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GSE78234
Homo sapiens
28 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We demonstrate the in vivo efficacy of the histone deacetylase inhibitor Panobinostat (LHB589) against MLL-rearranged ALL using xenograft mouse models of MLL-rearranged ALL cell lines and primary patient cells. Panobinostat monotherapy showed strong anti-leukaemic effects, extending survival and reducing overall disease burden. Comprehensive molecular analyses in vitro showed the anti-leukaemic activity in MLL-rearranged ALL to involve depletion of H2B ubiquitination via suppression of the RNF20/RNF40/WAC E3 ligase complex.
Publication Title
The HDAC inhibitor panobinostat (LBH589) exerts in vivo anti-leukaemic activity against MLL-rearranged acute lymphoblastic leukaemia and involves the RNF20/RNF40/WAC-H2B ubiquitination axis.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We investigated the anti-leukemic effects of the Bromodomain and Extra Terminal inhibitor I-BET151 on primary MLL-AF4 patient samples, using a xenotransplantation mouse model of MLL+ infant ALL in vivo. We reported that I-BET151 treatment impairs the engraftment and the disease burden of primary MLL+ infant ALL samples transplanted into immunedeficient mice. I-BET151 is able to arrest the growth of leukemic cells by blocking cell division and rapidly inducing apoptosis, through the deregulation of crucial target genes of the BRD4 and HOXA9/HOXA7 network. Moreover I-BET151 sensitizes glucocorticoid-resistant MLL+ cells to Prednisolone. Finally we observed that I-BET151 treatment is even more efficient when used in combination with HDAC inhibitor.
Publication Title
Antileukemic Efficacy of BET Inhibitor in a Preclinical Mouse Model of MLL-AF4<sup>+</sup> Infant ALL.
Sample Metadata Fields
Treatment, Subject
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Polycomb repressive complex 2-dependent and -independent functions of Jarid2 in transcriptional regulation in Drosophila.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Jarid2 was recently identified as an important component of the mammalian Polycomb Repressive Complex 2 (PRC2), where it has a major effect on PRC2 recruitment in mouse embryonic stem cells. Although Jarid2 is conserved in Drosophila, it has not previously been implicated in Polycomb (Pc) regulation. Therefore, we purified Drosophila Jarid2 and its associated proteins and find that Jarid2 associates with all of the known canonical PRC2 components, demonstrating a conserved physical interaction with PRC2 in flies and mammals. Furthermore, in vivo studies with Jarid2 mutants in flies demonstrate that among several histone modifications tested, only H3K27 methylation, the mark implemented by PRC2, was affected. Genome-wide profiling of Jarid2, Su(z)12 and H3K27me3 occupancy by ChIP-seq indicates that Jarid2 and Su(z)12 have a very similar distribution pattern on chromatin. However, Jarid2 and Su(z)12 occupancy levels at some genes are significantly different with Jarid2 being present at relatively low levels at many Pc response elements (PREs) of certain Homeobox (Hox) genes, providing a rationale for why Jarid2 was never identified in Pc screens. Gene expression analyses show that Jarid2 and E(z) (a canonical PRC2 component) are required not only for transcriptional repression but might also function in active transcription. Identification of Jarid2 as a conserved PRC2 interactor in flies provides an opportunity to begin to probe some of its novel functions in Drosophila development.
Publication Title
Polycomb repressive complex 2-dependent and -independent functions of Jarid2 in transcriptional regulation in Drosophila.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Cyanide is stoichiometrically produced as a co-product of the ethylene biosynthesis pathway, and it is detoxified by the b-cyanoalanine synthase enzyme. The molecular and phenotypical analysis of T-DNA insertional mutants of the mitochondrial b-cyanoalanine synthase CYS-C1 suggests that discrete accumulation of cyanide is not toxic for the plant and does not alter mitochondrial respiration rates, but does act as a strong inhibitor of root hair development. The cys-c1 null allele is defective in root hair formation and accumulates cyanide in root tissues. The root hair defect is phenocopied in wild type plants by the exogenous addition of cyanide to the growth medium and is reversed by the addition of hydroxocobalamin. Hydroxocobalamin not only recovers the root phenotype of the mutant, but also the formation of ROS at the initial step of the root hair tip. Transcriptional profile analysis of the cys-c1 mutant reveals that cyanide accumulation acts as a repressor signal for several genes encoding enzymes involved in cell wall rebuilding and the formation of the root hair tip, as well as genes involved in ethylene signaling and metabolism. Our results demonstrate that mitochondrial b-cyanoalanine synthase activity is essential to maintain a low level of cyanide for proper root hair development.
Publication Title
Mitochondrial beta-cyanoalanine synthase is essential for root hair formation in Arabidopsis thaliana.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 30 Downloadable Samples
Affymetrix Mouse Gene 2.1 ST Array (mogene21st), Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cinacalcet inhibits neuroblastoma tumor growth and upregulates cancer-testis antigens.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
CaSR modulation inhibits neuroblastoma growth
Publication Title
Cinacalcet inhibits neuroblastoma tumor growth and upregulates cancer-testis antigens.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st), Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
CaSR modulation inhibits neuroblastoma growth
Publication Title
Cinacalcet inhibits neuroblastoma tumor growth and upregulates cancer-testis antigens.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 222 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The tyrosine kinase ErbB2 positive breast tumors have more aggressive tumor growth, poorer clinical outcome, and more resistance to radiotherapy, chemotherapy and hormone therapy. A humanized anti-ErbB2 monoclonal antibody Herceptin and a small molecules inhibitor Lapatinib were developed and approved by FDA to treat patients with ErbB2 amplification and overexpression. Unfortunately, most ErbB2+ breast cancers do not respond to Herceptin and Lapatinib, and the majority of responders become resistant within 12 months of initial therapy (defined as secondary drug resistance). Such differences in response to Lapatinib treatment is contributed by substantial heterogeneity within ErbB2+ breast cancers. To address this possibility, we carried out transcriptomic analysis of mammary tumors from genetically diverse MMTV-ErbB2 mice. This will help us to have a better understanding of the heterogeneous response to ErbB2 targeted therapy and permit us to design better and more individualized (personalized) treatment strategies for human ErbB2 positive breast cancer.
Publication Title
Unraveling heterogeneous susceptibility and the evolution of breast cancer using a systems biology approach.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We describe a new mutant allele of the ACTIN2 gene with enhanced actin dynamics, displaying a broad array of twisting and bending phenotypes that resemble BR-treated plants. Moreover, auxin transcriptional regulation is enhanced on the mutant background, supporting the idea that shaping actin filaments is sufficient to modulate BR-mediated auxin responsiveness. The actin cytoskeleton thus functions as a scaffold for integration of auxin and BR signaling pathways.
Publication Title
Role of actin cytoskeleton in brassinosteroid signaling and in its integration with the auxin response in plants.
Sample Metadata Fields
No sample metadata fields
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