The Affymetrix Human Genome U133 Plus 2.0 Array was used to examine the Genome wide transcriptional changes which follow the treatment of AML xenografts with either PBS control or combination of decitabine (DAC) and cytarabine (Ara-C). Animals were treated with PBS, DAC alone, Ara-C alone, DAC and Ara-C combined (D+A), DAC followed by Ara-C (D/A) or Ara-C followed by DAC (A/D).
Sequential treatment with cytarabine and decitabine has an increased anti-leukemia effect compared to cytarabine alone in xenograft models of childhood acute myeloid leukemia.
Specimen part, Disease
View SamplesEpstein-Barr virus (EBV) is an oncogenic virus that is associated with the pathogenesis of several human lymphoid malignancies, including Hodgkin's lymphoma. Infection of normal resting B cells with EBV results in activation to lymphoblasts that are phenotypically similar to those generated by physiological stimulation with CD40L plus IL-4. One important difference is that infection leads to the establishment of permanently growing lymphoblastoid cell lines, whereas CD40L/IL-4 blasts have finite proliferation life-spans. To identify early events which might later determine why EBV infected blasts go on to establish transformed cell lines, we performed global transcriptome analyses on resting B cells and on EBV and CD40L/IL-4 blasts after 7 days culture. As anticipated, there was considerable overlap in the transcriptomes of the two types of lymphoblasts when compared to the original resting B cells, reflecting common changes associated with lymphocyte activation and proliferation.
Induction of interferon-stimulated genes on the IL-4 response axis by Epstein-Barr virus infected human b cells; relevance to cellular transformation.
No sample metadata fields
View SamplesIn this study, we have investigated the effect of LMP2A on gene expression in normal human GC B cells using a non-viral vector based system
Suppression of the LMP2A target gene, EGR-1, protects Hodgkin's lymphoma cells from entry to the EBV lytic cycle.
Specimen part, Subject
View SamplesGene expression was compared between four B-cell derived HL cell lines (L428, L1236, L591, KMH2) and GC B cells from three different patients.
The Epstein-Barr virus oncoprotein, latent membrane protein-1, reprograms germinal centre B cells towards a Hodgkin's Reed-Sternberg-like phenotype.
No sample metadata fields
View SamplesIn this study, we have investigated the effect of BLIMP1 on gene expression, cell differentiation and pathogenesis in normal human GC B cells using a non-viral vector based system
Down-regulation of BLIMP1α by the EBV oncogene, LMP-1, disrupts the plasma cell differentiation program and prevents viral replication in B cells: implications for the pathogenesis of EBV-associated B-cell lymphomas.
Specimen part
View SamplesIn this study, we have investigated the effect of lysine-specific demethylase 6B (KDM6B) on gene expression in normal human germinal center (GC) B cells using a non-viral vector-based system.
The H3K27me3 demethylase, KDM6B, is induced by Epstein-Barr virus and over-expressed in Hodgkin's Lymphoma.
Specimen part
View SamplesIn this study, we have investigated the effect of LMP1 on gene expression in normal human GC B cells using a non-viral vector based system
The Epstein-Barr virus oncoprotein, latent membrane protein-1, reprograms germinal centre B cells towards a Hodgkin's Reed-Sternberg-like phenotype.
No sample metadata fields
View SamplesTissue-specific comparison of gene expression levels in T65H translocation mice, either with or without uniparental duplications of Chrs 7 & 11. Identification of highly differentially expressed transcripts.
Chromosome-wide identification of novel imprinted genes using microarrays and uniparental disomies.
Specimen part
View SamplesTo dissect the impact of nuclear and extranuclear mutant htt on the initiation and progression of disease, we generated a series of transgenic mouse lines in which nuclear localization (NLS) or nuclear export sequences (NES) have been placed N-terminal to the htt exon 1 protein carrying 144 glutamines. Our data indicate that the exon 1 mutant protein is present in the nucleus as part of an oligomeric or aggregation complex. Increasing the concentration of the mutant transprotein in the nucleus is sufficient for, and dramatically accelerates the onset and progression of behavioral phenotypes. Furthermore, nuclear exon 1 mutant protein is sufficient to induce cytoplasmic neurodegeneration and transcriptional dysregulation. However, our data suggests that cytoplasmic mutant exon 1 htt, if present, contributes to disease progression.
Contribution of nuclear and extranuclear polyQ to neurological phenotypes in mouse models of Huntington's disease.
No sample metadata fields
View SamplesHuntingtons disease (HD) is a neurodegenerative disorder that is associated with the deposition of proteinaceous aggregates in the brains of HD patients and mouse models. Previous studies have suggested that wide-scale disruption of protein homeostasis occurs in protein folding diseases. Protein homeostasis can be maintained by activation of the heat shock response (HSR) via the transcription factor heat shock factor 1 (HSF1), the pharmacological activation of which can be achieved by Hsp90 inhibition and has been demonstrated to be beneficial in cell and invertebrate models of HD. Whether the HSR is functional in HD and whether its activation has therapeutic potential in mammalian HD models is currently unknown. To address these issues, we used a novel, brain penetrant Hsp90 inhibitor to activate the HSR in brain after systemic administration. Microarrays, quantitative PCR and western blotting showed that the HSR becomes impaired with disease progression in two mouse models of HD and that this originates at the level of transcription.
Altered chromatin architecture underlies progressive impairment of the heat shock response in mouse models of Huntington disease.
Sex, Age, Specimen part, Treatment
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