Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1079676 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28065467_1.fastq.gz | Fastqsanger.gz | |||
| SRR28065467_2.fastq.gz | Fastqsanger.gz | |||
| SRR28065468_1.fastq.gz | Fastqsanger.gz | |||
| SRR28065468_2.fastq.gz | Fastqsanger.gz | |||
| SRR28065469_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 48 |
Similar Datasets
Project description:Pancreatic cancer is characterized by heavy desmoplasia. Triptolide and its water-soluble pro-drug Minnelide are extremely efficient against pancreatic cancer in animal models. However, the effects of triptolide on pancreatic cancer stromal cells are largely unknown. The aim of this project is to indentify potential cellular functions that are affected by triptolide in pancreatic cancer associated fibroblasts.
2016-11-01 | GSE74490 | GEO
Project description:Analyses of mirna transcript levels following exposure to the drug triptolide in vitro and prodrug minnelide in xenograft pancreatic tumor mouse models. Response of pancreatic adenocarcinoma cell lines to minelide in vitro and exposure to its prodrug triptolide in SCID mouse tumors derived from the same cell lines.
2013-11-12 | E-GEOD-46188 | biostudies-arrayexpress
Project description:Analyses of mirna transcript levels following exposure to the drug triptolide in vitro and prodrug minnelide in xenograft pancreatic tumor mouse models.
2013-11-12 | GSE46188 | GEO
Project description:While international consensus and the 2021 WHO classification recognize multiple molecular medulloblastoma subgroups, these are difficult to identify in current clinical practice. As a result, biology driven risk stratification and therapy assignment for medulloblastoma constitutes a major challenge. Here, we report mass spectrometry analysis of clinical samples as a method for medulloblastoma subgroup discovery and identify MYC immunohistochemistry (IHC) as a clinically tractable method for improved risk stratification.
2025-03-06 | PXD051319 | Pride
Project description:While international consensus and the 2021 WHO classification recognize multiple molecular medulloblastoma subgroups, these are difficult to identify in current clinical practice. As a result, biology driven risk stratification and therapy assignment for medulloblastoma constitutes a major challenge. Here, we report mass spectrometry analysis of clinical samples as a method for medulloblastoma subgroup discovery and identify MYC immunohistochemistry (IHC) as a clinically tractable method for improved risk stratification.
2026-02-23 | PXD051235 | Pride
Project description:We and others have demonstrated that MYC-amplified medulloblastoma (MB) cells are susceptible towards treatment with class I histone deacetylase inhibitors (HDACi). However, single drug treatment with HDACi has shown limited clinical efficacy. We hypothesized that addition of a second compound acting synergistically with HDACi may enhance efficacy. Gene expression changes in HDACi entinostat-treated cells identified, the cell cycle protein PLK1 as a potential second target. Indeed, MYC-amplified tumor cells are highly sensitive towards treatment with ATP-competitive PLK1 inhibitors as monotherapy. Moreover, entinostat and PLK1i in combination act synergistically in MYC-driven MB, exerting cytotoxic effects at clinically relevant concentrations. The downstream effect of both drugs as monotherapy and in combination is exerted via MYC-related pathways, pointing out the potential of MYC amplification as a clinically feasible predictive biomarker for patient selection. While entinostat significantly extended survival of mice implanted with orthotopic MYC-amplified MB PDX, there was no evidence of the improvement of survival when treating the animals with combination. However, further screening of blood-brain barrier penetrating PLK1is is necessary to determine the true potential of the combination. We use microarry to interrogate the expression differences in vehicle, entinostat, volasertib or combination treated cells.
2023-05-15 | GSE220748 | GEO
Project description:MYC is a driver oncogene in many cancers. Inhibition of MYC promises high therapeutic potential, but specific MYC inhibitors remain unavailable for clinical use. Previous studies suggest that MYC amplified Medulloblastoma cells are vulnerable to HDAC inhibition. Using co-immunoprecipitation, mass spectrometry and ChIP-sequencing we show that HDAC2 is a cofactor of MYC in MYC amplified primary medulloblastoma and cell lines. The MYC-HDAC2 complex is bound to genes defining the MYC-dependent transcriptional profile. Class I HDAC inhibition leads to stabilization and reduced DNA binding of MYC protein inducing a down-regulation of MYC activated genes (MAGs) and up-regulation of MYC repressed genes (MRGs). MAGs and MRGs are characterized by opposing biological functions and distinct E-box distribution. We conclude that MYC and HDAC2 (class I) are localized in a complex in MYC amplified medulloblastoma and drive a MYC-specific transcriptional program, which is reversed by the class I HDAC inhibitor entinostat. Thus, the development of HDAC inhibitors for treatment of MYC amplified medulloblastoma should include HDAC2 in its profile in order to directly target MYC´s trans-activating and trans-repressing function.
2020-09-01 | GSE143376 | GEO
Project description:MYC is a driver oncogene in many cancers. Inhibition of MYC promises high therapeutic potential, but specific MYC inhibitors remain unavailable for clinical use. Previous studies suggest that MYC amplified Medulloblastoma cells are vulnerable to HDAC inhibition. Using co-immunoprecipitation, mass spectrometry and ChIP-sequencing we show that HDAC2 is a cofactor of MYC in MYC amplified primary medulloblastoma and cell lines. The MYC-HDAC2 complex is bound to genes defining the MYC-dependent transcriptional profile. Class I HDAC inhibition leads to stabilization and reduced DNA binding of MYC protein inducing a down-regulation of MYC activated genes (MAGs) and up-regulation of MYC repressed genes (MRGs). MAGs and MRGs are characterized by opposing biological functions and distinct E-box distribution. We conclude that MYC and HDAC2 (class I) are localized in a complex in MYC amplified medulloblastoma and drive a MYC-specific transcriptional program, which is reversed by the class I HDAC inhibitor entinostat. Thus, the development of HDAC inhibitors for treatment of MYC amplified medulloblastoma should include HDAC2 in its profile in order to directly target MYC´s trans-activating and trans-repressing function.
2020-09-01 | GSE143384 | GEO
Project description:MYC is a driver oncogene in many cancers. Inhibition of MYC promises high therapeutic potential, but specific MYC inhibitors remain unavailable for clinical use. Previous studies suggest that MYC amplified Medulloblastoma cells are vulnerable to HDAC inhibition. Using co-immunoprecipitation, mass spectrometry and ChIP-sequencing we show that HDAC2 is a cofactor of MYC in MYC amplified primary medulloblastoma and cell lines. The MYC-HDAC2 complex is bound to genes defining the MYC-dependent transcriptional profile. Class I HDAC inhibition leads to stabilization and reduced DNA binding of MYC protein inducing a down-regulation of MYC activated genes (MAGs) and up-regulation of MYC repressed genes (MRGs). MAGs and MRGs are characterized by opposing biological functions and distinct E-box distribution. We conclude that MYC and HDAC2 (class I) are localized in a complex in MYC amplified medulloblastoma and drive a MYC-specific transcriptional program, which is reversed by the class I HDAC inhibitor entinostat. Thus, the development of HDAC inhibitors for treatment of MYC amplified medulloblastoma should include HDAC2 in its profile in order to directly target MYC´s trans-activating and trans-repressing function.
2020-09-01 | GSE143379 | GEO
Project description:Aberrant oncogenic activation of MYC drives tumorigenesis in the most aggressive subset of medulloblastoma, the most common malignant brain tumor in childhood. Metastatic dissemination at diagnosis and at recurrence is commonly observed in MYC-driven medulloblastomas. Since these tumors display remarkable resistance to standard multimodal therapeutic approaches, epigenetic modulators commonly altered in these tumors are highly promising targets for novel therapeutic approaches. Here, we report on a cross-entity, high-throughput epigenetic drug screen to evaluate therapeutic vulnerabilities in the most common malignant primary brain tumors. Specifically, we performed a primary screen including 78 epigenetic inhibitors and a secondary screen including 20 histone deacetylase inhibitors (HDACi) to compare response profiles in atypical teratoid/rhabdoid tumor (AT/RT, n=11), medulloblastoma (n=14), and glioblastoma (n=14). This unbiased approach revealed preferential activity of HDACi in MYC-driven medulloblastoma. Importantly, the class I selective HDACi CI-994 showed significant cell viability reduction mediated by induction of apoptosis in MYC-driven medulloblastoma, with little to no activity in non-MYC-driven medulloblastoma, AT/RT, and glioblastoma in vitro. Notably, CI-994 displayed antitumoral effects at the primary site and the metastatic compartment in two orthotopic mouse models of MYC-driven medulloblastoma. Furthermore, synergistic drug screening and RNA sequencing revealed NFκB pathway induction as a mechanism of resistance to CI-994 treatment. Taken together, our findings identified MYC pathway activation as a predictive biomarker for epigenetic treatment intervention in high-risk medulloblastoma and provide a preclinical rationale for further exploration of CI-994 combined with NFκB pathway inhibitors in the treatment of MYC-driven medulloblastoma.
2019-12-13 | GSE123760 | GEO