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Conditionally Replicative Adenovirus as a Therapy for Malignant Peripheral Nerve Sheath Tumors

ABSTRACT: Conditionally Replicative Adenovirus as a Therapy for Malignant Peripheral Nerve Sheath Tumors

PROVIDER: PRJNA1033772 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26591100_1.fastq.gz	Fastqsanger.gz
	SRR26591100_2.fastq.gz	Fastqsanger.gz
	SRR26591101_1.fastq.gz	Fastqsanger.gz
	SRR26591101_2.fastq.gz	Fastqsanger.gz
	SRR26591102_1.fastq.gz	Fastqsanger.gz

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Conditionally Replicative Adenovirus as a Therapy for Malignant Peripheral Nerve Sheath Tumors

Project description:BACKGROUND: Conditionally replicative adenoviruses (CRAds) preferentially infect and lyse tumor cells. While CRAds have been clinically applied, their potential for neurofibromatosis type-1 associated malignant peripheral nerve sheath tumors (MPNSTs) remains unexplored. This study evaluates Cyclooxygenase 2 (COX2)-driven CRAds as a therapy for MPNST. METHODS: Viruses with wild type (WT) and modified fiber-knob domains were assessed for binding efficiency to the MPNST models. Viral infectivity, spread, and susceptibility of MPNST cells to oncolytic adenoviruses were assessed using both WT viruses or engineered CRAd constructs, with cell viability quantification. Tumor growth rates and survival probability of mice bearing human tumor xenografts or syngeneic allografts were assessed using intratumoral injections of CRAds. RESULTS: RGD-modified fibers exhibited improved binding to MPNST cells compared to non-cancer Schwann cells. vectors effectively replicated and lysed MPNST cells, displaying enhanced selectivity towards transformed cells. Tumor-bearing immunodeficient mice survived significantly longer when injected with CRAds compared to PBS controls, and immunocompetent models demonstrate robust infiltration of CD8+ T-cells. CONCLUSIONS: CRAds demonstrate selective binding and efficient replication in MPNST cells, leading to tumor cell lysis while sparing non-cancerous cells. These results suggest that oncolytic adenoviruses may have the potential as novel agents for MPNST therapy and thus warrant further investigation.

2024-04-24 | GSE246610 | GEO

Conditionally replicative adenovirus as a therapy for malignant peripheral nerve sheath tumors.

Project description:Oncolytic adenoviruses (Ads) stand out as a promising strategy for the targeted infection and lysis of tumor cells, with well-established clinical utility across various malignancies. This study delves into the therapeutic potential of oncolytic Ads in the context of neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumors (MPNSTs). Specifically, we evaluate conditionally replicative adenoviruses (CRAds) driven by the cyclooxygenase 2 (COX2) promoter, as selective agents against MPNSTs, demonstrating their preferential targeting of MPNST cells compared with non-malignant Schwann cell control. COX2-driven CRAds, particularly those with modified fiber-knobs exhibit superior binding affinity toward MPNST cells and demonstrate efficient and preferential replication and lysis of MPNST cells, with minimal impact on non-malignant control cells. In vivo experiments involving intratumoral CRAd injections in immunocompromised mice with human MPNST xenografts significantly extend survival and reduce tumor growth rate compared with controls. Moreover, in immunocompetent mouse models with MPNST-like allografts, CRAd injections induce a robust infiltration of CD8+ T cells into the tumor microenvironment (TME), indicating the potential to promote a pro-inflammatory response. These findings underscore oncolytic Ads as promising, selective, and minimally toxic agents for MPNST therapy, warranting further exploration.

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Methylation profiling of malignant peripheral nerve sheath tumour samples

Project description:Methylation profiling of malignant peripheral nerve sheath tumours (MPNSTs), epithelioid MPNSTs, sarcoma NOS, melanomas and spindle cell/sclerosing rhabdomyosarcomas.

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Comparative genomic hybridization of human malignant peripheral nerve sheath tumors and normal reference DNA

Project description:DNA copy number profiling of malignant peripheral nerve sheath tumours

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Malignant peripheral nerve sheath tumor (MPNST) tumor samples

Project description:Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma. Comprehensive proteomic profiles of 23 MPNST tumor specimens were obtained using LC-MS/MS. Among 23 tumor specimens, 13 patients showed favorable prognosis and 10 did local recurrence/distant metastasis.

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Comparison of modified rectus sheath nerve block and transverse abdominal fascia block in laparoscopic radical resection of colorectal cancer

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Canine Cutaneous Peripheral Nerve Sheath Tumours versus Fibrosarcomas can be Differentiated by Neuroectodermal Marker Genes in their Transcriptome.

Project description:The diagnostic differentiation of canine fibrosarcomas and peripheral nerve sheath tumors (PNST) is mainly based on their histopathologic phenotype. Histologic differentiation of these tumors can, however, be difficult and there is a lack of immunohistochemical markers to prove their histogenic origin. To identify possible PNST markers and to further investigate the histogenic origin of the two tumor types, we compared histologically defined canine fibrosarcomas and peripheral nerve sheath tumors by microarray analysis. Forty-five annotated gene products were significantly differentially expressed in both tumor types. Seven of these gene products, known to be specifically expressed in neuroectodermal tissues, showed higher expression in peripheral nerve sheath tumors: FMN2, KIF1B, GLI1, ROBO1, NMUR2, DOK4 and HMG20B. Furthermore, eight genes associated with carcinogenesis were up-regulated in fibrosarcomas: FHL2, PLAGL1, FNBP1L, BAG2, HK1, CSK and Cox5A. Comparison of the fibrosarcoma and PNST transcriptome therefore identified PNST phenotype-associated genes involved in neuroectodermal differentiation which may be potential PNST markers. Furthermore, the identified fibrosarcoma phenotype-associated genes may be potential markers to differentiate fibrosarcomas from other tumor types and may be involved in their pathogenesis. The aim of the present study was to examine the differences in global gene expression of histologically prototypic fibrosarcomas and PNST. To this end, complete transcriptome microarray analyses were used to quantify differences in gene expression activity in both tumor types.

2012-10-30 | E-GEOD-34382 | biostudies-arrayexpress

MicroRNA expression profiles in malignant peripheral nerve sheath tumors

Project description:MicroRNA expression profiles in malignant peripheral nerve sheath tumors

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Targeting RABL6A-RB1 signaling suppresses malignant peripheral nerve sheath tumors

Project description:Malignant peripheral nerve sheath tumors (MPNSTs) are deadly sarcomas that lack effective therapies. In most MPNSTs, the retinoblastoma (RB1) tumor suppressor is disabled by hyperactivation of cyclin dependent kinases (CDKs), commonly through loss of CDK inhibitory proteins such as p27(Kip1). RABL6A is an inhibitor of RB1 whose role in MPNSTs is unknown. To gain insight into MPNST development and establish new treatment options, we investigated RABL6A-RB1 signaling and CDK inhibitor-based therapy in MPNSTs.

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Canine Cutaneous Peripheral Nerve Sheath Tumours versus Fibrosarcomas can be Differentiated by Neuroectodermal Marker Genes in their Transcriptome.

2012-10-30 | GSE34382 | GEO