Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Design and Biological Activity of a Novel Urea Compound Against Glioblastoma [HK-390_scRNA-seq]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE295096 | GEO | 2025/04/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	GSE295096_RAW.tar	Raw
	filelist.txt	Txt

Items per page:

1 - 3 of 3

Similar Datasets

Design and Biological Activity of a Novel Urea Compound Against Glioblastoma [HK-374]

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

Design and Biological Activity of a Novel Urea Compound Against Glioblastoma [HK-217_scRNAseq_MXC-017_in_vitro]

2025-04-22 | GSE294961 | GEO

Design and Biological Activity of a Novel Urea Compound Against Glioblastoma [scRNAseq_MXC-017_374_in_vivo]

2025-04-23 | GSE295066 | GEO

Design and Biological Activity of a Novel Urea Compound Against Glioblastoma [HK-244_scRNAseq_MXC-017_in_vitro]

2025-04-17 | GSE294815 | GEO

Design and Biological Activity of a Novel Urea Compound Against Glioblastoma [HK-374_bulkRNA-seq]

2025-04-26 | GSE295095 | GEO

A Proneural to Mesenchymal Transition Mediated by NFkB Promotes Radiation Resistance in Glioblastoma (part 1)

Project description:SUMMARY Despite numerous genome-wide association studies involving glioblastoma (GBM), few therapeutic targets have been identified for this disease. Using patient derived glioma sphere cultures (GSCs), we have found that a subset of the proneural (PN) GSCs undergo transition to a mesenchymal (MES) state in a TNFa/NFkB dependent manner with an associated enrichment of CD44 sub-populations and radio-resistant phenotypes. To the contrary, MES GSCs exhibit constitutive NFkB activation, CD44 enrichment and radio-resistance. Patients whose tumors exhibit a higher MES metagene, increased expression of CD44, or activated NFkB were associated with poor radiation response and shorter survival. Our results indicate that NFkB activation mediated MES differentiation and radiation resistance presents an attractive therapeutic target for GBM. SIGNIFICANCE In this study, we show plasticity between the proneural (PN) and mesenchymal (MES) transcriptome signatures observed in glioblastoma (GBM). Specifically, we show that PN glioma sphere cultures (GSCs) can be induced to a MES state with an associated enrichment of CD44 expressing cells and a gain of radio-resistance, which we implicate as NFkB- dependent. Newly diagnosed GBM samples show a direct correlation between radiation response, higher MES metagene, CD44 expression, and NFkB activation. This correlation is also observed in the subset of GBM samples that do not exhibit IDH1 mutation, a favorable prognostic marker. Our results uncover a previously unknown link between subtype plasticity that is regulated by NFkB. Inhibition of NFkB activation can directly impact radio-resistance and presents an attractive therapeutic target for GBM. Gene expression data for 17 isolated Glioma Stem Cells

2013-08-15 | E-GEOD-49161 | biostudies-arrayexpress

Disruption of DNA Repair and Survival Pathways through Heat Shock Protein inhibition by Onalespib to Sensitize Malignant Gliomas to Chemoradiation therapy

Project description:Purpose: Proficient DNA repair by homologous recombination (HR) facilitates resistance to chemo-radiation in glioma stem cells (GSCs). We evaluated whether compromising HR by targeting HSP90, a molecular chaperone required for the function of key HR proteins, using onalespib, a long-acting, brain-penetrant HSP90 inhibitor, would sensitize high-grade gliomas to chemo-radiation in vitro and in vivoExperimental Design: The ability of onalespib to deplete HR client proteins, impair HR repair capacity, and sensitize GBM to chemo-radiation was evaluated in vitro in GSCs, and in vivo using zebrafish and mouse intracranial glioma xenograft models. The effects of HSP90 inhibition on the transcriptome and cytoplasmic proteins was assessed in GSCs and in ex vivo organotypic human glioma slice cultures.Results: Treatment with onalespib depleted CHK1 and RAD51, two key proteins of the HR pathway, and attenuated HR repair, sensitizing GSCs to the combination of radiation and temozolomide (TMZ). HSP90 inhibition reprogrammed the transcriptome of GSCs and broadly altered expression of cytoplasmic proteins including known and novel client proteins relevant to GSCs. The combination of onalespib with radiation and TMZ extended survival in a zebra fish and a mouse xenograft model of GBM compared to the standard of care (radiation and TMZ) or onalespib with radiation.Conclusions: The results of this study demonstrate that targeting HR by HSP90 inhibition sensitizes GSCs to radiation and chemotherapy and extends survival in zebrafish and mouse intracranial models of GBM. These results provide a preclinical rationale for assessment of HSP90 inhibitors in combination with chemoradiation in GBM patients.

2022-04-15 | GSE193635 | GEO

A Proneural to Mesenchymal Transition Mediated by NFkB Promotes Radiation Resistance in Glioblastoma (part 2)

2013-08-15 | E-GEOD-49162 | biostudies-arrayexpress

Glioma stem cell treatment with MELK-signaling inhibitors

Project description:Glioblastoma multiforme (GBM) is a highly lethal brain tumor. Due to resistance to current therapies, patient prognosis remains poor and development of novel and effective GBM therapy is crucial. Glioma stem cells (GSCs) have gained attention as therapeutic target in GBM due to their relative resistance to current therapies and potent tumor-initiating ability. Recent studies including our own identified that the mitotic kinase, maternal embryonic leucine-zipper kinase (MELK), is highly expressed in GBM tissues, specifically in GSCs, and its expression is inversely correlated with the post-surgical survival period of GBM patients. In addition, patient-derived GSCs depend on MELK for their survival and growth both in vitro and in vivo. Here, we provide evidence that the kinase activity of MELK is essential for the action of MELK in GSCs and vital for GBM growth. We utilized in silico structure-based analysis for protein-compound interaction to predict that a recently identified small molecule, Compound 1 (C1), binds to the kinase-active site of MELK protein and eliminates MELK kinase activity in nanomolar concentrations. When treated with C1, GSCs undergo mitotic arrest and subsequent cellular apoptosis in vitro, a phenotype identical to that observed using MELK shRNA-mediated knockdown. C1 treatment strongly induces tumor cell apoptosis in slice cultures of GBM surgical specimens and attenuates growth of mouse intracranial tumors derived from GSCs in a dose-dependent manner. Lastly, C1 treatment sensitizes GSCs to radiation treatment. Collectively, these data indicate that targeting MELK kinase activity is a promising approach to attenuate GBM growth by eliminating GSCs in tumors. Microarray-based expression analysis of glioma stem cells treated with MELK-signaling inhibitors

2013-08-28 | E-GEOD-50227 | biostudies-arrayexpress

POSTN secreted from GSCs promotes GSC self-renewal and tumor growth via activation of the αVβ3/PI3K/AKT/β-catenin/FOSL1 pathway [GSCs_RNA-seq]

Project description:Glioblastoma (GBM), classified as a grade 4 glioma, is the most prevalent intrinsic malignancy of the central nervous system. Glioblastoma stem cells (GSCs) are small populations of GBM cells with self-renewal and multilineage differentiation capabilities and are considered responsible for the tumorigenesis and development of GBM. GSCs also exhibit radiation resistance, chemoresistance, and angiogenic and invasive properties, which are correlated with poor outcomes in GBM patients. Therefore, targeting GSCs constitutes a promising approach for treating GBM patients. Our findings revealed that POSTN secreted from GSCs promotes GSC self-renewal and tumor growth via activation of the αVβ3/PI3K/AKT/β-catenin/FOSL1 pathway.

2024-08-01 | GSE273252 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data