Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The Dopamine Receptor Antagonist TFP Prevents Phenotype Conversion and Improves Survival in Mouse Models of Glioblastoma

ABSTRACT: The Dopamine Receptor Antagonist TFP Prevents Phenotype Conversion and Improves Survival in Mouse Models of Glioblastoma

PROVIDER: PRJNA610246 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR11235862_1.fastq.gz	Fastqsanger.gz
	SRR11235862_2.fastq.gz	Fastqsanger.gz
	SRR11235863_1.fastq.gz	Fastqsanger.gz
	SRR11235863_2.fastq.gz	Fastqsanger.gz
	SRR11235864_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 48

Similar Datasets

The Dopamine Receptor Antagonist TFP Prevents Phenotype Conversion and Improves Survival in Mouse Models of Glioblastoma

Project description:Glioblastoma is the deadliest adult brain cancer and all patients ultimately succumb to the disease. Radiation therapy (RT) provides survival benefit of 6 months over surgery alone but these results have not improved in decades. We report that radiation induces a glioma-initiating cell phenotype and identified trifluoperazine (TFP) as a compound that interferes with this phenotype conversion. TFP caused loss of radiation-induced Nanog mRNA expression, activation of GSK3 with consecutive post-translational reduction in p-Akt, Sox2 and -catenin protein levels. TFP did not alter the intrinsic radiation sensitivity of glioma-initiating cells (GICs). Continuous treatment with TFP and a single dose of radiation reduced the number of GICs in vivo and prolonged survival in syngeneic and patient-derived orthotopic xenograft (PDOX) mouse models of glioblastoma. Our findings suggest that combination of a dopamine receptor antagonist with radiation enhances the efficacy of RT in glioblastoma by preventing radiation-induced phenotype conversion of radiosensitive non-GICs into treatment resistant, induced GICs.

2020-03-05 | GSE146358 | GEO

The dopamine receptor antagonist trifluoperazine prevents phenotype conversion and improves survival in mouse models of glioblastoma.

Project description:Glioblastoma (GBM) is the deadliest adult brain cancer, and all patients ultimately succumb to the disease. Radiation therapy (RT) provides survival benefit of 6 mo over surgery alone, but these results have not improved in decades. We report that radiation induces a glioma-initiating cell phenotype, and we have identified trifluoperazine (TFP) as a compound that interferes with this phenotype conversion. TFP causes loss of radiation-induced Nanog mRNA expression, and activation of GSK3 with consecutive posttranslational reduction in p-Akt, Sox2, and β-catenin protein levels. TFP did not alter the intrinsic radiation sensitivity of glioma-initiating cells (GICs). Continuous treatment with TFP and a single dose of radiation reduced the number of GICs in vivo and prolonged survival in syngeneic and patient-derived orthotopic xenograft (PDOX) mouse models of GBM. Our findings suggest that the combination of a dopamine receptor antagonist with radiation enhances the efficacy of RT in GBM by preventing radiation-induced phenotype conversion of radiosensitive non-GICs into treatment-resistant, induced GICs (iGICs).

| S-EPMC7245100 | biostudies-literature

A cyanobacterial LPS antagonist prevents endotoxin shock and blocks sustained TLR4 stimulation

Project description:A cyanobacterial LPS antagonist prevents endotoxin shock and blocks sustained TLR4 stimulation required for cytokine expression. We report the identification and biologic characterization of an LPS-like molecule extracted from the cyanobacterium Oscillatoria Planktothrix FP1 (CyP). Keywords: different ligands

2006-07-27 | GSE4748 | GEO

Transcription profiling of human dendritic monocytes treated with LPS (lipopolysaccharide) or CyP (Cyanobacterial Product) reveals cyanobacterial LPS antagonist prevents endotoxin shock and blocks sustained TLR4 stimulation required for cytokine expression

2007-10-26 | E-GEOD-4748 | biostudies-arrayexpress

The TBK1/IKKe Inhibitor Amlexanox Improves Dyslipidemia and Prevents Atherosclerosis

Project description:The TBK1/IKKe Inhibitor Amlexanox Improves Dyslipidemia and Prevents Atherosclerosis

| PRJNA861838 | ENA

AhR antagonist

Project description:AhR antagonist

| PRJNA766233 | ENA

NLRP3-inflammasome suppression improves longevity and prevents cardiac aging in mice

Project description:NLRP3-inflammasome suppression improves longevity and prevents cardiac aging in mice

| PRJNA512138 | ENA

3D Model Enhances Human Glia conversion to Neurons with Dopaminergic Functional and Molecular Traits Or: 3D Model Enhances Human Glia conver-sion to Induced Dopamine Neurons?

Project description:Parkinson’s disease (PD), a prevalent neurodegenerative disorder, is primarily characterized by progressive loss of ventral midbrain dopamine (DA) neurons. This focal degeneration makes PD suitable for cell replacement therapies and clinical trials using stem cell derived-DA neurons are ongoing. An emerging alternative to cell transplantation for brain repair is in vivo reprogramming, where resident glia is converted into neurons directly inside the brain. While functional neurons with potential therapeutic effects can be obtained via in vivo conversion in rodent studies, translating this to relevant human pre-clinical models has been limited to two-dimensional (2D) cultures. To mimic three-dimensional (3D) complexity and approximate in vivo-like conversion, we developed a 3D model for human glia conversion. Our model promotes neural conversion and generates functionally mature DA neurons at a faster pace than in 2D. Molecular profiling, single-nucleus transcriptomics and lineage tracing mapped glia heterogeneity, provided mechanistic insights of the reprogramming process and defined neuronal identity after conversion. Our results emphasize the advantages of utilizing 3D models as a reproducible and con-sistent platform for reprogramming studies.

2024-10-15 | GSE242076 | GEO

The dopamine transporter antiports potassium to increase the uptake of dopamine

Project description:The dopamine transporter facilitates dopamine reuptake from the extracellular space to terminate neurotransmission. The transporter belongs to the neurotransmitter:sodium symporter family, which includes transporters for serotonin, norepinephrine, and GABA that utilize the Na+ gradient to drive the uptake of substrate. Decades ago, it was shown that the serotonin transporter also antiports K+, but investigations of K+-coupled transport in other neurotransmitter:sodium symporters have been inconclusive. Here, we show that ligand binding to the drosophila- and human dopamine transporters are inhibited by K+, and the conformational dynamics of the drosophila dopamine transporter in K+ are divergent from the apo- and Na+-states. Furthermore, we found that K+ increased dopamine uptake by the drosophila dopamine transporter in liposomes, and visualized Na+ and K+ fluxes in single proteoliposomes using fluorescent ion indicators. Our results expand on the fundamentals of dopamine transport and prompt a reevaluation of the impact of K+ on other transporters in this pharmacologically important family.

2022-05-20 | PXD032663 | Pride

Mannose alters gut microbiome, prevents diet induced obesity and improves host metabolism

Project description:Mannose alters gut microbiome, prevents diet induced obesity and improves host metabolism

| PRJNA434573 | ENA