Epigenetics and immune cells in medulloblastoma

Gorini, Francesca; Miceli, M.; Antonellis, Pasqualino de; Amente, Stefano; Zollo, Massimo; Ferrucci, Veronica

doi:10.3389/fgene.2023.1135404

Cited by 8 publications

(5 citation statements)

References 179 publications

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“…4D, and listed in Additional file 9). Thus, the use of this nutraceutical in a pill formula for systemic Ferrucci et al Journal of Translational Medicine (2024) 22:574 applications could be further envisioned as immunomodulant agent for the adjuvant therapy (during or after chemotherapeutics) with the aim to restore the innate immune response in those solid tumors characterized by immunosuppression driven by PI3K-Akt and TGF-β pathways dysregulation (e.g., brain tumors, medulloblastoma [117,118] and triple negative breast cancer [119]), once tested its pharmacokinetics and tissue biodistribution in vivo. Future studies will address this issue.…”

Section: Discussionmentioning

confidence: 99%

Modulation of innate immunity related genes resulting in prophylactic antimicrobial and antiviral properties

Ferrucci,

Miceli,

Pagliuca

et al. 2024

J Transl Med

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Background The innate immunity acts during the early phases of infection and its failure in response to a multilayer network of co-infections is cause of immune system dysregulation. Epidemiological SARS-CoV-2 infections data, show that Influenza Virus (FLU-A-B-C) and Respiratory Syncytial Virus (RSV) are co-habiting those respiratory traits. These viruses, especially in children (mostly affected by ‘multi-system inflammatory syndrome in children’ [MIS-C] and the winter pandemic FLU), in the aged population, and in ‘fragile’ patients are causing alteration in immune response. Then, bacterial and fungal pathogens are also co-habiting the upper respiratory traits (e.g., Staphylococcus aureus and Candida albicans), thus contributing to morbidity in those COVID-19 affected patients. Methods Liquid chromatography coupled with high-resolution mass spectrometry using the quadrupole orbital ion trap analyser (i.e., UHPLC-Q-Orbitrap HRMS) was adopted to measure the polyphenols content of a new nutraceutical formula (Solution-3). Viral infections with SARS-CoV-2 (EG.5), FLU-A and RSV-A viruses (as performed in BLS3 authorised laboratory) and real time RT-PCR (qPCR) assay were used to test the antiviral action of the nutraceutical formula. Dilution susceptibility tests have been used to estimate the minimum inhibitory and bactericidal concentration (MIC and MBC, respectively) of Solution-3 on a variety of microorganisms belonging to Gram positive/ negative bacteria and fungi. Transcriptomic data analyses and functional genomics (i.e., RNAseq and data mining), coupled to qPCR and ELISA assays have been used to investigate the mechanisms of action of the nutraceutical formula on those processes involved in innate immune response. Results Here, we have tested the combination of natural products containing higher amounts of polyphenols (i.e., propolis, Verbascum thapsus L., and Thymus vulgaris L.), together with the inorganic long chain polyphosphates ‘polyPs’ with antiviral, antibacterial, and antifungal behaviours, against SARS-CoV-2, FLU-A, RSV-A, Gram positive/ negative bacteria and fungi (i.e., Candida albicans). These components synergistically exert an immunomodulatory action by enhancing those processes involved in innate immune response (e.g., cytokines: IFNγ, TNFα, IL-10, IL-6/12; chemokines: CXCL1; antimicrobial peptides: HBD-2, LL-37; complement system: C3). Conclusion The prophylactic antimicrobial success of this nutraceutical formula against SARS-CoV-2, FLU-A and RSV-A viruses, together with the common bacteria and fungi co-infections as present in human oral cavity, is expected to be valuable.

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Section: Discussionmentioning

confidence: 99%

Modulation of innate immunity related genes resulting in prophylactic antimicrobial and antiviral properties

Ferrucci,

Miceli,

Pagliuca

et al. 2024

J Transl Med

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“…Moreover, the biomarkers with significant survival outcomes correlated with previously reported oncogenes. For example, the CBFA complex, which includes CBFA2T3 ( Hendrikse et al, 2022 ; Gorini et al, 2023 ), is suggested to play a critical role in tumor development through its interactions with epigenetic modifiers, contributing to the pathogenesis of medulloblastoma . Similarly, the study by Menyhárt et al (2019) demonstrated epigenetic changes in the RPTOR gene, along with other identified biomarkers, in classifying non-WNT/non-SHH medulloblastomas .…”

Section: Discussionmentioning

confidence: 99%

MBMethPred: a computational framework for the accurate classification of childhood medulloblastoma subgroups using data integration and AI-based approaches

Sharif Rahmani,

Lawarde,

Lingasamy

et al. 2023

Front. Genet.

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Childhood medulloblastoma is a malignant form of brain tumor that is widely classified into four subgroups based on molecular and genetic characteristics. Accurate classification of these subgroups is crucial for appropriate treatment, monitoring plans, and targeted therapies. However, misclassification between groups 3 and 4 is common. To address this issue, an AI-based R package called MBMethPred was developed based on DNA methylation and gene expression profiles of 763 medulloblastoma samples to classify subgroups using machine learning and neural network models. The developed prediction models achieved a classification accuracy of over 96% for subgroup classification by using 399 CpGs as prediction biomarkers. We also assessed the prognostic relevance of prediction biomarkers using survival analysis. Furthermore, we identified subgroup-specific drivers of medulloblastoma using functional enrichment analysis, Shapley values, and gene network analysis. In particular, the genes involved in the nervous system development process have the potential to separate medulloblastoma subgroups with 99% accuracy. Notably, our analysis identified 16 genes that were specifically significant for subgroup classification, including EP300, CXCR4, WNT4, ZIC4, MEIS1, SLC8A1, NFASC, ASCL2, KIF5C, SYNGAP1, SEMA4F, ROR1, DPYSL4, ARTN, RTN4RL1, and TLX2. Our findings contribute to enhanced survival outcomes for patients with medulloblastoma. Continued research and validation efforts are needed to further refine and expand the utility of our approach in other cancer types, advancing personalized medicine in pediatric oncology.

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“…The most common form of this is within the context of CpG islands, which are frequently found near the promoter region of genes. Methylation of these islands results in CpG island hypomethylation has also been revealed in medulloblastoma [7]. In the SHH subgroup, VAV1 is an oncogene that is hypomethylated, leading to an increase in expression and therefore tumorigenic potential [17].…”

Section: Introductionmentioning

confidence: 93%

Exploring the Molecular Complexity of Medulloblastoma: Implications for Diagnosis and Treatment

Rechberger,

Toll,

Vanbilloen

et al. 2023

Diagnostics

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Medulloblastoma is the most common malignant brain tumor in children. Over the last few decades, significant progress has been made in revealing the key molecular underpinnings of this disease, leading to the identification of distinct molecular subgroups with different clinical outcomes. In this review, we provide an update on the molecular landscape of medulloblastoma and treatment strategies. We discuss the four main molecular subgroups (WNT-activated, SHH-activated, and non-WNT/non-SHH groups 3 and 4), highlighting the key genetic alterations and signaling pathways associated with each entity. Furthermore, we explore the emerging role of epigenetic regulation in medulloblastoma and the mechanism of resistance to therapy. We also delve into the latest developments in targeted therapies and immunotherapies. Continuing collaborative efforts are needed to further unravel the complex molecular mechanisms and profile optimal treatment for this devastating disease.

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Epigenetics and immune cells in medulloblastoma

Cited by 8 publications

References 179 publications

Modulation of innate immunity related genes resulting in prophylactic antimicrobial and antiviral properties

Modulation of innate immunity related genes resulting in prophylactic antimicrobial and antiviral properties

MBMethPred: a computational framework for the accurate classification of childhood medulloblastoma subgroups using data integration and AI-based approaches

Exploring the Molecular Complexity of Medulloblastoma: Implications for Diagnosis and Treatment

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