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GSE79316
Homo sapiens
12 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The PI3K/mammalian target of rapamycin (mTOR) pathway is dysregulated in over 50% of human GBM but remains a challenging clinical target. Inhibitors against PI3K/mTOR mediators have limited clinical efficacy as single agents. Gene expression profiling after PI3K/mTOR inhibition treatment was analyzed by Affymetrix microarrays.
Publication Title
MSK1-Mediated β-Catenin Phosphorylation Confers Resistance to PI3K/mTOR Inhibitors in Glioblastoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 83 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
PI3K inhibition synergizes with glucocorticoids but antagonizes with methotrexate in T-cell acute lymphoblastic leukemia.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line
View Samples- Homo sapiens
- 43 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The PI3K pathway is frequently hyperactivated in primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients harboring mutations in the PI3K negative regulator PTEN may be at increased risk of induction failure and relapse. In this study, we identified Myc as an important downstream integrator of PI3K pathway activity in T-ALL and we provide data supportive of an association of higher PI3K activity with glucocorticoid resistance and worse clinical outcome. The PI3K inhibitor AS605240 showed anti-leukemic activity and strong synergism with glucocorticoids both in vitro and in a NOD/SCID xenograft model of T-ALL. In contrast, PI3K inhibition showed antagonism with methotrexate and daunorubicin, drugs that preferentially target dividing cells. This antagonistic interaction, however, could be circumvented by the use of correct drug scheduling schemes. Our data indicate the potential benefits and difficulties for the incorporation of PI3K inhibitors in T-ALL therapy.
Publication Title
PI3K inhibition synergizes with glucocorticoids but antagonizes with methotrexate in T-cell acute lymphoblastic leukemia.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The PI3K pathway is frequently hyperactivated in primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients harboring mutations in the PI3K negative regulator PTEN may be at increased risk of induction failure and relapse. In this study, we identified Myc as an important downstream integrator of PI3K pathway activity in T-ALL and we provide data supportive of an association of higher PI3K activity with glucocorticoid resistance and worse clinical outcome. The PI3K inhibitor AS605240 showed anti-leukemic activity and strong synergism with glucocorticoids both in vitro and in a NOD/SCID xenograft model of T-ALL. In contrast, PI3K inhibition showed antagonism with methotrexate and daunorubicin, drugs that preferentially target dividing cells. This antagonistic interaction, however, could be circumvented by the use of correct drug scheduling schemes. Our data indicate the potential benefits and difficulties for the incorporation of PI3K inhibitors in T-ALL therapy.
Publication Title
PI3K inhibition synergizes with glucocorticoids but antagonizes with methotrexate in T-cell acute lymphoblastic leukemia.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Metastatic relapse is the major cause of death in neuroblastoma (NB), yet there are no therapies to specifically target metastases. To understand the molecular mechanisms mediating NB metastasis, we developed a mouse model using intracardiac injection and in vivo selection to isolate metastatic subpopulations that exhibited a higher propensity for bone and central nervous system metastases. Gene expression profiling revealed two distinct subtypes, primary and metastatic, with differential regulation of 412 genes and multiple pathways including CADM1, SPHK1, and YAP/TAZ whose expression independently predicted survival. Loss- and gain-of-function experiments with these genes demonstrated a rescue of metastatic phenotypes in multiple NB cell lines in vitro or in vivo. Treatment with the compounds SKI II and Verteporfin that target SPHK1 and YAP/TAZ, respectively, inhibited NB metastasis in vivo. In addition, using gene expression profiling from the metastatic subpopulations, a gene signature (MET-75) was identified that predicts NB survival of patients with metastatic disease. This model therefore identifies genes regulating metastasis and candidate therapeutics for metastatic NB
Publication Title
A Metastatic Mouse Model Identifies Genes That Regulate Neuroblastoma Metastasis.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The PI3K pathway is frequently hyperactivated in primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients harboring mutations in the PI3K negative regulator PTEN may be at increased risk of induction failure and relapse. In this study, we identified Myc as an important downstream integrator of PI3K pathway activity in T-ALL and we provide data supportive of an association of higher PI3K activity with glucocorticoid resistance and worse clinical outcome. The PI3K inhibitor AS605240 showed anti-leukemic activity and strong synergism with glucocorticoids both in vitro and in a NOD/SCID xenograft model of T-ALL. In contrast, PI3K inhibition showed antagonism with methotrexate and daunorubicin, drugs that preferentially target dividing cells. This antagonistic interaction, however, could be circumvented by the use of correct drug scheduling schemes. Our data indicate the potential benefits and difficulties for the incorporation of PI3K inhibitors in T-ALL therapy.
Publication Title
PI3K inhibition synergizes with glucocorticoids but antagonizes with methotrexate in T-cell acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 557 Downloadable Samples
Illumina HiSeq 2000
Description
The extent of transcriptional diversity in mouse NPCs is likely to be influenced by a variety of unexamined factors that include programmed cell death, genomic mosaicism as well as a variety of “environmental” influences such as changes in exposure to signaling lipids. We therefore used scRNA-seq to assess a cohort of cortical NPCs from an embryonic mouse. We demonstrate that PAGODA (Pathway And Geneset OverDispersion Analysis) effectively recovers the known neuroanatomical and functional organization of NPCs, identifying multiple aspects of transcriptional heterogeneity within the developing mouse cortex that are difficult to discern by the existing heterogeneity analysis approaches. Overall design: Examination of mouse NPC transcriptional heterogeneity via single cell RNA-seq
Publication Title
Characterizing transcriptional heterogeneity through pathway and gene set overdispersion analysis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 45 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression was measured on the Affymetrix platform in primary xenografts, xenograft-derived cell lines, secondary xenografts, normal lung, and primary tumors obtained from chemotherapy naive Small Cell Lung Cancer (SCLC). The SCLC primary xenografts were serially propagated in vivo in immunodeficient mice. Cell lines were derived from each xenograft and grown for 6 months using conventional tissue culture conditions. Secondary xenografts were obtained from cell cultures by re-implantation in immunodeficient mice. Such SCLC laboratory models were analyzed along with conventional SCLC cell lines and the derivative secondary xenografts, with normal lung and primary tumors, to assess irreversible gene expression changes induced by culturing conditions.
Publication Title
A primary xenograft model of small-cell lung cancer reveals irreversible changes in gene expression imposed by culture in vitro.
Sample Metadata Fields
Disease, Disease stage, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
In our efforts to evaluate the function of the IL-8 receptor CXCR2 in Acute Lymphoblastic Leukemia (ALL) cells, we made use of SB225002 (N-(2-hydroxy-4-nitrophenyl)-N-(2-bromophenyl)urea), a drug initially described as a CXCR2 antagonist. Although the CXCR2 receptor was found to be non-functional in ALL, B- and T-ALL cell lines were sensitive to SB225002.
Publication Title
SB225002 Induces Cell Death and Cell Cycle Arrest in Acute Lymphoblastic Leukemia Cells through the Activation of GLIPR1.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The molecular mechanism defining susceptibility of normal cells to oncogenic transformation may be a valuable therapeutic target. We characterized the cell of origin and its critical pathways in MN1 leukemias. Common myeloid (CMP), but not granulocyte-macrophage progenitors (CMP) could be transformed by constitutively overexpressed MN1. Complementation studies of CMP-signature genes in GMPs demonstrated that leukemogenicity of MN1 required the MEIS1/abdB-like HOX protein complex. Colocalization studies by ChIP-seq identified common chromatin targets of MN1 and MEIS1 that were associated with open chromatin and transcriptional activation. Transcriptional repression of MEIS1 target sites in established MN1 leukemias had antileukemic activity. As MN1 relies on but can not activate expression of MEIS1/abdB-like HOX proteins, transcriptional activity of these genes determines which cell is the cell of origin in MN1 leukemia.
Publication Title
Cell of origin in AML: susceptibility to MN1-induced transformation is regulated by the MEIS1/AbdB-like HOX protein complex.
Sample Metadata Fields
Specimen part
View Samples