of breast cancer cells and enrichment of cancer stem cell characteristics.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
FOXO transcription factors control cellular formation of reactive oxygen species (ROS), which critically contribute to cell survival and cell death in neuroblastoma. Here, we report that C10orf10, also named Decidual Protein induced by Progesterone (DEPP), is a direct transcriptional target of FOXO3 in human neuroblastoma. As FOXO3-mediated apoptosis involves a biphasic ROS accumulation, we analyzed cellular ROS levels in DEPP-knockdown cells by live-cell imaging. Knockdown of DEPP prevented the primary and secondary ROS accumulation during FOXO3 activation and attenuates FOXO3-induced apoptosis, whereas its overexpression raises cellular ROS levels and sensitizes to cell death. In neuronal cells, cellular steady state ROS are mainly detoxified in peroxisomes by the enzyme CAT/catalase. As DEPP contains a peroxisomal-targeting-signal-type-2 (PTS2) sequence at its N-terminus that enables protein import into peroxisomes, we analyzed the effect of DEPP on peroxisomal function by measuring the catalase enzyme activity. Catalase activity was reduced by conditional DEPP overexpression and significantly increased in DEPP-knockdown cells. Using live cell imaging and fluorescent peroxisomal and mitochondrial probes we demonstrate that DEPP localizes to peroxisomes and mitochondria in neuroblastoma cells. The combined data indicate that DEPP reduces peroxisomal activity and thereby impairs the cellular ROS detoxification capacity and contributes to death sensitization.
Publication Title
C10ORF10/DEPP, a transcriptional target of FOXO3, regulates ROS-sensitivity in human neuroblastoma.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
We demonstrate that the catalytic subunit of Polycomb Repressive Complex 2, EZH2, is targeted by the MELK-FOXM1 complex, which in turn promotes resistance to radiation in GSCs. Clinically, EZH2 and MELK are co-expressed in GBM and significantly induced in post-irradiation recurrent tumors whose expression inversely correlated with patient prognosis. Through gain-and loss-of-function study, our data show that MELK or FOXM1 contributes on GSC radioresistance by regulation of EZH2.
Publication Title
EZH2 protects glioma stem cells from radiation-induced cell death in a MELK/FOXM1-dependent manner.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Increasing evidence suggests that cancer arises from cells that are capable of initiating and sustaining neoplastic tissue growth, termed cancer stem cells (CSCs). Of central scientific and clinical relevance, cells with CSC properties are enriched for chemo- and radiation resistance and therefore may represent a population of cells that must be therapeutically targeted to prevent cancer recurrence/relapse 1. Human CSCs were first isolated in neoplastic hematopoietic tissue that manifests leukemias such as adult acute myeloid leukemia (AML) 2. AML stem cells represent a benchmark model of human CSC biology, ultimately motivating foundational studies leading to the identification of CSCs from solid tumours such as breast and colon 3. Independent of tissue type, a consistent feature of CSCs is their uncontrolled self-renewal capacity and differentiation blockade that have been commonly related to aberrant activation of pro-oncogenic events such as dysregulation of CBP/p300 transcriptional regulation involving -catenin 4. However, the transcriptional networks involving CBP/p300/-catenin complex have been shown to be equally critical to maintain normal stem cell (SCs) self-renewal for tissue homeostasis and regeneration 5. Here, we identify Sam68 as a distinct target that affords the ability to uniquely regulate CBP mediated transcription in human CSCs. Using a small molecule that targets Sam68, we reveal that shifting its affinity for CBP disrupts CBP/-catenin complexes, leading to immediate changes in histone H3 (K14 and K18) acetylation. Chemical targeting of Sam68 induced global changes in transcriptional programs of patient AML cells involving apoptosis and differentiation and was able to uniquely reduce neoplastic self-renewal of human CSCs in an in vivo model of patient specific acute myeloid leukemia (AML). Our study establishes an approach whereby the CBP/-catenin transcriptome can be uniquely targeted via Sam68 based vulnerability of CSCs that impacts neoplastic differentiation and self-renewal.
Publication Title
Sam68 Allows Selective Targeting of Human Cancer Stem Cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples