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GSE13258
Caenorhabditis elegans
15 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
Expession data from L1-L2 stage nematodes (C. elegans), wild type and four mutants (alg-1, zfp-1, rde-4, lin-35).
Publication Title
RNA interference and retinoblastoma-related genes are required for repression of endogenous siRNA targets in Caenorhabditis elegans.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This Series represents the gene expression profiles of patients with multiple myeloma who have been treated previously. In brief, Total Therapy 6 (TT6) is an open label phase 2 protocol for patients with symptomatic multiple myeloma, who had been treated with more than one cycle of prior therapy excluding autologous hematopoietic stem cell transplant. This protocol was approved by the institutional review board on March 25, 2009 (IRB#108053). The TT6 treatment regimen consists of induction therapy with Melphalan/Bortezomib/Thalidomide/Dexamethasone/Cisplatin/Doxorubicin/Cyclophosphamide/Etoposide (M-VTD-PACE) followed by a high dose M-VTD-PACE based tandem transplant. Maintenance therapy consists of Bortezomib/Lenalidomide/Dexamethasone alternating with Borteomib/Melphalan/Dexamethasone every months for 3 years.
Publication Title
Five gene probes carry most of the discriminatory power of the 70-gene risk model in multiple myeloma.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
IlluminaHiSeq2000
Description
Ewing sarcomas are characterized by the presence of EWS/ETS fusion genes in the absence of other recurrent genetic alterations and mechanisms of tumor heterogeneity that contribute to disease progression remain unclear. Mutations in the Wnt/beta-catenin pathway are rare in Ewing sarcoma but the Wnt pathway modulator LGR5 is often highly expressed, suggesting a potential role for the axis in tumor pathogenesis. We evaluated beta-catenin and LGR5 expression in Ewing sarcoma cell lines and tumors and noted marked intra- and inter-tumor heterogeneity. Tumors with evidence of active Wnt/beta-catenin signaling were associated with increased incidence of tumor relapse and worse overall survival. Paradoxically, RNA sequencing revealed a marked antagonism of EWS/ETS transcriptional activity in Wnt/beta-catenin activated tumor cells. Consistent with this, Wnt/beta-catenin activated cells displayed a phenotype that was reminiscent of Ewing sarcoma cells with partial EWS/ETS loss of function. Specifically, activation of Wnt/beta-catenin induced alterations to the actin cytoskeleton, acquisition of a migratory phenotype and up regulation of EWS/ETS-repressed genes. Notably, activation of Wnt/beta-catenin signaling led to marked induction of tenascin C (TNC), an established promoter of cancer metastasis, and an EWS/ETS-repressed target gene. Loss of TNC function in Ewing sarcoma cells profoundly inhibited their migratory and metastatic potential. Our studies reveal that heterogeneous activation of Wnt/beta-catenin signaling in subpopulations of tumor cells contributes to phenotypic heterogeneity and disease progression in Ewing sarcoma. Significantly, this is mediated, at least in part, by inhibition of EWS/ETS fusion protein function that results in de-repression of metastasis-associated gene programs. Overall design: Differential gene expression in highly Wnt-responsive cells.
Publication Title
Activation of Wnt/β-Catenin in Ewing Sarcoma Cells Antagonizes EWS/ETS Function and Promotes Phenotypic Transition to More Metastatic Cell States.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 750 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mesenchymal stem cells (MSCs) are an essential component of the bone marrow (BM) microenvironment and have shown to support cancer evolution in multiple myeloma (MM). Despite the increasing evidence that MM MSCs differ from their healthy counterparts, little knowledge exists as to whether MSCs independently influence disease outcome. The aim of the present study was to determine the importance of MSCs in disease progression and outcome in MM.
Publication Title
The Pattern of Mesenchymal Stem Cell Expression Is an Independent Marker of Outcome in Multiple Myeloma.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 130 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Purpose: Because dexamethasone remains a key component of myeloma therapy, we wished to examine the correlation of baseline and relapse expression levels of the glucocorticoid receptor gene NR3C1 with other clinical features. Experimental Design: We investigated the clinical impact of gene expression profiling (GEP)derived expression levels of NR3C1 in 351 patients with GEP data available at baseline and in 130 with data available at relapse, among 668 subjects accrued to Total Therapy 2 (TT2).
Publication Title
Thalidomide in total therapy 2 overcomes inferior prognosis of myeloma with low expression of the glucocorticoid receptor gene NR3C1.
Sample Metadata Fields
Disease, Treatment
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Natural Killer cells (NK), a major constituent of innate immune system, have the ability to kill the transformed and infected cells without prior sensitization; can be put to immunotherapeutic use against various malignancies. NK cells discriminate between normal cells and transformed cells via a balance of inhibitory and activating signals induced by interactions between NK cell receptors and target cell ligands. Present study investigates whether expansion of NK cells could augment their anti-myeloma (MM) activity. For NK cell expansion, peripheral blood mononuclear cells from healthy donors and myeloma patients were co-cultured with irradiated K562 cells transfected with 4-1BBL and membrane-bound IL15 (K562-mb15-41BBL). A genome-wide profiling approach was performed to identify gene expression signature in expanded NK (ENK) cells and non-expanded NK cells isolated from healthy donors and myeloma patients. A specific set of genes involved in proliferation, migration, adhesion, cytotoxicity, and activation were up regulated post expansion, also confirmed by flow cytometry. Exp-NK cells killed both allogeneic and autologous primary MM cells more avidly than non-exp-NK cells in vitro. Multiple receptors, particularly NKG2D, natural cytotoxicity receptors, and DNAM-1 contributed to target lysis, via a perforin mediated mechanism. In summary, vigorous expansion and high anti-MM activity both in vitro and in vivo provide the rationale for testing exp-NK cells in a clinical trial for high risk MM.
Publication Title
Highly activated and expanded natural killer cells for multiple myeloma immunotherapy.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Although several markers have been associated with the characterization of regulatory T cells (Treg) and their function, no studies have investigated the dynamics of their phenotype during infection. Since the necessity of Treg to control immunopathology has been demonstrated, we used the chronic helminth infection model S. mansoni to address the impact on the Treg gene repertoire. Before gene expression profiling we first chose to study the localization and antigen-specific suppressive nature of classically defined Treg during infection. Presence of Foxp3+ cells were found especially in the periphery of granulomas and isolated CD4+CD25hiFoxp3+ Treg from infected mice blocked IFN-gamma and IL-10 cytokine secretion from infected CD4+CD25- effector T cells (Teff). Furthermore the gene expression patterns of Treg and Teff showed that in total 474 genes were significantly regulated during chronic schistosomiasis. Upon k-means clustering we identified genes exclusively regulated in all four populations including Foxp3, CD103, GITR, OX40 and CTLA-4: classical Treg markers. During infection however, several non-classical genes were up-regulated solely within the Treg population such as Slpi, Gzmb, Mt1, Fabp5, Nfil3, Socs2, Gpr177 and Klrg1. Using RT-PCR we confirmed aspects of the microarray data and in addition showed that the expression profile of Treg from S. mansoni-infected mice is simultaneously unique and comparative with Treg derived from other infections
Publication Title
Pronounced phenotype in activated regulatory T cells during a chronic helminth infection.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Messenger RNA levels in eukaryotes are balanced by two consecutive regulatory layers. Primary, transcriptional regulation at the level of chromatin and secondary, post-transcriptional regulation of the initial transcript in the cytoplasm. Each layer is individually studied in mechanistic detail, while integration of both processes is required to quantify the individual contribution to steady-state RNA levels. Here we show that chromatin features are sufficient to model transcription rate but with different sensitivities in dividing versus post mitotic cells. In both cases chromatin derived transcript levels explains over 80% of variance in measured RNA level enabling to separate transcription from different post-transcriptional processes. By further inclusion of measurements of mRNA half-life and micro RNA expression data we identify a low quantitative contribution of RNA decay by either micro RNA or general differential turnover to final mRNA levels. Together this establishes a chromatin based quantitative model for the contribution of transcriptional and posttranscriptional processes to steady-state levels of messenger RNA.
Publication Title
Chromatin measurements reveal contributions of synthesis and decay to steady-state mRNA levels.
Sample Metadata Fields
Specimen part, Disease, Treatment, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The JAK2 mutation V617F is detectable in a majority of patients with Ph-negative myeloproliferative neoplasms (MPN). Enforced expression of JAK2 V617F in mice induces myeloproliferation and bone marrow (BM) fibrosis suggesting a causal role for the JAK2 mutant in the pathogenesis of MPN. However, little is known about mechanisms and effector molecules contributing to JAK2 V617F-induced myeloproliferation and fibrosis. Here we show that JAK2 V617F promotes expression of oncostatin M (OSM) in neoplastic myeloid cells. Correspondingly, OSM was found to be overexpressed in the BM and elevated in the serum of patients with JAK2 V617F+ MPN. In addition, OSM secreted by JAK2 V617F+ cells stimulated growth of fibroblasts and microvascular endothelial cells and induced the production of angiogenic and profibrogenic cytokines (HGF, VEGF, and SDF-1) in BM fibroblasts. All effects of MPN cell-derived OSM were blocked by a neutralizing anti-OSM antibody, whereas the production of OSM in MPN cells was effectively suppressed by a pharmacologic JAK2 inhibitor or RNAi-mediated knockdown of JAK2. In summary, JAK2 V617F-mediated upregulation of OSM may contribute to fibrosis, neoangiogenesis, and the cytokine storm observed in JAK2 V617F+ MPN, suggesting that OSM could serve as a novel therapeutic target molecule in these neoplasms.
Publication Title
Identification of oncostatin M as a JAK2 V617F-dependent amplifier of cytokine production and bone marrow remodeling in myeloproliferative neoplasms.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The purpose of the dataset is to analyze expression of genes induced by KRAS and regulated by TBK1
Publication Title
Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1.
Sample Metadata Fields
Specimen part
View Samples