Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1066491 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Glioblastoma multiforme (GBM) treatment is a persistent challenge for oncologists, and this challenge has motivated the exploration of novel therapeutic strategies such as oncolytic virus therapy. Despite recent advancements in oncolytic virus therapy clinical trials for glioblastoma, a substantial number of patients have shown limited responses to this treatment. Here, we performed CRISPR‒Cas9 knockout screening and identified non-canonical BRG1/BRM-associated factor (ncBAF) complex as a pivotal determinant of oncolytic virus resistance. Knockout of the ncBAF-specific subunit Bromodomain-containing protein 9 (BRD9) markedly augmented the antitumor efficacy of oncolytic herpes simplex virus type 1 (oHSV1), as evidenced by our in vitro and in vivo studies. Mechanistically, BRD9 bound to RELA, a key transcription factor in the nuclear factor-κB (NF-κB) signaling pathway, to potentiate the expression of downstream antiviral genes. The application of a small molecule inhibitor targeting BRD9 (IBRD9) significantly enhanced oHSV1 activity against GBM across various models, including cell lines, patient-derived organoids, ex vivo cultured primary tumor slices, and mouse models. Moreover, reduced BRD9 levels correlated with improved patient outcomes in oHSV1 clinical trials. These findings highlight BRD9 as a prospective target for augmenting the effectiveness of oncolytic virus therapy against glioblastoma, providing insights for the development of novel combination treatments.
2025-07-29 | GSE260886 | GEO
Project description:BRD9 Dictates Oncolytic Virus Resistance in Glioblastoma
| PRJNA1083910 | ENA
Project description:The goal of the study was to determine whether photodynamic oncolytic virus therapy of glioblastoma and malignant meningioma xenografts in mice alters transciptomics associated with efficacy. RNA sequencing was used from tumors treated with PBS, laser, G47delta-KillerRed, and G47delta-KillerRed and laser, which is photodynamic oncolytic virus therapy.
2023-01-18 | GSE222895 | GEO
Project description:An acquisition of increased sensitivity of cancer cells to viruses is a common outcome of malignant progression that justifies the development of oncolytic viruses as anticancer therapeutics. Studying molecular changes that underlie the sensitivity to viruses would help to identify cases where oncolytic virus therapy would be most effective. We quantified changes in protein abundances in glioblastoma multiforme (GBM) and osteosarcoma cell lines that differ in the ability to induce resistance to vesicular stomatitis virus (VSV) infection in response to type I interferon (IFN) treatment. In IFN-treated samples we observed an up-regulation of protein products of some IFN-regulated genes (IRGs). In total, the proteome analysis revealed up to 20% more proteins encoded by IRGs in the glioblastoma cell line, which develops resistance to VSV infection after pre-treatment with IFN. In both cell lines protein-protein interaction and signaling pathway analyses have revealed a significant stimulation of processes related to type I IFN signaling and defense responses to viruses. The study has shown that the up-regulation of IRG proteins induced by the IFNα treatment of GBM cells can be detected at the proteome level. Similar analyses could be applied for revealing functional alterations within the antiviral mechanisms in glioblastoma samples, accompanying by acquisition of sensitivity to oncolytic viruses.
2022-06-09 | PXD022868 | Pride
Project description:We explored the utility of oncolytic virus therapy against glioblastoma with Zika virus (ZIKV), a flavivirus that induces cell death and differentiation of neural precursor cells in the developing fetus. ZIKV preferentially infected and killed glioblastoma stem cells (GSCs) relative to differentiated tumor progeny or normal neuronal cells. The effects against GSCs were not a general property of neurotropic flaviviruses, as West Nile Virus (WNV) indiscriminately killed both tumor and normal neural cells. ZIKV potently depleted patient-derived GSCs grown in culture and in organoids. Moreover, mice with glioblastoma survived substantially longer and at greater rates when the tumor was inoculated with a murine adapted strain of ZIKV. Our results suggest that ZIKV is an oncolytic virus that can preferentially target GSCs, and thus, genetically modified strains that further optimize safety could have therapeutic efficacy for adult glioblastoma patients.
2017-08-23 | GSE102244 | GEO
Project description:RNA N1-methyladenosine methylation (m1A) modification is critical in regulating mRNA translation and thus protein synthesis, but the role of m1A modification in the occurrence, progression, and immunotherapy of head and neck squamous cell cancer (HNSCC) remains largely unknown. In Tgfbr1/Pten 2cKO mice, we found that the spontaneous neoplastic transformation of oral mucosa is accompanied by elevated levels of m1A modification. Analysis of m1A-associated genes identified TRMT61A as the key m1A writer associated with cancer progression, and poor prognosis. Mechanically, TRMT61A-induced tRNA-m1A modification promotes MYC protein synthesis and subsequent programmed death-ligand 1 (PD-L1) expression. In Tgfbr1/Pten 2cKO mice, RNA-m1A modification levels are also elevated in tumors that developed resistance to oncolytic herpes simplex virus (oHSV) treatment. Therapeutic inhibition of m1A modification sustains oncolytic virus-induced antitumor immunity and reduces tumor growth, providing a promising strategy for alleviating resistance to oHSV therapy. These findings indicate that m1A inhibition can prevent immune escape after oHSV therapy by reducing the expression of PD-L1. Our results provide a mutually reinforcing strategy for clinical combination immunotherapy.
2024-03-31 | GSE247024 | GEO
Project description:Oncolytic virus therapy is a promising direction for cancer treatment. Numerous oncolytic viruses are under development or examined in clinical trials, there are examples of FDA approved virus vaccines. Although evident progress exists, oncolytic viruses still suffer low efficiency and the mechanisms of their action remain poorly understood. Defects in antiviral mechanisms that include type I interferon (IFN) signaling, contribute to sensitivity of malignant cells to oncolytic viruses, however, this sensitivity significantly differs for different malignant cells. In this project, we present a collection of representative transcriptomics and proteomics data for primary glioblastoma multiforme (GBM) cell cultures with established sensitivity to type I IFNs and the comprehensive characterization of GBM responses at both protein and RNA levels. Analysis demonstrated that GBM cells can respond to treatment by extreme upregulation of IFN-induced genes that is very similar to classic response in normal human cells. GBM cultures can significantly differ from each other by a value of transcriptome and proteome changes that are well correlated with sensitivity tests. In our data, upregulation of IFIT1/2/3, OAS1/2/3/L, MX1/2 among the others, was a reproducible marker for the developed resistance of GBM cells to vesicular stomatitis virus (VSV).
2021-12-29 | GSE163949 | GEO
Project description:Oncolytic virus therapy is a promising direction for cancer treatment. Numerous oncolytic virus strains are under development or examined in clinical trials, there are examples of FDA approved virus vaccines. Although evident progress exists, oncolytic viruses still suffer low efficiency and the mechanisms of their action remain poorly understood. Defects in antiviral mechanisms that include type I interferon (IFN) signaling, contribute to sensitivity of malignant cells to oncolytic viruses, however, this sensitivity significantly differs for different malignant cells. In this project, we present a collection of representative proteomics data for eight primary glioblastoma multiforme (GBM) cell cultures and one culture of normal astrocytes with established sensitivity to type I IFNs that comprehensively characterize the GBM cell responses to type I IFNs. Project consists of three parts: (1) label-free proteomics of primary GBM cultures on Orbitrap Fusion Lumos (a separate dataset); (2) label-free proteomics of primary GBM and normal astrocytes on Orbitrap QExactive HF; (3) label-based proteomics of wild type, IFIT3-deficient and PLSCR1-deficient DBTRG-05MG cells (ATCC) on Q-Exactive Plus.
2022-02-03 | PXD022906 | Pride
Project description:Oncolytic virus therapy is a promising direction for cancer treatment. Numerous oncolytic virus strains are under development or examined in clinical trials, there are examples of FDA approved virus vaccines. Although evident progress exists, oncolytic viruses still suffer low efficiency and the mechanisms of their action remain poorly understood. Defects in antiviral mechanisms that include type I interferon (IFN) signaling, contribute to sensitivity of malignant cells to oncolytic viruses, however, this sensitivity significantly differs for different malignant cells. In this project, we present a collection of representative proteomics data for eight primary glioblastoma multiforme (GBM) cell cultures and one culture of normal astrocytes with established sensitivity to type I IFNs that comprehensively characterize the GBM cell responses to type I IFNs. Project consists of three parts: (1) label-free proteomics of primary GBM cultures on Orbitrap Fusion Lumos; (2) label-free proteomics of primary GBM and normal astrocytes on Orbitrap QExactive HF; (3) label-based proteomics of wild type, IFIT3-deficient and PLSCR1-deficient DBTRG-05MG cells (ATCC) on Q-Exactive Plus.
2022-02-03 | PXD022836 | Pride
Project description:Most humans are infected with Epstein-Barr virus (EBV), a cancer-causing virus. While EBV generally persists silently in B lymphocytes, periodic lytic (re-)activation of latent virus is central to its life cycle and to most EBV-related diseases. However, a substantial fraction of EBV-infected B cells and tumor cells in a population is refractory to lytic activation. This resistance to lytic activation directly and profoundly impacts viral persistence and effectiveness of oncolytic therapy for EBV+ cancers. To identify the mechanisms that underlie susceptibility to EBV-lytic activation, we used host protein-expression profiling of separated-lytic and -refractory cells.
2016-07-22 | MSV000079993 | MassIVE