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PLoS Biology May 2024Glioblastoma, the most aggressive and prevalent form of primary brain tumor, is characterized by rapid growth, diffuse infiltration, and resistance to therapies.... (Review)
Review
Glioblastoma, the most aggressive and prevalent form of primary brain tumor, is characterized by rapid growth, diffuse infiltration, and resistance to therapies. Intrinsic heterogeneity and cellular plasticity contribute to its rapid progression under therapy; therefore, there is a need to fully understand these tumors at a single-cell level. Over the past decade, single-cell transcriptomics has enabled the molecular characterization of individual cells within glioblastomas, providing previously unattainable insights into the genetic and molecular features that drive tumorigenesis, disease progression, and therapy resistance. However, despite advances in single-cell technologies, challenges such as high costs, complex data analysis and interpretation, and difficulties in translating findings into clinical practice persist. As single-cell technologies are developed further, more insights into the cellular and molecular heterogeneity of glioblastomas are expected, which will help guide the development of personalized and effective therapies, thereby improving prognosis and quality of life for patients.
Topics: Humans; Glioblastoma; Single-Cell Analysis; Brain Neoplasms; Transcriptome; Animals
PubMed: 38814900
DOI: 10.1371/journal.pbio.3002640 -
Frontiers in Neurology 2024Ultrasound waves were initially used as a diagnostic tool that provided critical insights into several pathological conditions (e.g., gallstones, ascites, pneumothorax,... (Review)
Review
Ultrasound waves were initially used as a diagnostic tool that provided critical insights into several pathological conditions (e.g., gallstones, ascites, pneumothorax, etc.) at the bedside. Over the past decade, advancements in technology have led to the use of ultrasound waves in treating many neurological conditions, such as essential tremor and Parkinson's disease, with high specificity. The convergence of ultrasound waves at a specific region of interest/target while avoiding surrounding tissue has led to the coined term "focused ultrasound (FUS)." In tumor research, ultrasound technology was initially used as an intraoperative guidance tool for tumor resection. However, in recent years, there has been growing interest in utilizing FUS as a therapeutic tool in the management of brain tumors such as gliomas. This mini-review highlights the current knowledge surrounding using FUS as a treatment modality for gliomas. Furthermore, we discuss the utility of FUS in enhanced drug delivery to the central nervous system (CNS) and highlight promising clinical trials that utilize FUS as a treatment modality for gliomas.
PubMed: 38813245
DOI: 10.3389/fneur.2024.1387986 -
Bioinformatics and Biology Insights 2024Glioma is currently one of the most prevalent types of primary brain cancer. Given its high level of heterogeneity along with the complex biological molecular markers,...
Glioma is currently one of the most prevalent types of primary brain cancer. Given its high level of heterogeneity along with the complex biological molecular markers, many efforts have been made to accurately classify the type of glioma in each patient, which, in turn, is critical to improve early diagnosis and increase survival. Nonetheless, as a result of the fast-growing technological advances in high-throughput sequencing and evolving molecular understanding of glioma biology, its classification has been recently subject to significant alterations. In this study, we integrate multiple glioma omics modalities (including mRNA, DNA methylation, and miRNA) from The Cancer Genome Atlas (TCGA), while using the revised glioma reclassified labels, with a supervised method based on sparse canonical correlation analysis (DIABLO) to discriminate between glioma types. We were able to find a set of highly correlated features distinguishing glioblastoma from lower-grade gliomas (LGGs) that were mainly associated with the disruption of receptor tyrosine kinases signaling pathways and extracellular matrix organization and remodeling. Concurrently, the discrimination of the LGG types was characterized primarily by features involved in ubiquitination and DNA transcription processes. Furthermore, we could identify several novel glioma biomarkers likely helpful in both diagnosis and prognosis of the patients, including the genes , and . Collectively, this comprehensive approach not only allowed a highly accurate discrimination of the different TCGA glioma patients but also presented a step forward in advancing our comprehension of the underlying molecular mechanisms driving glioma heterogeneity. Ultimately, our study also revealed novel candidate biomarkers that might constitute potential therapeutic targets, marking a significant stride toward personalized and more effective treatment strategies for patients with glioma.
PubMed: 38812741
DOI: 10.1177/11779322241249563 -
Journal of Integrative Neuroscience May 2024Multiple radiomics models have been proposed for grading glioma using different algorithms, features, and sequences of magnetic resonance imaging. The research seeks to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple radiomics models have been proposed for grading glioma using different algorithms, features, and sequences of magnetic resonance imaging. The research seeks to assess the present overall performance of radiomics for grading glioma.
METHODS
A systematic literature review of the databases Ovid MEDLINE PubMed, and Ovid EMBASE for publications published on radiomics for glioma grading between 2012 and 2023 was performed. The systematic review was carried out following the criteria of Preferred Reporting Items for Systematic Reviews and Meta-Analysis.
RESULTS
In the meta-analysis, a total of 7654 patients from 40 articles, were assessed. R-package mada was used for modeling the joint estimates of specificity (SPE) and sensitivity (SEN). Pooled event rates across studies were performed with a random-effects meta-analysis. The heterogeneity of SPE and SEN were based on the χ2 test. Overall values for SPE and SEN in the differentiation between high-grade gliomas (HGGs) and low-grade gliomas (LGGs) were 84% and 91%, respectively. With regards to the discrimination between World Health Organization (WHO) grade 4 and WHO grade 3, the overall SPE was 81% and the SEN was 89%. The modern non-linear classifiers showed a better trend, whereas textural features tend to be the best-performing (29%) and the most used.
CONCLUSIONS
Our findings confirm that present radiomics' diagnostic performance for glioma grading is superior in terms of SEN and SPE for the HGGs vs. LGGs discrimination task when compared to the WHO grade 4 vs. 3 task.
Topics: Glioma; Humans; Magnetic Resonance Imaging; Brain Neoplasms; Neoplasm Grading; Neuroimaging; Radiomics
PubMed: 38812383
DOI: 10.31083/j.jin2305100 -
Journal of Biomedical Research May 2024Glioblastoma multiforme (GBM) presents significant challenges in treatment, with current standard-of-care approaches offering limited efficacy and survival benefits....
Glioblastoma multiforme (GBM) presents significant challenges in treatment, with current standard-of-care approaches offering limited efficacy and survival benefits. This necessitates the development of innovative therapeutic strategies to enhance treatment outcomes. Nanotechnology has emerged as a promising avenue in cancer therapy, offering targeted drug delivery and enhanced therapeutic efficacy. Polymeric nanoparticles, particularly those based on Poly (lactic-co-glycolic acid) (PLGA), have gained traction as drug carriers due to their biocompatibility and controlled release properties. However, their interception by macrophages poses challenges to effective drug delivery. Superparamagnetic iron oxide (SPIO) nanoparticles have shown promise as radiosensitizers, enhancing the efficacy of radiotherapy through the generation of reactive oxygen species (ROS). Moreover, cell membrane biomimetic drug delivery systems have garnered attention for their ability to improve biocompatibility and targeting capabilities. Leveraging these concepts, our study introduces a novel multifunctional platform, GM@P (T/S), comprising polymeric nanoparticles coated with cancer cell membrane. By encapsulating temozolomide (TMZ) and SPIO nanoparticles within GM@P (T/S), we aim to synergistically enhance the cytotoxic effects of chemotherapy and radiotherapy against GBM while overcoming limitations associated with conventional treatments. This innovative approach holds promise for addressing the unmet clinical needs in GBM therapy and advancing towards more effective and personalized treatment strategies.
PubMed: 38812286
DOI: 10.7555/JBR.38.20240100 -
Scientific Reports May 2024Radiotherapy is the standard treatment for glioblastoma (GBM), but the overall survival rate for radiotherapy treated GBM patients is poor. The use of adjuvant and...
Radiotherapy is the standard treatment for glioblastoma (GBM), but the overall survival rate for radiotherapy treated GBM patients is poor. The use of adjuvant and concomitant temozolomide (TMZ) improves the outcome; however, the effectiveness of this treatment varies according to MGMT levels. Herein, we evaluated whether MGMT expression affected the radioresponse of human GBM, GBM stem-like cells (GSCs), and melanoma. Our results indicated a correlation between MGMT promoter methylation status and MGMT expression. MGMT-producing cell lines ACPK1, GBMJ1, A375, and MM415 displayed enhanced radiosensitivity when MGMT was silenced using siRNA or when inhibited by lomeguatrib, whereas the OSU61, NSC11, WM852, and WM266-4 cell lines, which do not normally produce MGMT, displayed reduced radiosensitivity when MGMT was overexpressed. Mechanistically lomeguatrib prolonged radiation-induced γH2AX retention in MGMT-producing cells without specific cell cycle changes, suggesting that lomeguatrib-induced radiosensitization in these cells is due to radiation-induced DNA double-stranded break (DSB) repair inhibition. The DNA-DSB repair inhibition resulted in cell death via mitotic catastrophe in MGMT-producing cells. Overall, our results demonstrate that MGMT expression regulates radioresponse in GBM, GSC, and melanoma, implying a role for MGMT as a target for radiosensitization.
Topics: Humans; Glioblastoma; Tumor Suppressor Proteins; DNA Repair Enzymes; Melanoma; DNA Modification Methylases; Cell Line, Tumor; Radiation Tolerance; Neoplastic Stem Cells; Promoter Regions, Genetic; DNA Methylation; DNA Repair; DNA Breaks, Double-Stranded; Gene Expression Regulation, Neoplastic; Temozolomide; Brain Neoplasms; Purines
PubMed: 38811596
DOI: 10.1038/s41598-024-61240-x -
PloS One 2024In the realm of Gut-Brain axis research, existing evidence points to a complex bidirectional regulatory mechanism between gut microbiota and the brain. However, the...
BACKGROUND
In the realm of Gut-Brain axis research, existing evidence points to a complex bidirectional regulatory mechanism between gut microbiota and the brain. However, the question of whether a causal relationship exists between gut microbiota and specific types of brain tumors, such as gliomas, remains unresolved. To address this gap, we employed publicly available Genome-Wide Association Study (GWAS) and MIOBEN databases, conducting an in-depth analysis using Two-Sample Mendelian Randomization (MR).
METHOD
We carried out two sets of MR analyses. The preliminary analysis included fewer instrumental variables due to a high genome-wide statistical significance threshold (5×10-8). To enable a more comprehensive and detailed analysis, we adjusted the significance threshold to 1×10-5. We performed linkage disequilibrium analysis (R2 <0.001, clumping distance = 10,000kb) and detailed screening of palindromic SNPs, followed by MR analysis and validation through sensitivity analysis.
RESULTS
Our findings reveal a causal relationship between gut microbiota and gliomas. Further confirmation via Inverse Variance Weighting (IVW) identified eight specific microbial communities related to gliomas. Notably, the Peptostreptococcaceae and Olsenella communities appear to have a protective effect, reducing glioma risk.
CONCLUSION
This study not only confirms the causal link between gut microbiota and gliomas but also suggests a new avenue for future glioma treatment.
Topics: Humans; Glioma; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Brain Neoplasms; Brain-Gut Axis; Linkage Disequilibrium
PubMed: 38809931
DOI: 10.1371/journal.pone.0304403 -
Journal of Cellular and Molecular... May 2024Glioma is a prevalent malignant tumour characterized by hypoxia as a pivotal factor in its progression. This study aims to investigate the impact of the most severely...
Glioma is a prevalent malignant tumour characterized by hypoxia as a pivotal factor in its progression. This study aims to investigate the impact of the most severely hypoxic cell subpopulation in glioma. Our findings reveal that the THBD macrophage subpopulation is closely associated with hypoxia in glioma, exhibiting significantly higher infiltration in tumours compared to non-tumour tissues. Moreover, a high proportion of THBD cells correlates with poor prognosis in glioblastoma (GBM) patients. Notably, THBD macrophages exhibit hypoxic characteristics and epithelial-mesenchymal transition features. Silencing THBD expression leads to a notable reduction in the proliferation and metastasis of glioma cells. Furthermore, we developed a THBD macrophage-related risk signature (THBDMRS) through machine learning techniques. THBDMRS emerges as an independent prognostic factor for GBM patients with a substantial prognostic impact. By comparing THBDMRS with 119 established prognostic features, we demonstrate the superior prognostic performance of THBDMRS. Additionally, THBDMRS is associated with glioma metastasis and extracellular matrix remodelling. In conclusion, hypoxia-related THBD macrophages play a pivotal role in glioma pathogenesis, and THBDMRS emerges as a potent and promising prognostic tool for GBM, contributing to enhanced patient survival outcomes.
Topics: Humans; Macrophages; Prognosis; Glioma; Brain Neoplasms; Epithelial-Mesenchymal Transition; Tumor Microenvironment; Cell Proliferation; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Hypoxia; Biomarkers, Tumor; Risk Factors; Cell Hypoxia; Male; Female
PubMed: 38809929
DOI: 10.1111/jcmm.18393 -
Asian Pacific Journal of Cancer... May 2024Glioblastoma Multiforme (GBM) poses a significant challenge due to its high aggressiveness and unfavorable prognosis, with existing treatments demonstrating limited...
OBJECTIVE
Glioblastoma Multiforme (GBM) poses a significant challenge due to its high aggressiveness and unfavorable prognosis, with existing treatments demonstrating limited efficacy in prolonging survival rates. This study aimed to assess the anticancer properties of Aaptos suberitoides extracts and fraction on the U87 cell line, serving as a representative model for GBM.
METHODS
U87 cells were treated with ethanol extracts derived from Aaptos suberitoides, specifically two extracts (OAA-1 and OAA-2) and one ethyl acetate fraction (EA) isolated from specimens collected on Pramuka Island and Tinjil Island. The evaluation encompased microscopic observation and MTT assay to determine the IC50. Subsequently, antiproliferative effects were investigated through apoptosis and cell cycle assays.
RESULTS
The extract demonstrated cytotoxic activity against U87 cells, with OAA-1 and OAA-2 exhibiting IC50 values of 35.78 μg/mL and 25.38 μg/mL, respectively. OAA-1 notably induced apoptosis at 50 μg/mL and induced cell cycle arrest. On other hand, OAA-2, while also inducing apoptosis significantly, had a lesser impact on cell cycle arrest. In contrast, EA induced significant apoptosis at a concentration of 100 μg/mL.
CONCLUSION
The ethanol extracts and the ethyl acetate fraction of Aaptos suberitoides emerged as a promising candidate for Glioblastoma Multiforme cancer therapy, showing potential in inhibiting cell proliferation and inducing apoptosis.
Topics: Humans; Glioblastoma; Apoptosis; Cell Proliferation; Plant Extracts; Tumor Cells, Cultured; Cell Cycle; Cell Cycle Checkpoints; Cell Line, Tumor; Brain Neoplasms
PubMed: 38809654
DOI: 10.31557/APJCP.2024.25.5.1815 -
Oncology Letters Jul 2024Gliomas are highly malignant and invasive tumors lacking clear boundaries. Previous bioinformatics and experimental analyses have indicated that F-box and leucine-rich...
Gliomas are highly malignant and invasive tumors lacking clear boundaries. Previous bioinformatics and experimental analyses have indicated that F-box and leucine-rich repeat protein 6 (FBXL6), a protein crucial for the cell cycle and tumorigenesis, is highly expressed in certain types of tumors. The high expression level of FBXL6 is reported to promote tumor growth and adversely affect patient survival. However, the molecular mechanism, prognostic value and drug sensitivity of FBXL6 in glioma remain unclear. To address this, the present study analyzed FBXL6 expression in gliomas, utilizing data from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. Analysis of FBXL6 mRNA expression levels, combined with patient factors such as age, sex and tumor grade using Kaplan-Meier plots and nomograms, demonstrated a strong correlation between FBXL6 expression and glioma progression. Co-expression networks provided further insights into the biological function of FBXL6. Additionally, using CIBERSORT and TISDB tools, the correlation between FBXL6 expression correlation tumor-infiltrating immune cells and immune genes was demonstrated to be statistically significant. These findings were validated by examining FBXL6 mRNA and protein levels in glioma tissues using various techniques, including western blot, reverse transcription-quantitative PCR and immunohistochemistry. These assays demonstrated the role of FBXL6 in glioma progression. Furthermore, drug sensitivity analysis demonstrated a strong correlation between FBXL6 expression and various drugs, which indicated that FBXL6 may potentially act as a future promising therapeutic target in glioma treatment. Therefore, the present study identified FBXL6 as a diagnostic and prognostic marker in patients with gliomas and highlighted its potential role in glioma progression.
PubMed: 38807668
DOI: 10.3892/ol.2024.14453