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Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models

ABSTRACT: Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models

PROVIDER: PRJNA947121 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23928829_1.fastq.gz	Fastqsanger.gz
	SRR23928829_2.fastq.gz	Fastqsanger.gz
	SRR23928830_1.fastq.gz	Fastqsanger.gz
	SRR23928830_2.fastq.gz	Fastqsanger.gz
	SRR23928831_1.fastq.gz	Fastqsanger.gz

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Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models

Project description:Mice with orthotopic tongue cancer received neoadjuvant G47Δ therapy. Neoadjuvant G47Δ and resection led to 10/10 survival even with insufficient resection margins.

2023-04-13 | GSE227813 | GEO

Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models.

Project description:A complete resection of tongue cancer is often difficult. We investigate the usefulness of administering G47Δ (teserpaturev), a triple-mutated oncolytic herpes simplex virus type 1, prior to resection. G47Δ exhibits good cytopathic effects and replication capabilities in all head and neck cancer cell lines tested. In an orthotopic SCCVII tongue cancer model of C3H/He mice, an intratumoral inoculation with G47Δ significantly prolongs the survival. Further, mice with orthotopic tongue cancer received neoadjuvant G47Δ (or mock) therapy with or without "hemilateral" resection, the maximum extent avoiding surgical deaths. Neoadjuvant G47Δ and resection led to 10/10 survival (120 days), whereas the survivals for G47Δ alone and resection alone were 6/10 and 5/10, respectively: all control animals died by day 11. Furthermore, 100% survival was achieved with neoadjuvant G47Δ therapy even when the resection area was narrowed to "partial," providing insufficient resection margins, whereas hemilateral resection alone caused death by local recurrence in half of the animals. G47Δ therapy caused increased number of tumor-infiltrating CD8+ and CD4+ cells, increased F4/80+ cells within the residual tongues, and increased expression of immune-related genes in and around the tumor. These results imply that neoadjuvant use of G47Δ is useful for preventing local recurrence after tongue cancer surgery.

| S-EPMC10423690 | biostudies-literature

Histone deacetylase inhibitors (HDACi) enhance oncolytic herpes simplex virus in malignant meningioma.

Project description:The goal of the study was to determine whether low dose HDACi sensitizes human malignant meningioma cells to the cytotoxic capacity of oncolytic herpes simplex virus G47delta. RNA sequencing was used to examine transcriptomic changes mediated by HDACi preexposure before oncolytic virus infection.

2022-08-02 | GSE210178 | GEO

Histone deacetylase inhibitors (HDACi) enhance oncolytic herpes simplex virus in malignant meningioma.

Project description:Histone deacetylase inhibitors (HDACi) enhance oncolytic herpes simplex virus in malignant meningioma.

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Transcription profiling of human MPNST cancer cells infected with G207 an oncolytic HSV

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.

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Single-cell RNA sequencing reveals a strong connection between Gadd45g upregulation and oncolytic HSV infection in tumor tissue

Project description:The oncolytic effect of virotherapy derives from the intrinsic capability of the applied virus in selectively infecting and killing tumor cells. Although oncolytic viruses of various constructions have been shown to efficiently infect and kill tumor cells in vitro, the efficiency of these viruses to exert the same effect on tumor cells within tumor tissues in vivo has not been extensively investigated. Here we report our studies using single-cell RNA sequencing to comprehensively analyze the gene expression profile of tumor tissues following herpes simplex virus 2-based oncolytic virotherapy. Our data revealed the extent and cell types within the tumor microenvironment that could be infected by the virus. Moreover, we observed changes in the expression of cellular genes, including antiviral genes, in response to viral infection. One notable gene found to be upregulated significantly in oncolytic virus-infected tumor cells was Gadd45g, which is desirable for optimal virus replication. These results not only help reveal the precise infection status of the oncolytic virus in vivo, but also provide insight that may lead to the development of new strategies to further enhance the therapeutic efficacy of oncolytic virotherapy.

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Gene expression in human recurrent glioblastoma before and after inoculation with the oncolytic herpes simplex virus G207 using NanoString pancancer immune profiling gene expression panel

Project description:We have previously developed the use of genetically engineered herpes simplex virus type 1 (G207) for the experimental treatment of malignant glioma (PMID: 18957964). We demonstrated that G207 propagates in and kills nervous system tumor cells with little to no evidence of viral encephalitis. Here, six adult patients with recurrent glioblastoma were recruited onto a phase 1b clinical trial to test safety and efficacy of G207 in anti-tumor response. We obtained resected tumor tissue before and after (within 2-5 days) inoculation with G207. RNA was extracted from all tissues and subject to gene expression profiling using NanoString Pancancer Immune panel. Our data indicate in the post-G207 samples that interferon immune response and the subsequent recruitment of an adaptive immune response strongly associated with overall survival after inoculation with oncolytic virus G207 in patients with recurrent malignant glioma.

2021-12-31 | GSE164104 | GEO

Expression data from Human MPNST cancer cells infected with G207 and oncolytic HSV

2007-08-08 | GSE8717 | GEO

Gene expression in human recurrent glioblastoma before and after inoculation with the oncolytic herpes simplex virus G207

Project description:Gene expression in human recurrent glioblastoma before and after inoculation with the oncolytic herpes simplex virus G207

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Resistance of primary ovarian cancer cells to oncolytic adenoviruses

Project description:This SuperSeries is composed of the following subset Series: GSE15350: Resistance of primary ovarian cancer cells to oncolytic adenoviruses part1 of 2 GSE15351: Resistance of primary ovarian cancer cells to oncolytic adenoviruses part2 of 2 Refer to individual Series

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