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SRP093784
Mus musculus
84 Downloadable Samples
Illumina HiSeq 2000
Description
It is well understood how proteins regulate cell fate, both in normal development and disease. However, a substantial fraction of the genome is transcribed in a cell type- specific manner, producing long non-coding RNAs (lncRNA) rather than protein- coding transcripts. Here we systematically characterize transcriptional dynamics (both mRNA and lncRNA) during hematopoiesis and in hematological malignancies. We present de novo assembled transcriptome models and expression values for hematopoietic lncRNAs. We found lncRNAs to be regulated during differentiation and misregulated in disease. We assessed lncRNA function via an in vivo RNAi screen in a model of acute myeloid leukemia. With this approach, we identified several lncRNAs essential for leukemia maintenance, and found that a number act by promoting leukemia stem cell signatures. Leukemia blasts show a myeloid differentiation phenotype when these lncRNAs were depleted, and our data indicates that this effect is mediated via effects on the c-MYC oncogene. Overall design: Transcriptome analysis was performed on cells expressing inducible shRNAs against the candidate lncRNAs. 9 different lncRNAs were knocked down with two different hairpins, in biological duplicates (clonar line A and B). Renilla lucifearase knockdown and Myc knocdown were also included as controls (3 biological replicates each).
Publication Title
lncRNA requirements for mouse acute myeloid leukemia and normal differentiation.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Previously we reported that a recombinant vaccinia virus (VACV) carrying a light-emitting fusion gene enters, replicates in, and reveals the locations of tumors in mice. A new recombinant VACV, GLV-1h68, as a simultaneous diagnostic and therapeutic agent, was constructed by inserting three expression cassettes (encoding Renilla luciferase-green fluorescent protein (RUC-GFP) fusion, b-galactosidase, and b-glucuronidase) into the F14.5L, J2R (encoding thymidine kinase, TK), and A56R (encoding hemagglutinin, HA) loci of the viral genome, respectively. Intravenous (i.v.) injections of GLV-1h68 (1 107 pfu/mouse) into nude mice with established (500 mm3) subcutaneous (s.c.) GI-101A human breast tumors were used to evaluate its toxicity, tumor targeting specificity and oncolytic efficacy. GLV-1h68 demonstrated an enhanced tumor targeting specificity and much reduced toxicity compared to its parental LIVP strains. The tumors colonized by GLV-1h68 exhibited growth, inhibition, and regression phases followed by tumor eradication within 130 days in 95% of the mice tested. Tumor regression in live animals was monitored in real time based on decreasing light emission, hence demonstrating the concept of a combined oncolytic virus-mediated tumor diagnosis and therapy system. Transcriptional profiling of regressing tumors based on a mouse-specific platform revealed gene expression signatures consistent with immune defense activation, inclusive of interferon stimulated genes (STAT-1 and IRF-7), cytokines, chemokines and innate immune effector function. These findings suggest that immune activation may combine with viral oncolysis to induce tumor eradication in this model, providing a novel perspective for the design of oncolytic viral therapies for human cancers.
Publication Title
Eradication of solid human breast tumors in nude mice with an intravenously injected light-emitting oncolytic vaccinia virus.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
LTB4, 50 nmol/L for 30 minutes, induced expression of 27 genes in cultured human elutriated monocytes comparred to vehicle (ethanol) treated control cells.
Publication Title
Cooperative and redundant signaling of leukotriene B4 and leukotriene D4 in human monocytes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 45 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene arrays were used to characterize the global transcriptional alterations in skin biopsy samples of EM lesions in comparison to controls. The transcriptional pattern in EM biopsies consisted of 254 differentially regulated genes (180 induced and 74 repressed) characterized by the induction of chemokines, cytokines, Toll-like receptors, antimicrobial peptides, monocytoid cell activation markers, and numerous genes annotated as interferon (IFN)-inducible. The IFN-inducible genes included 3 transcripts involved in tryptophan catabolism (IDO1, KMO, KYNU) that play a pivotal role in immune evasion by certain other microbial pathogens by driving the differentiation of regulatory T cells.
Publication Title
Transcriptome Assessment of Erythema Migrans Skin Lesions in Patients With Early Lyme Disease Reveals Predominant Interferon Signaling.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Cdk4/6 inhibitors have shown to increase overall survival in hormone-positive breast tumors, but whether other solid tumors could respond to these inhibitors has not yet defined. Here we show that Palbociclib (a Cdk4/6 specific inhibitor in clinic use) treatment exerts antiproliferative effects in vivo using a bladder cancer cell lines.
Publication Title
CDK4/6 Inhibitor as a Novel Therapeutic Approach for Advanced Bladder Cancer Independently of <i>RB1</i> Status.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To elucidate effects of tumor host interactions in vivo in CLL, purified tumor cells were obtained concurrently from blood, bone marrow and/or lymph node and analyzed by gene expression profiling.
Publication Title
The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Melphalan-induced modulation of miR-221/222 levels in MM cells. Melphalan-resistant U266/LR7 cells showed the highest induction of miR-221/222 after drug exposure. To study the transcriptome perturbation induced in MM cells following the combination of miR-221/222 inhibitors plus melphalan we used the whole gene expression data
Publication Title
A 13 mer LNA-i-miR-221 Inhibitor Restores Drug Sensitivity in Melphalan-Refractory Multiple Myeloma Cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st), Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp)
Description
In this study we addressed subclonal evolutionary process after treatment and subsequent relapse in multiple myeloma (MM) in a cohort of 24 MM patients treated either with conventional chemotherapy or with the proteasome inhibitor, bortezomib. Because MM is a highly heterogeneous disease coupled with a large number of DNA copy number alterations (CNAs) and loss of heterozygosity (LOH), we focused our study on the secondary genetic events: 1q21 gain, NF-kB activating mutations, RB1 and TP53 deletions, that seem to reflect progression. By using genome-wide high resolution SNP arrays we identified subclones with nonlinear complex evolutionary histories in a third of patients with myeloma, the relapse clone apparently derived from a minor subclone at diagnosis. Such reordering of the spectrum of genetic lesions during therapy is likely to reflect selection of genetically distinct subclones not initially competitive against the dominant population that survived chemotherapy, thrived and acquired new anomalies. In addition we found that emergence of minor subclones at relapse was significantly associated with bortezomib treatment. Altogether, these data support the idea of new strategy of future clinical trials in MM that would combine targeted therapy and subpopulations control to eradicate all myeloma subclones in order to obtain long-term remission.
Publication Title
Minor clone provides a reservoir for relapse in multiple myeloma.
Sample Metadata Fields
Specimen part, Disease, Cell line, Subject
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Series GSE25262 patients on expression side.
Publication Title
Minor clone provides a reservoir for relapse in multiple myeloma.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Dysregulated oncogenic serine/threonine kinases play a pathological role in diverse forms of malignancies, including multiple myeloma (MM), and thus represent potential therapeutic targets. Here, we evaluated the biological and functional role of p21-activated kinase 4 (PAK4), and its potential as a new target in MM for clinical applications. PAK4 promoted MM cell growth and survival via activation of MM survival signaling pathways, including the MEK-ERK pathway. Furthermore, treatment with orally bioavailable PAK4 allosteric modulator (KPT-9274) significantly impacted MM cell growth and survival in a large panel of MM cell lines and primary MM cells alone and in the presence of bone marrow microenvironment. Intriguingly, we have identified FGFR3 as a novel binding partner of PAK4 and observed significant activity of KPT-9274 against t(4;14)-positive MM cells. These data support PAK4 as an oncogene in myeloma, and provide the rationale for the clinical evaluation of PAK4 modulator in myeloma.
Publication Title
Functional role and therapeutic targeting of p21-activated kinase 4 in multiple myeloma.
Sample Metadata Fields
Specimen part, Cell line
View Samples