Recent Advances in Glioma Cancer Treatment: Conventional and Epigenetic Realms

Fath, Mohsen Karami; Anjomrooz, Mehran; Jalalifar, Mohammadrasoul; Danial, Alizadeh, Seyed; Pourghasem, Z; Oshagh, Parisa Abbasi; Azargoonjahromi, Ali; Almasi, Faezeh; Manzoor, Hafza Zahira; Khalesi, Bahman; Pourzardosht, Navid; Khalili, Saeed; Payandeh, Zahra

doi:10.3390/vaccines10091448

Cited by 6 publications

(4 citation statements)

References 364 publications

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“…In our study, the reduction of H3K27me3 levels in OPCs with p53 deletion and PDGF-BB overexpression, by treatment with a well-recognized EZH2 inhibitor (Tazemetostat), significantly reduced the expression of genes regulating cell division, while increasing the expression of genes related to differentiation, thereby providing a molecular rationale to previous studies on the prognostic value of H3K27me3 56,57 . Our data are also consistent with the beneficial effect of reduced EZH2 activity on decreasing proliferation and reducing tumor growth in animal models 58,59,60 and decreasing proliferation and migration in adult human glioma cells 61 .…”

Section: Discussionsupporting

confidence: 89%

PDGF-BB overexpression in p53 null oligodendrocyte progenitors increases H3K27me3 and induces transcriptional changes which favor proliferation

Huang,

Mela,

Bhanu

et al. 2024

Preprint

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Proneural gliomas are brain tumors characterized by enrichment of oligodendrocyte progenitor cell (OPC) transcripts and genetic alterations. In this study we sought to identify transcriptional and epigenetic differences between OPCs with Trp53 deletion and PDGF-BB overexpression (BB-p53n), which form tumors when transplanted in mouse brains, and those carrying only p53 deletion (p53n), which do not. We used unbiased histone proteomics and RNA-seq analysis on these two genetically modified OPC populations and detected higher levels of H3K27me3 in BB-p53n compared to p53n OPCs. The BB-p53n OPC were characterized by higher levels of transcripts related to proliferation and lower levels of those related to differentiation. Pharmacological inhibition of histone H3K27 trimethylation in BB-p53n OPC reduced cell cycle transcripts and increased the expression of differentiation markers. These data suggest that PDGF-BB overexpression in p53 null OPC results in histone post-translational modifications and consequent transcriptional changes favoring proliferation while halting differentiation, thereby promoting the early stages of transformation.

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Section: Discussionsupporting

confidence: 89%

PDGF-BB overexpression in p53 null oligodendrocyte progenitors increases H3K27me3 and induces transcriptional changes which favor proliferation

Huang,

Mela,

Bhanu

et al. 2024

Preprint

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“…The p14 ARF gene is a tumor-suppressor gene involved in regulating cell proliferation and division [290,291], as well as tumor-induced angiogenesis [292,293]. When hypermethylation occurs in the p14 ARF gene, it leads to the inactivation of its tumor-suppressor functions, including the loss of p53 function and the deactivation of p21-mediated cell proliferation control [294].…”

Section: Cdkn2amentioning

confidence: 99%

“…This reduction in p16 INK4a levels can disrupt the normal regulation of the cell cycle, potentially leading to uncontrolled cell growth and an increased risk of developing cancer. The methylation rate of CDKN2A has been extensively studied in various types of cancer [291,301,302]. The reported incidence of p16 INK4a hypermethylation in OSCC can range from 23% to 76%.…”

Section: Cdkn2amentioning

confidence: 99%

Epigenetic Regulation in Oral Squamous Cell Carcinoma Microenvironment: A Comprehensive Review

Mesgari,

Esmaelian,

Nasiri

et al. 2023

Cancers

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Oral squamous cell carcinoma (OSCC) is a prevalent and significant type of oral cancer that has far-reaching health implications worldwide. Epigenetics, a field focused on studying heritable changes in gene expression without modifying DNA sequence, plays a pivotal role in OSCC. Epigenetic changes, encompassing DNA methylation, histone modifications, and miRNAs, exert control over gene activity and cellular characteristics. In OSCC, aberrant DNA methylation of tumor suppressor genes (TSG) leads to their inactivation, subsequently facilitating tumor growth. As a result, distinct patterns of gene methylation hold promise as valuable biomarkers for the detection of OSCC. Oral cancer treatment typically involves surgery, radiation therapy, and chemotherapy, but even with these treatments, cancer cells cannot be effectively targeted and destroyed. Researchers are therefore exploring new methods to target and eliminate cancer cells. One promising approach is the use of epigenetic modifiers, such as DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors, which have been shown to modify abnormal epigenetic patterns in OSCC cells, leading to the reactivation of TSGs and the suppression of oncogenes. As a result, epigenetic-targeted therapies have the potential to directly alter gene expression and minimize side effects. Several studies have explored the efficacy of such therapies in the treatment of OSCC. Although studies have investigated the efficacy of epigenetic therapies, challenges in identifying reliable biomarkers and developing effective combination treatments are acknowledged. Of note, epigenetic mechanisms play a significant role in drug resistance in OSCC and other cancers. Aberrant DNA methylation can silence tumor suppressor genes, while alterations in histone modifications and chromatin remodeling affect gene expression related to drug metabolism and cell survival. Thus, understanding and targeting these epigenetic processes offer potential strategies to overcome drug resistance and improve the efficacy of cancer treatments in OSCC. This comprehensive review focuses on the complex interplay between epigenetic alterations and OSCC cells. This will involve a deep dive into the mechanisms underlying epigenetic modifications and their impact on OSCC, including its initiation, progression, and metastasis. Furthermore, this review will present the role of epigenetics in the treatment and diagnosis of OSCC.

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“…Further, in preclinical studies, IFN-β has been reported to enhance the chemosensitivity towards TMZ by reducing transcription of MGMT [159]. It was also reported that the addition of IFN-β to standard chemoradiotherapy with TMZ (phase I clinical trial) was well tolerated and enhanced the survival of GBM patients [160], but no meaningful efficacy in cases of GBM or pediatric HGG, was noted after combined therapy with IFN-γ and radiotherapy or chemoradiotherapy [161].…”

Section: Immunotherapy and Clinical Trials In Gbm Malignancymentioning

confidence: 99%

Inflammatory Mediators and GBM Malignancy: Current Scenario and Future Prospective

Ulasov,

Singh,

Laevskaya

et al. 2023

Discovery Medicine

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Glioblastoma multiforme is one of the most widespread and dangerous forms of brain tumor with high inflammation. The tumor microenvironment comprises diverse tumor cells, different types of immune cells, and the extracellular matrix. Inflammatory mediators like chemokines, cytokines, and growth factors possibly serve as a capable therapeutic target to quash their tumorpromoting properties in glioblastoma multiforme (GBM). Cytokines are a heterogeneous group of soluble functional proteins which are also associated with the induction and progression of tumors. These are supposed to have both pro-inflammatory (such as tumor necrosis factor-α (TNF-α), interleukin-17A (IL-17A), interferon-γ (IFN-γ), IL-4, IL-2, IL-6, IL-12, IL-13) and antiinflammatory (such as transforming growth factor-β (TGF-β), IL-10, and granulocyte-macrophage colony-stimulating factor (GM-CSF)) actions and are the crucial communications channels in the tumor microenvironment. In the present minireview we discuss the tumor microenvironment and inflammatory mediators and focus on the involvement of cytokines in establishing communication with the tumor microenvironment. The presented data highlight the possible roles of cytokines in communication between glioblastoma cells and tumor microenvironment. Cytokines formed by immune cells protect the host organs while cytokines secreted by tumor cells are used for their advantage. Though the clinical trials with a number of immunotherapeutic agents are going on around the globe, there is still a requirement for thorough investigation of the regulatory mechanism managing GBM growth, recurrence, and tumor response to the therapy.

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Recent Advances in Glioma Cancer Treatment: Conventional and Epigenetic Realms

Cited by 6 publications

References 364 publications

PDGF-BB overexpression in p53 null oligodendrocyte progenitors increases H3K27me3 and induces transcriptional changes which favor proliferation

PDGF-BB overexpression in p53 null oligodendrocyte progenitors increases H3K27me3 and induces transcriptional changes which favor proliferation

Epigenetic Regulation in Oral Squamous Cell Carcinoma Microenvironment: A Comprehensive Review

Inflammatory Mediators and GBM Malignancy: Current Scenario and Future Prospective

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