Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA96971 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Gene expression analysis of T-ALL cell lines treated with gamma-secretase inhibitor
| PRJNA97007 | ENA
Project description:This randomized phase I/II clinical trial is studying the side effects and best dose of gamma-secretase/notch signalling pathway inhibitor RO4929097 when given together with vismodegib and to see how well they work in treating patients with advanced or metastatic sarcoma. Vismodegib may slow the growth of tumor cells. Gamma-secretase/notch signalling pathway inhibitor RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vismodegib together with gamma-secretase/notch signalling pathway inhibitor RO4929097 may be an effective treatment for sarcoma.
| 2091475 | ecrin-mdr-crc
Project description:Gamma-secretase inhibitor plus fludarabine in CLL
| PRJNA219743 | ENA
Project description:Next generation sequencing was used to identify Notch mutations in a large collection of diverse solid tumors. NOTCH1 and NOTCH2 rearrangements leading to constitutive receptor activation were confined to triple negative breast cancers (TNBC, 6 of 66 tumors). TNBC cell lines with NOTCH1 rearrangements associated with high levels of activated NOTCH1 (N1-ICD) were sensitive to the gamma-secretase inhibitor (GSI) MRK-003, both alone and in combination with pacitaxel, in vitro and in vivo, whereas cell lines with NOTCH2 rearrangements were resistant to GSI. Immunohistochemical staining of N1-ICD in TNBC xenografts correlated with responsiveness, and expression levels of the direct Notch target gene HES4 correlated with outcome in TNBC patients. Activating NOTCH1 point mutations were also identified in other solid tumors, including adenoid cystic carcinoma (ACC). Notably, ACC primary tumor xenografts with activating NOTCH1 mutations and high N1-ICD levels were sensitive to GSI, whereas N1-ICD low tumors without NOTCH1 mutations were resistant. Gene expression profiling for Notch-sensitive cancer cell lines using RNA-seq, each sample with triplicates
2014-08-14 | E-GEOD-59810 | biostudies-arrayexpress
Project description:The intramembrane protease gamma-secretase has broad physiological functions, but also contributes to Notch-dependent tumors and Alzheimer’s disease. To identify naturally short substrates and non-substrates of gamma-secretase, we used four human cell lines of different tissue origins, breast cancer MCF7 cells, cervix carcinoma HeLa cells, T cell leukemia Jurkat cells and lymphoma U937 macrophage-like cells. The cell lines were treated overnight with the established gamma-secretase inhibitor DAPT or DMSO as a control. The proteomes of membrane fractions were determined by nano-liquid chromatography-tandem mass spectrometry and label-free quantitative proteomics. TNFRSF12A, PTPRCAP and C16orf54 were identified as potential naturally short gamma-secretase substrates, whereas other proteins with a short ectodomain including ‘pituitary tumor-transforming gene 1-interacting protein’ (PTTG1IP) did not show an increased abundance upon DAPT treatment.
2024-05-24 | PXD045701 | Pride
Project description:Analysis of five Notch signaling-dependent human T-ALL cell lines (ALLSIL, DND41, HPBALL, KOPTK1, TALL-1) treated with gamma-secretase inhibitor (GSI) to block Notch signaling. Samples include parental cells, cells rescued by retroviral transduction with ICN (a GSI-independent form of activated Notch1), and cells retrovirally transduced with c-Myc (an important downstream target of Notch1). Results allow segregation of bona fide Notch targets from other genes affected by gamma-secretase inhibition as well as from targets downstream of c-Myc. Thirty samples were analyzed. Five human T-ALL cell lines (ALLSIL, DND41, HPBALL, KOPTK1, TALL-1) were treated with gamma-secretase inhibitor (1.0 micromolar compound E) vs. DMSO vehicle control for 12 hours. Each cell line was also retrovirally transduced with ICN or c-Myc, FACS sorted, and then treated with GSI vs. DMSO.
2011-07-31 | E-GEOD-29959 | biostudies-arrayexpress
Project description:Here we modeled T-ALL resistance to Notch inhibition, identifying M-bM-^@M-^XpersisterM-bM-^@M-^Y cells that readily expand in the presence of gamma secretase inhibitor (GSI) and the absence of Notch signaling. Rare persister cells are already present in naM-CM-/ve T-ALL populations, and the reversibility of the phenotype is suggestive of an epigenetic mechanism. Relative to GSI-sensitive cells, persisters activate distinct signaling and gene expression programs, and exhibit global chromatin compaction. A shRNA screen identified chromatin regulators whose depletion preferentially impairs persister cell viability, including BRD4, an acetyl-histone reader. BRD4 is up-regulated in the persisters and binds enhancers near genes with critical functions in T-ALL, including MYC and BCL2. Treatment of persisters with the BRD4 inhibitor JQ1 down-regulates these targets and induces growth arrest and apoptosis, at doses well tolerated by GSI-sensitive cells. Prompted by these findings, we examined and established the efficacy of GSI M-bM-^@M-^S JQ1 combination therapy against primary human leukemias in vivo. Our findings establish a role for epigenetic heterogeneity in leukemia drug resistance and suggest the potential of combination therapies that include epigenetic modulators to prevent and treat resistant disease. Examination of gene expression profiles in the T cell leukemia cell lines DND-41 and KOPT-K1 after chronic treatment with gamma Secretase inhibitor (Compound E, 1 uM, EMD4 Bioscience; persister) or vehicle (naM-CM-/ve). 2 replicates in each group.
2014-03-01 | E-GEOD-54378 | biostudies-arrayexpress
Project description:Here we modeled T-ALL resistance to Notch inhibition, identifying M-bM-^@M-^XpersisterM-bM-^@M-^Y cells that readily expand in the presence of gamma secretase inhibitor (GSI) and the absence of Notch signaling. Rare persister cells are already present in naM-CM-/ve T-ALL populations, and the reversibility of the phenotype is suggestive of an epigenetic mechanism. Relative to GSI-sensitive cells, persisters activate distinct signaling and gene expression programs, and exhibit global chromatin compaction. A shRNA screen identified chromatin regulators whose depletion preferentially impairs persister cell viability, including BRD4, an acetyl-histone reader. BRD4 is up-regulated in the persisters and binds enhancers near genes with critical functions in T-ALL, including MYC and BCL2. Treatment of persisters with the BRD4 inhibitor JQ1 down-regulates these targets and induces growth arrest and apoptosis, at doses well tolerated by GSI-sensitive cells. Prompted by these findings, we examined and established the efficacy of GSI M-bM-^@M-^S JQ1 combination therapy against primary human leukemias in vivo. Our findings establish a role for epigenetic heterogeneity in leukemia drug resistance and suggest the potential of combination therapies that include epigenetic modulators to prevent and treat resistant disease. Examination of 5 different histone modifications and BRD4 in the T cell leukemia cell lines DND-41 and KOPT-K1 after chronic treatment with gamma Secretase inhibitor (Compound E, 1 uM, EMD4 Bioscience; persister) or vehicle (naM-CM-/ve).
2014-03-01 | E-GEOD-54379 | biostudies-arrayexpress
Project description:To determine genes in FL HSCs that are sensitive to Notch signagling, E14.5 FL cells were cultured on DL1( to stimulate Notch signaling). Cells were cultured in the presence of DMSO (vehicle control) or gamma secretase inhibitor (1uM) for 4 hrs or 10hrs. Gamma secretase inhibitor was used to inhibit Notch signaling. SLAM-LSKs were sorted and used for RNA preparation.
2014-01-28 | GSE53713 | GEO
Project description:Expression data from 3 gamma-secretase or mock-treated mantle cell lymphoma (MCL) cell lines
| PRJNA150467 | ENA