Macrophages and microglia in glioblastoma: heterogeneity, plasticity, and therapy

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(1)

Published: Jan. 2, 2023

Glioblastoma (GBM) is the most aggressive tumor in central nervous system and contains a highly immunosuppressive microenvironment (TME). Tumor-associated macrophages microglia (TAMs) are dominant population of immune cells GBM TME that contribute to hallmarks, including immunosuppression. The understanding TAMs has been limited by lack powerful tools characterize them. However, recent progress on single-cell technologies offers an opportunity precisely at level identify new TAM subpopulations with specific tumor-modulatory functions GBM. In this Review, we discuss heterogeneity plasticity summarize current TAM-targeted therapeutic potential We anticipate use followed functional studies will accelerate development novel effective therapeutics for patients.

Language: Английский

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lncRNA Biomarkers of Glioblastoma Multiforme

Biomedicines, Journal Year: 2024, Volume and Issue: 12(5), P. 932 - 932

Published: April 23, 2024

Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that not translated into proteins. Their expression is tissue-specific, with the vast majority involved regulation cellular processes and functions. Many human diseases, including cancer, have been shown to be associated deregulated lncRNAs, rendering them potential therapeutic targets biomarkers for differential diagnosis. The lncRNAs nervous system varies different cell types, implicated mechanisms neurons glia, effects on development functioning brain. Reports also a link between changes lncRNA etiopathogenesis brain neoplasia, glioblastoma multiforme (GBM). GBM an aggressive variant cancer unfavourable prognosis median survival 14-16 months. It considered brain-specific disease highly invasive malignant cells spreading throughout neural tissue, impeding complete resection, leading post-surgery recurrences, which prime cause mortality. early diagnosis could improve treatment extend survival, profiling biological fluids promising detection neoplastic at their initial stages effective interventions. This review presents systematic overview GBM-associated deregulation focus fingerprints patients' blood.

Language: Английский

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Histological and molecular glioblastoma, IDH-wildtype: a real-world landscape using the 2021 WHO classification of central nervous system tumors

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: July 6, 2023

Glioblastoma (GBM), the most lethal primary brain malignancy, is divided into histological (hist-GBM) and molecular (mol-GBM) subtypes according to 2021 World Health Organization classification of central nervous system tumors. This study aimed characterize clinical, radiological, molecular, survival features GBM under current scheme explore determinants.We re-examined genetic alterations IDH-wildtype diffuse gliomas at our institute from 2011 2022, enrolled GBMs for analysis after re-classification. Univariable multivariable analyses were used identify determinants.Among 209 gliomas, 191 GBMs, including 146 hist-GBMs (76%) 45 mol-GBMs (24%). Patients with younger, less likely develop preoperative motor dysfunction, more epilepsy than hist-GBMs. Mol-GBMs exhibited lower radiographic incidences contrast enhancement intratumoral necrosis. Common included copy-number changes in chromosomes 1, 7, 9, 10, 19, as well EGFR, TERT, CDKN2A/B, PTEN, distinct patterns observed between two subtypes. The median overall (mOS) GMB was 12.6 months. had a higher mOS hist-GBMs, although not statistically significant (15.6 vs. 11.4 months, p=0.17). Older age, male sex, tumor involvement deep structure or functional area, CDK4, CDK6, CIC, FGFR3, KMT5B, MYB predictors worse prognosis, while MGMT promoter methylation, maximal resection, treatment based on Stupp protocol predictive better survival.The definition its prognostic characteristics have been altered classification.

Language: Английский

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Molecular GBM versus Histopathological GBM: Radiology-Pathology-Genetic Correlation and the New WHO 2021 Definition of Glioblastoma

American Journal of Neuroradiology, Journal Year: 2024, Volume and Issue: 45(8), P. 1006 - 1012

Published: March 4, 2024

ABSTRACT

Given the recent advances in molecular pathogenesis of tumors, with better correlation tumor behavior and prognosis, major changes were made to new 2021 WHO (CNS5) classification CNS including updated criteria for diagnosis glioblastoma. Diagnosis GBM now requires absence isocitrate dehydrogenase histone 3 mutations (IDH-wildtype H3-wildtype) as basic cornerstone, elimination IDH-mutated category. The requirements conventionally histopathological, based on presence pathognomonic features such microvascular proliferation necrosis. However, even if these histological are absent, many lower grade (WHO 2/3) diffuse astrocytic gliomas behave clinically similar (grade 4). introduced that can be used upgrade histologically lower-grade, IDH-wildtype, astrocytomas GBM. three include: concurrent gain whole chromosome 7 loss 10 (+7/-10); TERT promoter mutation; epidermal growth factor receptor (EGFR) amplification. changes, it is strongly recommended have analysis 2/3 astrocytic, adult patients, identification any above allows upgrading 4 ("molecular GBM") important prognostic implications. Despite at an early stage, there active ongoing research unique MRI This paper highlights differences between "molecular" "histopathological" GBM, aim providing a understanding about changes. ABBREVIATIONS: GBM=Glioblastoma; TERT=telomerase reverse transcriptase; EGFR=epidermal receptor; MGMT= methylguanine-DNA methyltransferase; NGS= next-generation sequencing; IDH=

Language: Английский

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Radiogenomics and machine learning predict oncogenic signaling pathways in glioblastoma

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 27, 2025

Language: Английский

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Glycosylation spectral signatures for glioma grade discrimination using Raman spectroscopy

BMC Cancer, Journal Year: 2023, Volume and Issue: 23(1)

Published: Feb. 21, 2023

Gliomas are the most common brain tumours with high-grade glioblastoma representing aggressive and lethal form. Currently, there is a lack of specific glioma biomarkers that would aid tumour subtyping minimally invasive early diagnosis. Aberrant glycosylation an important post-translational modification in cancer implicated progression. Raman spectroscopy (RS), vibrational spectroscopic label-free technique, has already shown promise diagnostics.RS was combined machine learning to discriminate grades. spectral signatures patterns were used serum samples fixed tissue biopsy samples, as well single cells spheroids.Glioma grades patient discriminated high accuracy. Discrimination between higher malignant (III IV) achieved accuracy tissue, serum, cellular models using spheroids. Biomolecular changes assigned alterations corroborated by analysing glycan standards other such carotenoid antioxidant content.RS could pave way for more objective less grading patients, serving useful tool facilitate diagnosis delineate biomolecular progression changes.

Language: Английский

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The Bioinformatics Identification of Potential Protein Glycosylation Genes Associated with a Glioma Stem Cell Signature

BioMedInformatics, Journal Year: 2024, Volume and Issue: 4(1), P. 75 - 88

Published: Jan. 1, 2024

Glioma stem cells (GSCs) contribute to the pathogenesis of glioblastoma (GBM), which is most malignant form glioma. The implications and underlying mechanisms protein glycosylation in GSC phenotypes GBM malignancy are not fully understood. implication corresponding candidate genes on cell properties GSCs poor clinical outcomes were investigated, using datasets from Gene Expression Omnibus, Cancer Genome Atlas, Chinese accompanied by biological validation vitro. N-linked was significantly associated with prognosis integrated bioinformatics analyses specimens. glioma grade, molecular biomarkers, subtypes. expression levels asparagine-linked (ALG) enzyme family, essential for early steps biosynthesis N-glycans, prominently survival patients high stem-cell properties. Finally, oxidative phosphorylation pathway primarily enriched a ALG family. These findings suggest role regulation malignancy.

Language: Английский

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Cannabinoids in the treatment of glioblastoma

Pharmacological Reports, Journal Year: 2024, Volume and Issue: 76(2), P. 223 - 234

Published: March 8, 2024

Language: Английский

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Updates on management of gliomas in the molecular age

World Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 15(2), P. 178 - 194

Published: Feb. 19, 2024

Gliomas are primary brain tumors derived from glial cells of the central nervous system, afflicting both adults and children with distinct characteristics therapeutic challenges. Recent developments have ushered in novel clinical molecular prognostic factors, reshaping treatment paradigms based on classification grading, determined by histological attributes cellular lineage. This review article delves into diverse modalities tailored to specific grades classifications gliomas that currently being discussed used clinically year 2023. For adults, triad typically consists surgical resection, chemotherapy, radiotherapy. In contrast, pediatric gliomas, due their diversity, require a more approach. Although complete tumor excision can be curative location grade glioma, certain non-resectable cases demand chemotherapy approach usually involving, vincristine carboplatin. Additionally, if surgery or strategies unsuccessful, Vinblastine used. Despite recent advancements methodologies, there remains need exploration literature, particularly concerning efficacy regimens for isocitrate dehydrogenase type mutant astrocytomas fine-tuned approaches cohorts. explores employed adult context classification.

Language: Английский

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Case report: A rare case of a long-term survivor of glioblastoma who underwent two courses of hypofractionated radiotherapy as part of her care

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 4, 2025

Glioblastoma (GB) is a primary brain tumor that lethal and challenging to treat. The 3-year overall survival (OS) of patients with this diagnosis has stayed the same since 2005. patient 75-year-old woman who presented progressive aphasia was diagnosed GB (WHO grade 4, IDH1/IDH2 wild type, ATRX intact, p53 PTEN mutant, BRAF non-mutated, O 6 -methylguanine-DNA methyltransferase promoter methylated) underwent surgical resection, hypofractionated radiotherapy (HFRT) using intensity-modulated (IMRT) (4,005 cGy in 15 fractions) alone, adjuvant temozolomide (TMZ). She progression-free for approximately 20 months. Although planned, concurrent TMZ not used during complete first course HFRT due patient’s performance status. After recurrence, another (35 Gy 10 employed. on imaging 8 months until recent follow-up scan showed potential progression versus radiation-related change. At time case report, her care still ongoing. This represents rare long-term survivor received two courses HFRT, treatment option usually those predicted shorter times.

Language: Английский

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