Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Endocan-PDGFRα mediated signaling drives glioblastoma spatial heterogeneity and influences tumor vasculature/radioresistance

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE137809 | GEO | 2023/09/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Endocan-PDGFRα mediated signaling drives glioblastoma spatial heterogeneity and influences tumor vasculature/radioresistance [ATAC-seq]

Project description:The goal of this project was to study the difference in GBM tumors formed in ESM1 Knockout vs. WT mice.

2023-09-01 | GSE137796 | GEO

Endocan-PDGFRα mediated signaling drives glioblastoma spatial heterogeneity and influences tumor vasculature/radioresistance [RNA-seq]

Project description:The goal of this project was to study the difference in GBM tumors formed in ESM1 Knockout vs. WT mice.

2023-09-01 | GSE137808 | GEO

Endocan-PDGFRα mediated signaling drives glioblastoma spatial heterogeneity and influences tumor vasculature/radioresistance

Project description:Endocan-PDGFRα mediated signaling drives glioblastoma spatial heterogeneity and influences tumor vasculature/radioresistance

| PRJNA573099 | ENA

Endocan-PDGFRα mediated signaling drives glioblastoma spatial heterogeneity and influences tumor vasculature/radioresistance [ATAC-seq]

Project description:Endocan-PDGFRα mediated signaling drives glioblastoma spatial heterogeneity and influences tumor vasculature/radioresistance [ATAC-seq]

| PRJNA573085 | ENA

Endocan-PDGFRα mediated signaling drives glioblastoma spatial heterogeneity and influences tumor vasculature/radioresistance [RNA-seq]

Project description:Endocan-PDGFRα mediated signaling drives glioblastoma spatial heterogeneity and influences tumor vasculature/radioresistance [RNA-seq]

| PRJNA573102 | ENA

Targeting PDGFRα-activated glioblastoma through specific inhibition of SHP-2-mediated signaling.

Project description:BackgroundGlioblastoma (GBM) is the most malignant primary brain tumor, with dismal median survival. Treatment of GBM is particularly challenging given the intrinsic resistance to chemotherapy and difficulty of drugs to reach the tumor beds due to the blood-brain barrier. Here, we examined the efficacy of SHP099, a potent, selective, and oral SHP-2 inhibitor for treating GBM with activated platelet derived growth factor receptor alpha (PDGFRα) signaling.MethodsThe effects of SHP099 on cell survival of neural progenitor cells (NPCs), GBM cell lines, and patient-derived glioma stem-like cells (GSCs) were evaluated. Brain and plasma pharmacokinetics of SHP099 and its ability to inhibit SHP-2 signaling were assessed. SHP099 efficacy as a single agent or in combination with temozolomide (TMZ) was assessed using transformed mouse astrocyte and GSC orthotopic xenograft models.ResultsActivated PDGFRα signaling in established GBM cells, GSCs, and transformed mouse astrocytes was significantly inhibited by SHP099 compared with NPCs in vitro and in vivo through targeting SHP-2-stimulated activation of extracellular signal-regulated protein kinases 1 and 2 in GBM. SHP099 treatment specifically inhibited expression of JUN, a downstream effector of PDGFR signaling, thereby attenuating cell cycle progression in GBM cells with activated PDGFRα. Moreover, SHP099 accumulated at efficacious concentrations in the brain and effectively inhibited orthotopic GBM tumor xenograft growth. SHP099 exhibited antitumor activity either as a single agent or in combination with TMZ and provided significant survival benefits for GBM tumor xenograft-bearing animals.ConclusionsOur data demonstrate the utility and feasibility of SHP099 as a potential therapeutic option for improving the clinical treatment of GBM in combination with TMZ.

| S-EPMC6827835 | biostudies-literature

Endothelial-secreted Endocan protein activates PDGFRa signaling and regulates vascularity, radioresistance, and regional phenotype in glioblastoma

Project description:Extensive neovascularization is a hallmark of glioblastoma (GBM). In addition to supplying oxygen and nutrients, vascular endothelial cells provide trophic support to GBM cells via paracrine signaling. Here we report that Endocan (ESM1), an endothelial-secreted proteoglycan, confers enhanced proliferative, migratory, and angiogenic properties to GBM cells and regulates their spatial identity. Mechanistically, Endocan exerts at least part of its functions via direct binding and activation of the PDGFRA receptor. Subsequent downstream signaling enhances chromatin accessibility of the Myc promoter and upregulates Myc expression inducing stable phenotypic changes in GBM cells. Furthermore, Endocan confers a radioprotection phenotype in GBM cells, both in vitro and in vivo. Inhibition of Endocan-PDGFRA signaling with ponatinib increases survival in the Esm1 wild-type but not in the Esm1 knock-out mouse GBM model. Our findings identify Endocan and its downstream signaling axis as a potential target to subdue GBM recurrence and highlight the importance of vascular-tumor interactions for GBM development.

2024-12-04 | PXD057635 | Pride

IFI16-mediated cellular senescence drives HMOX1-dependent evasion of ferroptosis and radioresistance in glioblastoma

Project description:Glioblastoma multiforme (GBM) is a persistent challenge in oncology due to its aggressive nature and limited survival. Despite various therapeutic strategies, the recurrence of GBM still exists, driven by the complex cellular diversity and evolutionary dynamics during the treatment process. This study established a radioresistant GBM cell model through repeated exposure to ionizing radiation and revealed a distinct manifestation of cellular senescence of these cells. The comprehensive genomic and transcriptomic analyses identified that IFI16, as a critical driver of cellular senescence, contributed to the radioresistance of GBM. Mechanistically, IFI16 was involved in orchestrating HMOX1 transcription thereby attenuating ferroptosis after irradiation. HMOX1 limited lipid peroxidation, reactive oxygen species (ROS) production, and intracellular Fe2+ content following irradiation, thus effectively counteracting ferroptosis in GBM. Furthermore, IFI16 interacted with the transcription factors JUND and SP1 through its pyrin domain, robustly facilitating HMOX1 expression, further inhibiting ferroptosis and enhancing radioresistance in GBM cells. Notably, glyburide, an anti-aging agent, effectively disrupted IFI16 function and thus enhanced ferroptosis and radiosensitivity. By specifically targeting the pyrin domain of IFI16, glyburide emerged as a potential therapeutic agent against GBM radioresistance. In conclusion, these novel findings underscored the central role of IFI16 in GBM radioresistance and offered promising avenues for innovative therapeutic interventions against GBM radiosensitivity

2024-12-25 | GSE274090 | GEO

Visualising spatial heterogeneity in glioblastoma using imaging habitats.

Project description:Glioblastoma is a high-grade aggressive neoplasm characterised by significant intra-tumoral spatial heterogeneity. Personalising therapy for this tumour requires non-invasive tools to visualise its heterogeneity to monitor treatment response on a regional level. To date, efforts to characterise glioblastoma's imaging features and heterogeneity have focussed on individual imaging biomarkers, or high-throughput radiomic approaches that consider a vast number of imaging variables across the tumour as a whole. Habitat imaging is a novel approach to cancer imaging that identifies tumour regions or 'habitats' based on shared imaging characteristics, usually defined using multiple imaging biomarkers. Habitat imaging reflects the evolution of imaging biomarkers and offers spatially preserved assessment of tumour physiological processes such perfusion and cellularity. This allows for regional assessment of treatment response to facilitate personalised therapy. In this review, we explore different methodologies to derive imaging habitats in glioblastoma, strategies to overcome its technical challenges, contrast experiences to other cancers, and describe potential clinical applications.

| S-EPMC9731157 | biostudies-literature

TRAF4-mediated ubiquitination-dependent activation of JNK/Bcl-xL drives radioresistance.

Project description:The E3 ligase TNF receptor-associated factor 4 (TRAF4) is upregulated and closely associated with tumorigenesis and the progression of multiple human malignancies. However, its effect on radiosensitivity in colorectal cancer (CRC) has not been elucidated. The present study found that TRAF4 was significantly increased in CRC clinical tumor samples. Depletion of TRAF4 impaired the malignant phenotype of CRC cells and sensitized irradiation-induced cell death. Irradiation activated the c-Jun N-terminal kinases (JNKs)/c-Jun signaling via increasing JNKs K63-linked ubiquitination and phosphorylation. Furthermore, c-Jun activation triggered the transcription of the antiapoptotic protein Bcl-xL, thus contributing to the radioresistance of CRC cells. TRAF4 was positively correlated with c-Jun and Bcl-xL, and blocking TRAF4 or inhibiting Bcl-xL with inhibitor markedly promoted ionizing radiation (IR)-induced intrinsic apoptosis and sensitized CRC cells to radiotherapy in vitro and in vivo. Our findings illustrate a potential mechanism of radioresistance, emphasizing the clinical value of targeting the TRAF4/Bcl-xL axis in CRC therapy.

| S-EPMC9918491 | biostudies-literature

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