Ontology highlight
ABSTRACT:
PROVIDER: PRJNA948704 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway activation contributes to mantle cell lymphoma (MCL) pathogenesis and drug resistance. However, the use of mTOR inhibitors as single agents have shown limited clinical efficacy in relation with drug activation of feedback loops. Selective PI3K inhibition or dual PI3K/mTOR catalytic inhibition are different therapeutic approaches developed to achieve effective pathway blockage. Here, we evaluated the antitumor activity of a mTOR inhibitor, a pan-PI3K inhibitor and a dual PI3K/mTOR inhibitor in primary MCL cells. We found that dual PI3K/mTOR inhibitor modulated angiogenesis, tumor invasiveness and cytokine signaling compared to a mTOR inhibitor and a pan-PI3K inhibitor in MCL. We used microarrays to compare the effect of these three compounds in MCL and identified distinct classes of down-regulated genes modulated by each compound. Global RNA expression in primary cells from two MCL patients treated with a mTOR inhibitor, a pan-PI3K inhibitor and a dual PI3K/mTOR inhibitor for 8 hours
2013-12-14 | E-GEOD-53309 | biostudies-arrayexpress
Project description:Phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway activation contributes to mantle cell lymphoma (MCL) pathogenesis and drug resistance. However, the use of mTOR inhibitors as single agents have shown limited clinical efficacy in relation with drug activation of feedback loops. Selective PI3K inhibition or dual PI3K/mTOR catalytic inhibition are different therapeutic approaches developed to achieve effective pathway blockage. Here, we evaluated the antitumor activity of a mTOR inhibitor, a pan-PI3K inhibitor and a dual PI3K/mTOR inhibitor in primary MCL cells. We found that dual PI3K/mTOR inhibitor modulated angiogenesis, tumor invasiveness and cytokine signaling compared to a mTOR inhibitor and a pan-PI3K inhibitor in MCL. We used microarrays to compare the effect of these three compounds in MCL and identified distinct classes of down-regulated genes modulated by each compound.
2013-12-14 | GSE53309 | GEO
Project description:Histone deacetylases (HDACs) regulate gene expression. Inhibition of class I HDACs has been shown to inhibit cancer cell growth. Largazole, a new potent HDAC inhibitor, shows strong antitumor activity, presumably by modulating transcription of cancer relevant genes. We used microarray analysis of human HCT116 colorectal carcinoma cell line to determine the gene expression profile after largazole treatment in comparison with other HDAC inhibitors (FK228 and SAHA). The goal was to identify regulated genes that can be linked to the antiproliferative effects of these HDAC inhibitors in HCT116 cells.
2010-08-28 | GSE22061 | GEO
Project description:Analysis of the effects of a dual specificity PI3K/mTOR inhibitor on two human ovarian cell lines, OV2008 and MCAS. Results provide insight into the adaptive response to PI3K/mTOR inhibition in matrix attached ovarian cancer cells. The PI3K/mTOR-pathway is the most commonly deregulated pathway in epithelial cancers and thus represents an important target for cancer therapeutics. Here we show that dual inhibition of PI3K/mTOR in ovarian cancer 3D-spheroids leads to death of the inner matrix-deprived cells, whereas matrix-attached cells are resistant. Resistance is associated with up-regulation of a cellular survival program that involves both FOXO-regulated transcription and a novel translational resistance mechanism resulting in specific up-regulation of IRES-mediated, cap-independent translation. Inhibition of any of several up-regulated proteins, including Bcl-2, EGFR, or IGF1R, abrogates resistance to dual PI3K/mTOR inhibition. These results demonstrate that acute adaptive response to PI3K/mTOR inhibition resembles well-conserved adaptive response to nutrient and growth factor deprivation and how development of rational drug combinations can bypass resistance mechanisms. Total RNA was isolated 6h and 24h after treatment with 1 M-NM-<M NVP-BEZ235 or DMSO vehicle control from 3D grown structures
2012-03-13 | E-GEOD-28992 | biostudies-arrayexpress
Project description:Targeting PI3K/mTOR signaling exerts potent antitumor activity in pheochromocytoma in vivo
| PRJNA325811 | ENA
Project description:Histone deacetylases (HDACs) regulate gene expression. Inhibition of class I HDACs has been shown to inhibit cancer cell growth. Largazole, a new potent HDAC inhibitor, shows strong antitumor activity, presumably by modulating transcription of cancer relevant genes. We used microarray analysis of human HCT116 colorectal carcinoma cell line to determine the gene expression profile after largazole treatment in comparison with other HDAC inhibitors (FK228 and SAHA). The goal was to identify regulated genes that can be linked to the antiproliferative effects of these HDAC inhibitors in HCT116 cells. To characterize the genes regulated by Largazole, SAHA and FK228, genome-wide gene expression analysis was carried out. Human HCT116 colorectal carcinoma cells (400,000) were seeded per well (6-well dish) and one day later treated with Largazole, SAHA, FK228 and vehicle control. 10 h later, total RNA was extracted and processed for hybridization to an Affymetrix Human Genome U133 2.0 GeneChip. Global alterations in transcript levels upon Largazole, SAHA and FK228 treatment were determined through comparison with data derived from cells treated with vehicle control. The experiment was carried out in duplicate.
2010-08-28 | E-GEOD-22061 | biostudies-arrayexpress
Project description:This study is an open label non randomized study of hydroxychloroquine (HCQ) with histone deacetylase (HDAC) inhibitor Vorinostat in patients with advanced solid tumors to determine the maximum tolerated dose (MTD) and to evaluate the safety and antitumor activity of this drug combination.
| 2081555 | ecrin-mdr-crc
Project description:Analysis of the effects of a dual specificity PI3K/mTOR inhibitor on two human ovarian cell lines, OV2008 and MCAS. Results provide insight into the adaptive response to PI3K/mTOR inhibition in matrix attached ovarian cancer cells. The PI3K/mTOR-pathway is the most commonly deregulated pathway in epithelial cancers and thus represents an important target for cancer therapeutics. Here we show that dual inhibition of PI3K/mTOR in ovarian cancer 3D-spheroids leads to death of the inner matrix-deprived cells, whereas matrix-attached cells are resistant. Resistance is associated with up-regulation of a cellular survival program that involves both FOXO-regulated transcription and a novel translational resistance mechanism resulting in specific up-regulation of IRES-mediated, cap-independent translation. Inhibition of any of several up-regulated proteins, including Bcl-2, EGFR, or IGF1R, abrogates resistance to dual PI3K/mTOR inhibition. These results demonstrate that acute adaptive response to PI3K/mTOR inhibition resembles well-conserved adaptive response to nutrient and growth factor deprivation and how development of rational drug combinations can bypass resistance mechanisms.
2012-03-13 | GSE28992 | GEO
Project description:CUDC-907 is a small-molecule dual-acting inhibitor of HDACs and PI3Ks, which effectively suppresses the growth and survival of MYC-altered DLBCL. To evaluate the effect of CUDC-907 on MYC-associated genes, two DLBCL cell lines were treated with CUDC-907, a total of 948 differentially regulated genes were identified. 24 genes from the CUDC-907–regulated 948-gene set present either in the "HALLMARK_MYC_TARGETS_V1” 200-gene set or in the “HALLMARK_MYC_TARGETS_V2” 58-gene set in the Molecular Signatures Database (MSigDB). We then computed the correlation coefficients (r) between gene expression levels and MYC protein levels across all samples in the TCGA DLBCL dataset. We found that mRNA expression changes induced by CUDC-907 in the two DLBCL cell lines are negatively correlated with correlation coefficients between expression levels and MYC protein level in the TCGA DLBCL dataset
2016-11-02 | GSE89339 | GEO