Patient-derived HK-374 glioblastoma cells treated with radiation and ONC201
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA644645 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12169022_1.fastq.gz | Fastqsanger.gz | |||
| SRR12169022_2.fastq.gz | Fastqsanger.gz | |||
| SRR12169023_1.fastq.gz | Fastqsanger.gz | |||
| SRR12169023_2.fastq.gz | Fastqsanger.gz | |||
| SRR12169024_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:RNASeq results for HK-374 treated with DMSO, radiation, ONC201 or radiation plus ONC201
2020-07-08 | GSE153982 | GEO
Project description:Design and Biological Activity of a Novel Urea Compound Against Glioblastoma [HK-374]
| PRJNA1251661 | ENA
Project description:Despite advances in surgery and radiotherapy, glioblastoma (GBM) remains the deadliest adult brain cancer with unacceptable low median survival rates. Targeted therapies and biologics have failed to improve outcome and the standard-of-care against GBM has not changed in two decades. GBM, like many solid tumors are thought to be organized hierarchically with a small number of radiation- and chemotherapy-resistant glioma stem cells (GSCs) producing more differentiated progeny and can repopulate tumors after sublethal treatment.In this study we sought to develop novel compounds that cross the blood-brain barrier (BBB), target existing GSCs and interfere with glioma cell plasticity to prevent the induction of GSCs in response to irradiation. We show that novel urea compounds target existing GSCs, prevent the radiation-induced conversion of non-stem glioma cells into GSCs and prolong the median survival in mouse models of GBM with minimal normal tissue toxicity.
2025-04-17 | GSE294831 | GEO
Project description:The small molecule ONC201 is toxic in vitro to multiple cell lines and primary tumor samples of mantle cell lymphoma (MCL) and acute myeloid leukemia, even ones with unfavorable genetic features (notably including TP53 inactivation) or acquired resistance to other agents. Because the mechanism of action in these malignant hematologic cells appeared to differ from that in solid tumors, we performed gene expression profiling (GEP) studies on MCL lines treated with ONC201 and other agents with known mechanisms of action. Treatment of JeKo-1 cells with 5 uM ONC201 showed consistent and progressive increases or decreases over time in two sets of genes: upregulated genes, which implicated an ER stress response and mTOR pathway inhibition, and downregulated genes, which implicated reduced proliferation. These implicated effects of ONC201 were validated by confirmatory experiments. Similar GEP changes were observed in ONC201-naive Z138 cells after 24 hr of ONC201 treatment, but were not seen in Z138 cells made ONC201-resistant by chronic exposure. Finally, the GEP effects of ONC201 in JeKo-1 cells were mimicked by the ER stress inducer tunicamycin, but not by the direct MTOR inhibition rapamycin, further confirming an ER stress response and suggesting that inhibition of the mTOR pathway was by an indirect mechanism. For each experiment, cells from a single stock culture of each cell line used were aliquoted into individual culture plate wells, establishing individual replicates, and drugs were added to start the experiment. Treated replicates were harvested after the times of treatment indicated, by pelleting cells, lysing pellets in TriZOL, and freezing TriZOL until RNA isolation. Untreated replicates, serving as controls, were either harvested at the beginning of the experiment or at later times, as specified below.
2016-02-20 | E-GEOD-68091 | biostudies-arrayexpress
Project description:Two experiments were performed with ONC201/TIC10 in human colon cancer cell lines. The first experiment is TIC10-induced transcriptional changes at 48hrs in HCT116 p53-null cells (10uM). The second experiment is RKO cells, with and without acquired resistance to ONC201, treated with with ONC201 (10uM) for 48 hrs. For the first experiment, six samples of HCT116 p53-null cells with TIC10 (10uM) or DMSO treatment. Three replicates each. For the second experiment, six samples of wild-type RKO cells with ONC201 (10uM) or DMSO treatment and the same treatments for RKO cells with acquired resistance to ONC201.
2016-06-01 | E-GEOD-72865 | biostudies-arrayexpress
Project description:The small molecule ONC201 is toxic in vitro to multiple cell lines and primary tumor samples of mantle cell lymphoma (MCL) and acute myeloid leukemia, even ones with unfavorable genetic features (notably including TP53 inactivation) or acquired resistance to other agents. Because the mechanism of action in these malignant hematologic cells appeared to differ from that in solid tumors, we performed gene expression profiling (GEP) studies on MCL lines treated with ONC201 and other agents with known mechanisms of action. Treatment of JeKo-1 cells with 5 uM ONC201 showed consistent and progressive increases or decreases over time in two sets of genes: upregulated genes, which implicated an ER stress response and mTOR pathway inhibition, and downregulated genes, which implicated reduced proliferation. These implicated effects of ONC201 were validated by confirmatory experiments. Similar GEP changes were observed in ONC201-naive Z138 cells after 24 hr of ONC201 treatment, but were not seen in Z138 cells made ONC201-resistant by chronic exposure. Finally, the GEP effects of ONC201 in JeKo-1 cells were mimicked by the ER stress inducer tunicamycin, but not by the direct MTOR inhibition rapamycin, further confirming an ER stress response and suggesting that inhibition of the mTOR pathway was by an indirect mechanism.
2016-02-20 | GSE68091 | GEO
Project description:Glioblastoma is the deadliest brain tumor in adults and the standard-of-care consists of surgery followed by radiation and treatment with temozolomide. Overall survival times for patients suffering from glioblastoma are unacceptably low indicating an unmet need for novel treatment options. Using patient-derived glioblastoma lines and mouse models of glioblastoma we tested the effect of radiation and the dopamine receptor antagonist on glioblastoma self-renewal in vitro and survival in vivo. A possible resistance mechanism was investigated using RNA-Sequencing. Treatment of glioma cells with the dopamine receptor antagonist quetiapine reduced glioma cell self-renewal in vitro and combined treatment of mice with quetiapine and radiation prolonged the survival of glioma-bearing animals. The combined treatment induced the expression of genes involved in cholesterol biosynthesis. This rendered the tumors vulnerable to simultaneous treatment with atorvastatin and further significantly prolonged the survival of the animals. Our results indicate promising therapeutic efficacy with the triple combination of quetiapine, atorvastatin and radiation treatment against glioblastoma without increasing the toxicity of radiation. With both drugs readily available for clinical use our study could be rapidly translated into a clinical trial.
2021-01-28 | GSE165624 | GEO
Project description:We found that radiation treatment enhanced the expression of H3K27me3 in glioblastoma. Thus, we asked whether radiation contributed to the increase of global genomic H3K27me3 occupancy in glioblastoma. The Chip-seq results in GL261 cells showed that irradiation led to the increase of H3K27me3 occupancy ±50kb within the transcription start sites (TSS), especially the promoter sites (peaks±2kb within TSS). Some pathways, in which H3K27me3 peaks significantly enriched, were found. Chip-seq was conducted for H3K27me3 in glioblastoma cell line GL261 when GL261 cells were treated with or without irradiation.
2022-06-01 | GSE205062 | GEO
Project description:RNA-Seq analysis of prostate cancer cells primed to irradiation for 24hours with ONC201 shows a sustained suppression of transcripts encoding cell cycle regulators as well as components of the DNA damage response pathways.
2021-02-21 | GSE136975 | GEO
Project description:Brevundimonas sp. 374 Genome sequencing
| PRJNA182414 | ENA