Analysis of adult and childhood tumors reveals activation of an E2F3 signature unique to Wilms tumors.
The E2F3-Oncomir-1 axis is activated in Wilms' tumor.
Sex, Age
View SamplesDespite the frequent detection of circulating tumor antigen-specific T cells, either spontaneously or following active immunization or adoptive transfer, immune-mediated cancer regression occurs only in the minority of patients. One theoretical rate-limiting step is whether effector T cells successfully migrate into metastatic tumor sites. Affymetrix gene expression profiling performed on a series of metastatic melanoma biopsies revealed a major segregation of samples based on the presence or absence of T cell-associated transcripts. The presence of lymphocytes correlated with the expression of defined chemokine genes. A subset of 6 chemokines (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL10) was confirmed by protein array and/or quantitative RT-PCR to be preferentially expressed in tumors that contained T cells. Corresponding chemokine receptors were found to be upregulated on human CD8+ effector T cells, and transwell migration assays confirmed the ability of each of these chemokines to promote migration of CD8+ effector cells in vitro. Screening by chemokine protein array identified a subset of melanoma cell lines produced a similar broad array of chemokines. These melanoma cells more effectively recruited human CD8+ effector T cells when implanted as xenografts in NOD/scid mice in vivo. Chemokine blockade with specific antibodies inhibited migration of CD8+ T cells. Our results suggest that lack of critical chemokines in a subset of melanoma metastases may limit the migration of activated T cells, which in turn could limit the effectiveness of anti-tumor immunity.
Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment.
No sample metadata fields
View SamplesCeliac disease is an intestinal inflammatory disorder induced by dietary gluten in genetically susceptible individuals. The mechanisms underlying the massive expansion of interferon gproducing intraepithelial cytotoxic T lymphocytes (CTLs) and the destruction of the epithelial cells lining the small intestine of celiac patients have remained elusive. We report massive oligoclonal expansions of intraepithelial CTLs that exhibit a profound genetic reprogramming of natural killer (NK) functions. These CTLs aberrantly expressed cytolytic NK lineage receptors, such as NKG2C, NKp44, and NKp46, which associate with adaptor molecules bearing immunoreceptor tyrosine-based activation motifs and induce ZAP-70 phosphorylation, cytokine secretion, and proliferation independently of T cell receptor signaling. This NK transformation of CTLs may underlie both the self-perpetuating, gluten-independent tissue damage and the uncontrolled CTL expansion leading to malignant lymphomas in severe forms of celiac disease. Because similar changes were detected in a subset of CTLs from cytomegalovirus-seropositive patients, we suggest that a stepwise transformation of CTLs into NK-like cells may underlie immunopathology in various chronic infectious and inflammatory diseases.
Reprogramming of CTLs into natural killer-like cells in celiac disease.
No sample metadata fields
View SamplesWe generated primary cultures from renal cell carcinoma and matched normal primary kidney cortex tubule cell cultures from 3 patients. Early passage cultures of these two cell types were subjected to chromatin accessibility profiling (DNase-seq) and gene expression profiling (RNA-seq). Studying these paired and patient-matched controlled data sets will shed light on the epigenomic changes that underlie transformation of kidney tubules into malignant cancers. Overall design: Paired DNase-seq and RNA-seq data sets from 2 different primary human kidney cell types (normal and cancer) Note from submitter: The HIM23 samples have a more narrow consent and their raw data will be submitted to dbGaP.
Integrated epigenomic profiling reveals endogenous retrovirus reactivation in renal cell carcinoma.
Sex, Age, Cell line, Subject
View SamplesBACKGROUND: Despite the moderate incidence of papillary renal cell carcinoma
A molecular classification of papillary renal cell carcinoma.
No sample metadata fields
View SamplesSummary:
HCaRG increases renal cell migration by a TGF-alpha autocrine loop mechanism.
No sample metadata fields
View SamplesHEK293 cells were transfected with control plasmid (pcDNAI/Neo;Invitrogen) or with the plasmid encoding HCaRG. Stable transfectants were synchronized and grown in the presence of 10% FBS for 48 h. Total RNAs were purified with the mini RNeasy kit (Qiagen).
HCaRG increases renal cell migration by a TGF-alpha autocrine loop mechanism.
No sample metadata fields
View SamplesTo investigate the response of Arabidopsis thaliana plants to non-freezing, cool temperatures, we subjected four week old plants to various chilling temperatures at defined times during the diurnal cycle to control for diurnal effects on transcription. From the same plants, metabolites and enzyme activities were measured as well. Interestingly a gradual change could be observed over a wide range of temperatures. Some of which could be attributed to the CBF program.
Multilevel genomic analysis of the response of transcripts, enzyme activities and metabolites in Arabidopsis rosettes to a progressive decrease of temperature in the non-freezing range.
Specimen part
View SamplesThe SCL and LMO1 oncogenic transcription factors reprogram thymocytes into self-renewing pre-leukemic stem cells (pre-LSCs). Here we report that SCL directly interacts with LMO1 to activate the transcription of a self-renewal program coordinated by LYL1.
SCL, LMO1 and Notch1 reprogram thymocytes into self-renewing cells.
Age, Specimen part
View SamplesThe Drosophila TRIM-NHL protein Brain tumor (Brat) plays important roles during early embryogenesis, in cell fate decisions, during neurogenesis and in mature neurons. Brat is an RNA-binding protein and functions as translational repressor. However, which RNAs Brat regulates and how RNA-binding specificity is achieved, is unknown. Using RNA-Immunoprecipitation we identify Brat-bound mRNAs in Drosophila embryos and define a consensus binding motif.
The Crystal Structure of the NHL Domain in Complex with RNA Reveals the Molecular Basis of Drosophila Brain-Tumor-Mediated Gene Regulation.
Specimen part
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