Principles in the Management of Glioblastoma

Genes, Год журнала: 2024, Номер 15(4), С. 501 - 501

Опубликована: Апрель 17, 2024

Glioblastoma, the most aggressive and common malignant primary brain tumour, is characterized by infiltrative growth, abundant vascularization, clinical evolution. Patients with glioblastoma often face poor prognoses, a median survival of approximately 15 months. Technological progress subsequent improvement in understanding pathophysiology these tumours have not translated into significant achievements therapies or outcomes for patients. Progress molecular profiling has yielded new omics data more refined classification glioblastoma. Several typical genetic epigenetic alterations include mutations genes regulating receptor tyrosine kinase (RTK)/rat sarcoma (RAS)/phosphoinositide 3-kinase (PI3K), p53, retinoblastoma protein (RB) signalling, as well mutation isocitrate dehydrogenase (IDH), methylation O6-methylguanine-DNA methyltransferase (MGMT), amplification epidermal growth factor vIII, codeletion 1p/19q. Certain microRNAs, such miR-10b miR-21, also been identified prognostic biomarkers. Effective treatment options are limited. Surgery, radiotherapy, alkylating agent chemotherapy remain pillars treatment. Only promoter gene MGMT predicts benefit from temozolomide it guides choice first-line elderly targeted strategies based on tumour-intrinsic dominant signalling pathways antigenic tumour profiles under investigation trials. This review explores potential biomarkers that could be deployed analytical tools diagnosis prognostication Recent advancements treating discussed, along liquid biopsies to advance personalized medicine field glioblastoma, highlighting challenges promises future.

Язык: Английский

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CRISPR/Cas9-Mediated Gene Therapy for Glioblastoma: A Scoping Review

Biomedicines, Год журнала: 2024, Номер 12(1), С. 238 - 238

Опубликована: Янв. 21, 2024

This scoping review examines the use of CRISPR/Cas9 gene editing in glioblastoma (GBM), a predominant and aggressive brain tumor. Categorizing targets into distinct groups, this explores their roles cell cycle regulation, microenvironmental dynamics, interphase processes, therapy resistance reduction. The complexity CRISPR-Cas9 applications GBM research is highlighted, providing unique insights apoptosis, proliferation, immune responses within tumor microenvironment. studies challenge conventional perspectives on specific genes, emphasizing potential therapeutic implications manipulating key molecular players dynamics. Exploring GBMs yields significant regulation cellular spanning interphase, renewal, migration. Researchers, by precisely targeting uncover orchestration governing growth, differentiation during critical phases cycle. findings underscore technology unraveling complex dynamics microenvironment, offering promising avenues for targeted therapies to curb growth. also outlines addressing GBM, employing target genes associated with chemotherapy resistance, showcasing its transformative effective treatments.

Язык: Английский

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Prognostic Values of Systemic Inflammatory Immunological Markers in Glioblastoma: A Systematic Review and Meta-Analysis

Cancers, Год журнала: 2023, Номер 15(13), С. 3339 - 3339

Опубликована: Июнь 25, 2023

Neutrophils are an important part of the tumor microenvironment, which stimulates inflammatory processes through phagocytosis, degranulation, release small DNA fragments (cell-free DNA), and presentation antigens. Since neutrophils accumulate in peripheral blood patients with advanced-stage cancer, a high neutrophil-to-lymphocyte ratio can be biomarker poor prognosis glioblastoma. The present study aimed to explore prognostic value preoperative levels (NLR), platelet-to-lymphocyte (PLR), systemic immune inflammation index (SII), response (SIRI), cell-free (cfDNA) better predict implications survival rate glioblastoma patients.The meta-analysis was carried out according recommendations standards established by Preferred Reporting Items for Systematic Reviews Meta-Analyses. Databases PubMed, EBSCO, Medline were systematically searched select all relevant studies published up December 2022.Poorer prognoses recorded NLR or PLR when compared low (HR 1.51, 95% CI 1.24-1.83, p < 0.0001 HR 1.34, 1.10-1.63, 0.01, respectively). Similarly, worse reported higher cfDNA 2.35, 1.27-4.36, 0.01). SII SIRI values not related (p = 0.0533 0.482, respectively).Thus, NLR, PLR, cfDNA, unlike SIRI, appeared useful convenient markers assess

Язык: Английский

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EZH2-Myc driven glioblastoma elicited by cytomegalovirus infection of human astrocytes

Oncogene, Год журнала: 2023, Номер 42(24), С. 2031 - 2045

Опубликована: Май 5, 2023

Abstract Mounting evidence is identifying human cytomegalovirus (HCMV) as a potential oncogenic virus. HCMV has been detected in malignant gliomas. EZH2 and Myc play role, correlating with the glioma grade. Herewith, we present first experimental for reprogramming vector, straight through dedifferentiation of mature astrocytes, generation CMV-Elicited Glioblastoma Cells (CEGBCs) possessing glioblastoma-like traits. counterparts progression perceived cellular molecular mechanisms succeeding transformation invasion processes CEGBCs involved spheroid formation invasiveness. multiforme (GBM) biopsies were characterized by an elevated expression, strong positive correlation between aforementioned markers presence HCMV. From GBM tissues, isolated clinical strains that transformed HAs toward exhibiting upregulated Myc. Spheroids generated from possessed sensitive to inhibitor, ganciclovir, temozolomide triple therapy. transform fit HCMV-induced glioblastoma model oncogenesis, supports tumorigenic properties which might be highly pertinent pathophysiology astrocytic brain tumors thereby paving way new therapeutic strategies.

Язык: Английский

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The Current Landscape of Glioblastoma Biomarkers in Body Fluids

Cancers, Год журнала: 2023, Номер 15(15), С. 3804 - 3804

Опубликована: Июль 26, 2023

Glioblastoma (GBM) is a highly aggressive and lethal primary brain cancer that necessitates early detection accurate diagnosis for effective treatment improved patient outcomes. Traditional diagnostic methods, such as imaging techniques tissue biopsies, have limitations in providing real-time information distinguishing treatment-related changes from tumor progression. Liquid used to analyze biomarkers body fluids, offer non-invasive dynamic approach detecting monitoring GBM. This article provides an overview of GBM including circulating cells (CTCs), cell-free DNA (cfDNA), RNA (cfRNA), microRNA (miRNA), extracellular vesicles. It explores the clinical utility these detection, monitoring, prognosis. Challenges implementing liquid biopsy strategies practice are also discussed. The highlights potential biopsies valuable tools personalized management but underscores need standardized protocols further research optimize their utility.

Язык: Английский

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Advances on Liquid Biopsy Analysis for Glioma Diagnosis

Biomedicines, Год журнала: 2023, Номер 11(9), С. 2371 - 2371

Опубликована: Авг. 24, 2023

Gliomas comprise the most frequent primary central nervous system (CNS) tumors, characterized by remarkable genetic and epigenetic heterogeneity, difficulty in monitoring, increased relapse mortality rates. Tissue biopsy is an established method of tumor cell collection analysis that enables diagnosis, classification different types, prediction prognosis upon confirmation tumor's location for surgical removal. However, it invasive often challenging procedure cannot be used patient screening, detection mutations, disease or resistance to therapy. To this end, minimally liquid has emerged, allowing effortless sampling enabling continuous monitoring. It considered a novel preferable way obtain faster data on potential risk, personalized prognosis, recurrence evaluation. The purpose review describe advances glioma diagnosis management, indicating several biomarkers can utilized analyze characteristics, such as cell-free DNA (cfDNA), RNA (cfRNA), circulating proteins, cells (CTCs), exosomes. further addresses benefit combining with radiogenomics facilitate early accurate diagnoses, enable precise prognostic assessments, real-time aiming towards more optimal treatment decisions.

Язык: Английский

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Chitosan-PLGA mucoadhesive nanoparticles for gemcitabine repurposing for glioblastoma therapy

European Journal of Pharmaceutics and Biopharmaceutics, Год журнала: 2024, Номер 200, С. 114326 - 114326

Опубликована: Май 15, 2024

Glioblastoma (GBM) is a highly deadly brain tumor that does not respond satisfactorily to conventional treatment. The non-alkylating agent gemcitabine (GEM) has been proposed for treating GBM. It can overcome MGMT protein-mediated resistance, major limitation of therapy with the alkylating temozolomide (TMZ). However, GEM's high systemic toxicity and poor permeability across blood-brain barrier (BBB) pose significant challenges its delivery brain. Thus, mucoadhesive poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) coated chitosan (CH), suitable intranasal GEM delivery, were in this work. A central composite design (CCD) was implemented NPs optimization, appropriate characteristics administration obtained. vitro studies revealed possess excellent properties ability selectively release simulated tissue environment. using two human GBM cell lines (U215 T98G) NPs' promote antiproliferative activity sensitize cells effect TMZ. findings work demonstrate developed CH-GEM-NPs are systems GEM, both as single chemosensitizer gold standard therapy.

Язык: Английский

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ABORDAGENS ATUAIS PARA DIAGNÓSTICO E PROGNÓSTICO DO GLIOBLASTOMA

Revista Foco, Год журнала: 2025, Номер 18(1), С. e7399 - e7399

Опубликована: Янв. 7, 2025

Os gliomas são conjuntos de tumores do Sistema Nervoso Central que atacam as células gliais sendo o glioblastoma multiforme (GBM) a neoplasia primária maligna mais comum, possuindo uma baixa taxa sobrevivência dos pacientes diagnosticados. Tendo em consideração gravidade desse glioma, importância diagnóstico precoce e perspectivas tratamento foram analisadas obras literárias natureza científica, sínteses literatura documentos científicos para realização desta pesquisa bem como pesquisas clínicas, revisões documentais, trabalhos monográficos conclusão curso publicados entre 2015 2023 ao tange comportamento biológico glioblastomas, biomarcadores, biópsia líquida, tomografia computadorizada ressonância magnética. Concernente rastreamento enfatizar líquida por sua efetividade localizar no sangue, urina ou demais fluidos corporais fragmentos DNA tumoral liberados sangue reconhecida padrão doentes oncológicos. Quanto destacasse magnética nuclear com uso contraste gadolínio detectar características típicas nas sequências. Este trabalho auxilia na consolidação conhecimento já adquirido sugere caminhos promissores estudos futuros, enfatizando relevância da contínua sobre Glioblastoma Multiforme.

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Levels of Proangiogenic Molecules and Terminal Complement Complex C5b-9 in the Crown of Circulating sEVs in Patients with Recurrent Glioblastomas: Relationship with Tumor Molecular Characteristics

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(2), С. 132 - 132

Опубликована: Фев. 18, 2025

Circulating small extracellular vesicles (sEVs) are emerging as potential biomarkers for glioblastoma progression. This study aimed to compare the levels of matrix metalloproteinases (MMP2 and MMP9), terminal complement complex (C5b-9), VEGF-A in circulating sEVs patients (GBMPs) with without tumor recurrence. Using differential ultracentrifugation, were isolated from blood samples GBMPs no recurrence over one year (n = 6) after first relapse 14). The characterized quantified using flow cytometry. In both groups, C5b-9 was predominantly detected on tumor-specific (glial fibrillary acidic protein (GFAP)-positive sEVs) high expression, while significantly less frequent low expression (p < 0.05). GFAP+VEGF+dimMMP2-C5b-9+ rarely relapse, suggesting their utility a favorable relapse-free prognosis. recurrent GBMPs, positive correlation observed between GFAP+VEGF+bright MMP2+C5b-9+ MGMT gene promoter methylation (r 0.543, p Additionally, trend toward negative found MMP2+C5b-9- mutant p53 primary tissue -0.44, 0.114). These findings suggest that sEV profiles may serve valuable prognostic markers treatment responses.

Язык: Английский

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Dynamic Tumor in Situ Fluid Circulating Tumor DNA Postsurgery Effectively Predicts Recurrence and Clinical Benefits for Glioblastomas

Neurosurgery, Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

Glioblastoma (GBM) recurrence after surgery remains a significant clinical challenge because of limited early detection methods and effective molecular markers. This study investigates the potential dynamic tumor in situ fluid circulating DNA (TISF-ctDNA) as tool for monitoring residual disease evaluating treatment efficacy postsurgical patients with GBM. In this prospective cohort study, 75 resectable glioma were enrolled between October 2019 to June 2023. Primary tissues TISF samples collected, along cranial imaging. TISF-ctDNA was identified through targeted next-generation sequencing, positivity defined by presence one or more variants matching those primary tumors an increase ≥10 single-nucleotide across consecutive assessments. 62.2% period, indicating high prevalence disease. Patients positive showed significantly higher risk (hazard ratio 2.512, 95% CI 1.264-4.993, P = .0054). Conversion negativity post-treatment associated improved overall survival, highlighting its role response. Multivariate analysis revealed that independent predictor progression-free survival during adjuvant therapy, predictive accuracy (sensitivity 86.2%, specificity 100%). Importantly, preceded imaging signs median 71 days. no impact specific markers each subcohort (EGFR, TP53, PTEN, NF1) on observed. is promising biomarker GBM benefit. It provides insight into genomic evolution identifies who may benefit from chemotherapy. robust prognostic indicator patient outcomes marker frontline therapy.

Язык: Английский

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