Development of gene expression signatures for glioblastoma stem-like cells infected with oncolytic virus
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PROVIDER: PRJNA649142 | ENA |
REPOSITORIES: ENA
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Project description:To further develop gene expression approach, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to identify oncolytic virus (OV) infection effect in different subpopulations of glioblastoma stem-like cells (G cells). Cells were transfected with either control or OV. OV affects gene expression patterns in cell subtype specific pattern.
2020-07-29 | GSE155247 | GEO
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: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
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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:We repoted the Glioblastoma stem cells(GSCs) infected by two strains of ZIKA virus, the Brazil and Dakar strains. The ZIKV was added into the medium of GSCs for 48 hours, the RNA was harvested after ZIKV infection. We found that the GSCs up-regulated the Type 1&2 interferons after infected by ZIKV
2017-08-23 | GSE102924 | GEO
Project description:Pancreatic cancer is a fatal disease associated with resistance to conventional therapies. GLV-1h153 is an oncolytic virus which has shown promise for the targeted treatment of cancer, and is engineered to carry the human sodium iodide symporter (hNIS) for the imaging of viral replication within tumors via enhanced uptake of several radionuclide probes. We used microarrays to determine changes in gene expression patterns over time associated with infection and susceptibility of pancreatic cancer cells to GLV-1h153. Understanding into the molecular mechanisms associated with PANC-1 sensitivity to GLV-1h153 may enable identification of cancers resistant to viral therapy, avoid undesirable side effects associated with the need for higher doses of viral treatment, and development of safer and more efficacious oncolytic virotherapies. PANC-1 cells were infected with GLV-1h153. Zero (T0), 6 (T6) and 24 (T24) hours after infection, 3 samples of each time point were harvested and gene expression patterns assessed using HG-U133A cDNA microarray chips as compared to uninfected control (T0).
2013-06-20 | E-GEOD-48121 | biostudies-arrayexpress
Project description:We used microarrays to identify genes regulated during oncolytic HSV infection. Oncolytic herpes simplex viruses (oHSV) are promising anticancer therapeutics. We sought to identify alterations in gene expression during oHSV infection of human cancer cells. Human malignant peripheral nerve sheath tumor (MPNST) cells were infected with G207, an ICP34.5-deleted oHSV previously evaluated in clinical trials. G207-infected cells demonstrated massive degradation of cellular mRNAs, while a subset were upregulated. A gene signature of 21 oHSV-induced genes contained 7 genes known to be HSV-induced. Go ontology classification revealed that a majority of upregulated genes are involved in Jak/STAT signaling, transcriptional regulation, nucleic acid metabolism, protein synthesis and apoptosis. Ingenuity-defined functional networks highlighted nodes for AP-1 subunits and interferon signaling via STAT1, SOCS1, SOCS3 and RANTES. Upregulation of SOCS1 correlated with sensitivity of MPNST lines to G207 and depletion of SOCS1 reduced virus replication >1-log. The transcriptome of oHSV-induced genes may predict oncolytic efficacy and provides rationale for next generation oncolytics. Experiment Overall Design: 5 human MPNST cancer cell lines were infected with G207 or mock infected for 6 hours followed by RNA extraction and hybridization on Affymetrix microarrays.
2008-06-16 | E-GEOD-8717 | biostudies-arrayexpress
Project description:Tumor-targeting oncolytic viruses engineered for glioblastoma immunotherapy
| PRJNA1021139 | ENA
Project description:Development of circRNA expression signatures for glioblastoma cells.
| PRJNA610620 | ENA