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Clinical and Translational Medicine Feb 2024Paediatric and adult astrocytomas are notably different, where clinical treatments used for adults are not as effective on children with the same form of cancer and... (Review)
Review
Paediatric and adult astrocytomas are notably different, where clinical treatments used for adults are not as effective on children with the same form of cancer and these treatments lead to adverse long-term health concerns. Integrative omics-based studies have shown the pathology and fundamental molecular characteristics differ significantly and cannot be extrapolated from the more widely studied adult disease. Recent clinical advances in our understanding of paediatric astrocytomas, with the aid of next-generation sequencing and epigenome-wide profiling, have led to the identification of key canonical mutations that vary based on the tumour location and age of onset. These driver mutations, in particular the identification of the recurrent histone H3 mutations in high-grade tumours, have confirmed the important role epigenetic dysregulations play in cancer progression. This review summarises the current updates of the classification, epidemiology, pathogenesis and clinical management of paediatric astrocytoma based on their grades and the ongoing clinical trials. It also provides novel insights on genetic and epigenetic alterations as diagnostic biomarkers, highlighting the potential of targeting these pathways as therapeutics for this devastating childhood cancer.
Topics: Adult; Humans; Child; Brain Neoplasms; Astrocytoma; Histones; Epigenesis, Genetic; Epigenomics
PubMed: 38299304
DOI: 10.1002/ctm2.1560 -
Nature Cancer Sep 2023
Topics: Humans; Glioblastoma; Myeloid Cells; Antigens, CD; Sialic Acid Binding Immunoglobulin-like Lectins
PubMed: 37500790
DOI: 10.1038/s43018-023-00603-1 -
Current Opinion in Cell Biology Dec 2023Glioblastoma is the most common and aggressive primary brain tumor, characterized by a highly complex and heterogeneous tumor immune microenvironment (TIME). In this... (Review)
Review
Glioblastoma is the most common and aggressive primary brain tumor, characterized by a highly complex and heterogeneous tumor immune microenvironment (TIME). In this review, we discuss the impact of tumor-intrinsic and tumor-extrinsic drivers that contribute to heterogeneity in the adult glioblastoma TIME, focusing on four main factors: genetic drivers, sex, age, and standard of care therapy. We describe recent insights into how each of these factors affects key aspects ranging from TIME composition to therapy response, with an emphasis on the cross-talk between tumor and immune cells. Deciphering these local interactions is fundamental to understanding therapy resistance and identifying novel immunomodulatory strategies.
Topics: Adult; Humans; Glioblastoma; Brain Neoplasms; Tumor Microenvironment
PubMed: 37984008
DOI: 10.1016/j.ceb.2023.102279 -
Therapeutic Hypothermia and Temperature... Mar 2024Glioblastoma (GBM) is the most commonly occurring of all malignant central nervous system (CNS) tumors in adults. Considering the low median survival of only ∼15... (Review)
Review
Glioblastoma (GBM) is the most commonly occurring of all malignant central nervous system (CNS) tumors in adults. Considering the low median survival of only ∼15 months and poor prognosis in GBM patients, despite surgical resection with adjuvant radiation and chemotherapy, it is vital to seek brand new and innovative treatment in combination with already existing methods. Hypothermia participates in many metabolic pathways, inflammatory responses, and apoptotic processes, while also promoting the integrity of neurons. Following the successful application of therapeutic hypothermia across a spectrum of disorders such as traumatic CNS injury, cardiac arrest, and epilepsy, several clinical trials have set to evaluate the potency of hypothermia in treating a variety of cancers, including breast and ovaries cancer. In regard to primary neoplasms and more specifically, GBM, hypothermia has recently shown promising results as an auxiliary treatment, reinforcing chemotherapy's efficacy. In this review, we discuss the recent advances in utilizing hypothermia as treatment for GBM and other cancers.
Topics: Adult; Humans; Glioblastoma; Hypothermia; Brain Neoplasms; Hypothermia, Induced; Combined Modality Therapy
PubMed: 37184912
DOI: 10.1089/ther.2023.0014 -
Clinica Chimica Acta; International... Mar 2024Glioblastoma (GBM) is the most common type of malignant brain tumor.The discovery of microRNAs and their unique properties have made them suitable tools as biomarkers... (Review)
Review
Glioblastoma (GBM) is the most common type of malignant brain tumor.The discovery of microRNAs and their unique properties have made them suitable tools as biomarkers for cancer diagnosis, prognosis, and evaluation of therapeutic response using different types of nanomaterials as sensitive and specific biosensors. In this review, we discuss microRNA-based electrochemical biosensing systems and the use of nanoparticles in the evolving development of microRNA-based biosensors in glioblastoma.
Topics: Humans; MicroRNAs; Glioblastoma; Nanostructures; Nanoparticles; Biomarkers, Tumor; Biosensing Techniques; Electrochemical Techniques
PubMed: 38355000
DOI: 10.1016/j.cca.2024.117829 -
Journal of Translational Medicine Nov 2023To develop and validate a conventional MRI-based radiomic model for predicting prognosis in patients with IDH wild-type glioblastoma (GBM) and reveal the biological...
BACKGROUND
To develop and validate a conventional MRI-based radiomic model for predicting prognosis in patients with IDH wild-type glioblastoma (GBM) and reveal the biological underpinning of the radiomic phenotypes.
METHODS
A total of 801 adult patients (training set, N = 471; internal validation set, N = 239; external validation set, N = 91) diagnosed with IDH wild-type GBM were included. A 20-feature radiomic risk score (Radscore) was built for overall survival (OS) prediction by univariate prognostic analysis and least absolute shrinkage and selection operator (LASSO) Cox regression in the training set. GSEA and WGCNA were applied to identify the intersectional pathways underlying the prognostic radiomic features in a radiogenomic analysis set with paired MRI and RNA-seq data (N = 132). The biological meaning of the conventional MRI sequences was revealed using a Mantel test.
RESULTS
Radscore was demonstrated to be an independent prognostic factor (P < 0.001). Incorporating the Radscore into a clinical model resulted in a radiomic-clinical nomogram predicting survival better than either the Radscore model or the clinical model alone, with better calibration and classification accuracy (a total net reclassification improvement of 0.403, P < 0.001). Three pathway categories (proliferation, DNA damage response, and immune response) were significantly correlated with the prognostic radiomic phenotypes.
CONCLUSION
Our findings indicated that the prognostic radiomic phenotypes derived from conventional MRI are driven by distinct pathways involved in proliferation, DNA damage response, and immunity of IDH wild-type GBM.
Topics: Adult; Humans; Glioblastoma; Brain Neoplasms; Retrospective Studies; Magnetic Resonance Imaging; Risk Assessment
PubMed: 37993907
DOI: 10.1186/s12967-023-04551-3 -
Child's Nervous System : ChNS :... Jun 2024The World Health Organization's 5th edition classification of Central Nervous System (CNS) tumors differentiates diffuse gliomas into adult and pediatric variants....
The World Health Organization's 5th edition classification of Central Nervous System (CNS) tumors differentiates diffuse gliomas into adult and pediatric variants. Pediatric-type diffuse low-grade gliomas (pDLGGs) are distinct from adult gliomas in their molecular characteristics, biological behavior, clinical progression, and prognosis. Various molecular alterations identified in pDLGGs are crucial for treatment. There are four distinct entities of pDLGGs. All four of these tumor subtypes exhibit diffuse growth and share overlapping histopathological and imaging characteristics. Molecular analysis is essential for differentiating these lesions.
PubMed: 38926169
DOI: 10.1007/s00381-024-06500-x -
Astrocytoma and glioblastoma IDH1-wildtype cells colonize tumor vessels and deploy vascular mimicry.Ultrastructural Pathology Jul 2023Gliomas are the most prevalent type of malignant brain tumors with a very dismal prognosis. Angiogenesis in glioma has recently gotten more attention and its molecular...
Gliomas are the most prevalent type of malignant brain tumors with a very dismal prognosis. Angiogenesis in glioma has recently gotten more attention and its molecular aspects have been published; however, these were not complemented with ultrastructural evidence. Our ultrastructural examination of glioma vessels reveals several unique and critical features related to their mechanisms of progression and metastasis strategy. The detailed ultrastructural survey of 18 isocitrate dehydrogenase-wildtype (IDH1-wt) glioblastomas and 12 isocitrate dehydrogenase-mutant (IDH1-mt) High-grade gliomas indicated that tumor vessels of both types had undergone deformities such as the thickening of the vessel wall (VW) and proliferation of the basement membrane, contour distortions, abnormal and discontinuous basal lamina, tumor cells' invasion and colonization of VW, disappearance of endothelial cells (ECs), pericytes, and smooth muscle cells, as well as the formation of a continuous ring of tumor cells attached to the luminal side of VW in numerous cases. The latter feature is a clear sign of vascular mimicry (VM) that was previously suggested in gliomas but never shown by TEM. Additionally, the vascular invasion was carried out by a large number of tumor cells and was accompanied by the accumulation of tumor lipids in the vessels' lumina and VWs; these two features are distinct for gliomas and may alter the course of the clinical presentation and overall prognosis. This raises the issue of how to specifically target tumor cells involved in vascular invasion in order to optimize prognosis and overcome these mechanisms employed by the tumor cells.
Topics: Humans; Glioblastoma; Isocitrate Dehydrogenase; Endothelial Cells; Astrocytoma; Glioma; Brain Neoplasms; Mutation
PubMed: 37144386
DOI: 10.1080/01913123.2023.2205927 -
Cells Sep 2023Brain tumors represent a heterogeneous group of neoplasms involving the brain or nearby tissues, affecting populations of all ages with a high incidence worldwide. Among... (Review)
Review
Brain tumors represent a heterogeneous group of neoplasms involving the brain or nearby tissues, affecting populations of all ages with a high incidence worldwide. Among the primary brain tumors, the most aggressive and also the most common is glioblastoma (GB), a type of glioma that falls into the category of IV-grade astrocytoma. GB often leads to death within a few months after diagnosis, even if the patient is treated with available therapies; for this reason, it is important to continue to discover new therapeutic approaches to allow for a better survival rate of these patients. Immunotherapy, today, seems to be one of the most innovative types of treatment, based on the ability of the immune system to counteract various pathologies, including cancer. In this context, interleukin 21 (IL-21), a type I cytokine produced by natural killer (NK) cells and CD4 T lymphocytes, appears to be a valid target for new therapies since this cytokine is involved in the activation of innate and adaptive immunity. To match this purpose, our review deeply evaluated how IL-21 could influence the progression of GB, analyzing its main biological processes and mechanisms while evaluating the potential use of the latest available therapies.
Topics: Humans; Glioblastoma; Interleukins; Cytokines; Glioma
PubMed: 37759505
DOI: 10.3390/cells12182284 -
Metabolic Brain Disease Aug 2023Glioblastoma Multiforme (GBM) is the primary brain tumor and accounts for 200,000 deaths each year worldwide. The standard therapy includes surgical resection followed... (Review)
Review
Glioblastoma Multiforme (GBM) is the primary brain tumor and accounts for 200,000 deaths each year worldwide. The standard therapy includes surgical resection followed by temozolomide (TMZ)-based chemotherapy and radiotherapy. The survival period of GBM patients is only 12-15 months. Therefore, novel treatment modalities for GBM treatment are urgently needed. Mounting evidence reveals that non-coding RNAs (ncRNAs) were involved in regulating gene expression, the pathophysiology of GBM, and enhancing therapeutic outcomes. The combinatory use of ncRNAs, chemotherapeutic drugs, and tumor suppressor gene expression induction might provide an innovative, alternative therapeutic approach for managing GBM. Studies have highlighted the role of Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in prognosis and diagnosis. Dysregulation of ncRNAs is observed in virtually all tumor types, including GBMs. Studies have also indicated the blood-brain barrier (BBB) as a crucial factor that hinders chemotherapy. Although several nanoparticle-mediated drug deliveries were degrading effectively against GBM in vitro conditions. However, the potential to cross the BBB and optimum delivery of oligonucleotide RNA into GBM cells in the brain is currently under intense clinical trials. Despite several advances in molecular pathogenesis, GBM remains resistant to chemo and radiotherapy. Targeted therapies have less clinical benefit due to high genetic heterogeneity and activation of alternative pathways. Thus, identifying GBM-specific prognostic pathways, essential genes, and genomic aberrations provide several potential benefits as subtypes of GBM. Also, these approaches will provide insights into new strategies to overcome the heterogenous nature of GBM, which will eventually lead to successful therapeutic interventions toward precision medicine and precision oncology.
Topics: Humans; Glioblastoma; Prognosis; Precision Medicine; Temozolomide; MicroRNAs; Brain Neoplasms; Cell Line, Tumor
PubMed: 37249862
DOI: 10.1007/s11011-023-01234-2