RESUMEN
Postoperative radiotherapy remains the gold standard for malignant glioma treatment. Clinical limitations, including tumor growth between surgery and radiotherapy and the emergence of radioresistance, reduce treatment effectiveness and result in local disease progression. This study aimed to develop a local drug delivery system to inhibit tumor growth before radiotherapy and enhance the subsequent anticancer effects of limited-dose radiotherapy. We developed a compound of carboplatin-loaded hydrogel (CPH) incorporated with carboplatin-loaded calcium carbonate (CPCC) to enable two-stage (peritumoral and intracellular) release of carboplatin to initially inhibit tumor growth and to synergize with limited-dose radiation (10 Gy in a single fraction) to eliminate malignant glioma (ALTS1C1 cells) in a C57BL/6 mouse subcutaneous tumor model. The doses of carboplatin in CPH and CPCC treatments were 150 µL (carboplatin concentration of 5 mg/mL) and 15 mg (carboplatin concentration of 4.1 µg/mg), respectively. Mice receiving the combination of CPH-CPCC treatment and limited-dose radiation exhibited significantly reduced tumor growth volume compared to those receiving double-dose radiation alone. Furthermore, combining CPH-CPCC treatment with limited-dose radiation resulted in significantly longer progression-free survival than combining CPH treatment with limited-dose radiation. Local CPH-CPCC delivery synergized effectively with limited-dose radiation to eliminate mouse glioma, offering a promising solution for overcoming clinical limitations.
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Carbonato de Calcio , Carboplatino , Glioma , Hidrogeles , Ratones Endogámicos C57BL , Animales , Glioma/patología , Glioma/tratamiento farmacológico , Glioma/radioterapia , Carboplatino/administración & dosificación , Carboplatino/uso terapéutico , Carboplatino/farmacología , Hidrogeles/química , Línea Celular Tumoral , Carbonato de Calcio/química , Ratones , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/radioterapiaRESUMEN
Significance: ALA-PpIX and second-window indocyanine green (ICG) have been studied widely for guiding the resection of high-grade gliomas. These agents have different mechanisms of action and uptake characteristics, which can affect their performance as surgical guidance agents. Elucidating these differences in animal models that approach the size and anatomy of the human brain would help guide the use of these agents. Herein, we report on the use of a new pig glioma model and fluorescence cryotomography to evaluate the 3D distributions of both agents throughout the whole brain. Aim: We aim to assess and compare the 3D spatial distributions of ALA-PpIX and second-window ICG in a glioma-bearing pig brain using fluorescence cryotomography. Approach: A glioma was induced in the brain of a transgenic Oncopig via adeno-associated virus delivery of Cre-recombinase plasmids. After tumor induction, the pro-drug 5-ALA and ICG were administered to the animal 3 and 24 h prior to brain harvest, respectively. The harvested brain was imaged using fluorescence cryotomography. The fluorescence distributions of both agents were evaluated in 3D in the whole brain using various spatial distribution and contrast performance metrics. Results: Significant differences in the spatial distributions of both agents were observed. Indocyanine green accumulated within the tumor core, whereas ALA-PpIX appeared more toward the tumor periphery. Both ALA-PpIX and second-window ICG provided elevated tumor-to-background contrast (13 and 23, respectively). Conclusions: This study is the first to demonstrate the use of a new glioma model and large-specimen fluorescence cryotomography to evaluate and compare imaging agent distribution at high resolution in 3D.
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Neoplasias Encefálicas , Glioma , Imagenología Tridimensional , Verde de Indocianina , Animales , Verde de Indocianina/farmacocinética , Verde de Indocianina/química , Porcinos , Neoplasias Encefálicas/diagnóstico por imagen , Glioma/diagnóstico por imagen , Glioma/patología , Imagenología Tridimensional/métodos , Ácido Aminolevulínico/farmacocinética , Encéfalo/diagnóstico por imagen , Imagen Óptica/métodos , Modelos Animales de EnfermedadRESUMEN
The systematic review and meta-analysis titled "The Effects of Dabrafenib and/or Trametinib Treatment in BRAF V600-Mutant Glioma" provides a critical evaluation of these targeted therapies for a challenging subset of gliomas. This review is notable for its comprehensive data integration, offering a robust assessment of the efficacy and safety of dabrafenib and trametinib. By focusing on BRAF V600 mutations, it contributes valuable insights into personalized treatment strategies. However, limitations include study heterogeneity and a lack of long-term follow-up data, which hinder the generalizability and complete understanding of treatment effects. Additionally, while the review emphasizes therapeutic potential, it requires a thorough evaluation of adverse effects. Future research should address these limitations by providing more consistent data, longer follow-up, and a balanced view of treatment risks and benefits.
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Neoplasias Encefálicas , Glioma , Imidazoles , Mutación , Oximas , Proteínas Proto-Oncogénicas B-raf , Piridonas , Pirimidinonas , Humanos , Oximas/uso terapéutico , Pirimidinonas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/genética , Piridonas/uso terapéutico , Glioma/tratamiento farmacológico , Glioma/genética , Imidazoles/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genéticaRESUMEN
Brain tumors pose significant global health concerns due to their high mortality rates and limited treatment options. These tumors, arising from abnormal cell growth within the brain, exhibits various sizes and shapes, making their manual detection from magnetic resonance imaging (MRI) scans a subjective and challenging task for healthcare professionals, hence necessitating automated solutions. This study investigates the potential of deep learning, specifically the DenseNet architecture, to automate brain tumor classification, aiming to enhance accuracy and generalizability for clinical applications. We utilized the Figshare brain tumor dataset, comprising 3,064 T1-weighted contrast-enhanced MRI images from 233 patients with three prevalent tumor types: meningioma, glioma, and pituitary tumor. Four pre-trained deep learning models-ResNet, EfficientNet, MobileNet, and DenseNet-were evaluated using transfer learning from ImageNet. DenseNet achieved the highest test set accuracy of 96%, outperforming ResNet (91%), EfficientNet (91%), and MobileNet (93%). Therefore, we focused on improving the performance of the DenseNet, while considering it as base model. To enhance the generalizability of the base DenseNet model, we implemented a fine-tuning approach with regularization techniques, including data augmentation, dropout, batch normalization, and global average pooling, coupled with hyperparameter optimization. This enhanced DenseNet model achieved an accuracy of 97.1%. Our findings demonstrate the effectiveness of DenseNet with transfer learning and fine-tuning for brain tumor classification, highlighting its potential to improve diagnostic accuracy and reliability in clinical settings.
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Neoplasias Encefálicas , Aprendizaje Profundo , Imagen por Resonancia Magnética , Humanos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/clasificación , Imagen por Resonancia Magnética/métodos , Meningioma/diagnóstico por imagen , Meningioma/patología , Glioma/diagnóstico por imagen , Glioma/patología , Glioma/clasificación , Masculino , Femenino , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/clasificaciónRESUMEN
Histone H3-mutant gliomas are deadly brain tumors characterized by a dysregulated epigenome and stalled differentiation. In contrast to the extensive datasets available on tumor cells, limited information exists on their tumor microenvironment (TME), particularly the immune infiltrate. Here, we characterize the immune TME of H3.3K27M and G34R/V-mutant gliomas, and multiple H3.3K27M mouse models, using transcriptomic, proteomic and spatial single-cell approaches. Resolution of immune lineages indicates high infiltration of H3-mutant gliomas with diverse myeloid populations, high-level expression of immune checkpoint markers, and scarce lymphoid cells, findings uniformly reproduced in all H3.3K27M mouse models tested. We show these myeloid populations communicate with H3-mutant cells, mediating immunosuppression and sustaining tumor formation and maintenance. Dual inhibition of myeloid cells and immune checkpoint pathways show significant therapeutic benefits in pre-clinical syngeneic mouse models. Our findings provide a valuable characterization of the TME of oncohistone-mutant gliomas, and insight into the means for modulating the myeloid infiltrate for the benefit of patients.
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Neoplasias Encefálicas , Glioma , Histonas , Mutación , Células Mieloides , Microambiente Tumoral , Animales , Glioma/genética , Glioma/inmunología , Glioma/patología , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Células Mieloides/metabolismo , Células Mieloides/inmunología , Histonas/metabolismo , Histonas/genética , Ratones , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/patología , Humanos , Línea Celular Tumoral , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Regulación Neoplásica de la Expresión Génica , Análisis de la Célula IndividualRESUMEN
Gliomas are highly complex and metabolically active brain tumors associated with poor prognosis. Recent reports have found altered levels of blood metabolites during early tumor development, suggesting that tumor development could be detected several years before clinical manifestation. In this study, we performed metabolite analyses of blood samples collected from healthy controls and future glioma patients, up to eight years before glioma diagnosis, and on the day of glioma surgery. We discovered that metabolites related to early glioma development were associated with an increased energy turnover, as highlighted by elevated levels of TCA-related metabolites such as fumarate, malate, lactate and pyruvate in pre-diagnostic cases. We also found that metabolites related to glioma progression at surgery were primarily high levels of amino acids and metabolites of amino acid catabolism, with elevated levels of 11 amino acids and two branched-chain alpha-ketoacids, ketoleucine and ketoisoleucine. High amino acid turnover in glioma tumor tissue is currently utilized for PET imaging, diagnosis and delineation of tumor margins. By examining blood-based metabolic progression patterns towards disease onset, we demonstrate that this high amino acid turnover is also detectable in a simple blood sample. These findings provide additional insight of metabolic alterations during glioma development and progression.
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Biomarcadores de Tumor , Neoplasias Encefálicas , Glioma , Humanos , Glioma/sangre , Glioma/cirugía , Glioma/diagnóstico , Glioma/patología , Neoplasias Encefálicas/sangre , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/metabolismo , Masculino , Femenino , Biomarcadores de Tumor/sangre , Persona de Mediana Edad , Adulto , Progresión de la Enfermedad , Aminoácidos/sangre , Aminoácidos/metabolismoRESUMEN
BACKGROUND: The radiogenomic analysis has provided valuable imaging biomarkers with biological insights for gliomas. The radiogenomic markers for molecular profile such as DNA methylation remain to be uncovered to assist the molecular diagnosis and tumor treatment. METHODS: We apply the machine learning approaches to identify the magnetic resonance imaging (MRI) features that are associated with molecular profiles in 146 patients with gliomas, and the fitting models for each molecular feature (MoRad) are developed and validated. To provide radiological annotations for the molecular profiles, we devise two novel approaches called radiomic oncology (RO) and radiomic set enrichment analysis (RSEA). RESULTS: The generated MoRad models perform well for profiling each molecular feature with radiomic features, including mutational, methylation, transcriptional, and protein profiles. Among them, the MoRad models have a remarkable performance in quantitatively mapping global DNA methylation. With RO and RSEA approaches, we find that global DNA methylation could be reflected by the heterogeneity in volumetric and textural features of enhanced regions in T2-weighted MRI. Finally, we demonstrate the associations of global DNA methylation with clinicopathological, molecular, and immunological features, including histological grade, mutations of IDH and ATRX, MGMT methylation, multiple methylation-high subtypes, tumor-infiltrating lymphocytes, and long-term survival outcomes. CONCLUSIONS: Global DNA methylation is highly associated with radiological profiles in glioma. Radiogenomic global methylation is an imaging-based quantitative molecular biomarker that is associated with specific consensus molecular subtypes and immune features.
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Neoplasias Encefálicas , Metilación de ADN , Glioma , Imagen por Resonancia Magnética , Humanos , Glioma/genética , Glioma/inmunología , Metilación de ADN/genética , Femenino , Masculino , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/patología , Persona de Mediana Edad , Adulto , Aprendizaje Automático , Fenotipo , Anciano , Biomarcadores de Tumor/genéticaAsunto(s)
Aprobación de Drogas , Glioma , Isocitrato Deshidrogenasa , United States Food and Drug Administration , Estados Unidos , Humanos , Glioma/tratamiento farmacológico , Isocitrato Deshidrogenasa/antagonistas & inhibidores , Isocitrato Deshidrogenasa/genética , Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológicoRESUMEN
BACKGROUND: Glioma is the most common brain tumor. IDH mutations occur frequently in glioma, indicating a more favorable prognosis. We aimed to explore energy metabolism-related genes in glioma to promote the research and treatment. METHODS: Datasets were obtained from TCGA and GEO databases. Candidate genes were screened by differential gene expression analysis, then functional enrichment analysis was conducted on the candidate genes. PPI was also carried out to help determine the target gene. GSEA and DO analysis were conducted in the different expression level groups of the target gene. Survival analysis and immune cell infiltrating analysis were performed as well. RESULTS: We screened 34 candidate genes and selected GLUD1 as the target gene. All candidate genes were significantly enriched in 10 KEGG pathways and 330 GO terms. GLUD1 expression was higher in IDH-mutant samples than IDH-wildtype samples, and higher in normal samples than tumor samples. Low GLUD1 expression was related to poor prognosis according to survival analysis. Most types of immune cells were negatively related to GLUD1 expression, but monocytes and activated mast cells exhibited significantly positive correlation with GLUD1 expression. GLUD1 expression was significantly related to 119 drugs and 6 immune checkpoint genes. GLUD1 was able to serve as an independent prognostic indicator of IDH-mutant glioma. CONCLUSION: In this study, we identified an energy metabolism-related gene GLUD1 potentially contributing to favorable clinical outcomes of IDH-mutant glioma. In glioma, GLUD1 related clinical outcomes and immune landscape were clearer, and more valuable information was provided for immunotherapy.
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Neoplasias Encefálicas , Metabolismo Energético , Glioma , Isocitrato Deshidrogenasa , Mutación , Glioma/genética , Glioma/metabolismo , Humanos , Isocitrato Deshidrogenasa/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Metabolismo Energético/genética , Metabolismo Energético/fisiología , Pronóstico , Glutamato Deshidrogenasa/genética , Glutamato Deshidrogenasa/metabolismoRESUMEN
Objectives: This study aims to develop brain-targeted temozolomide (TMZ) nanograins using the biodegradable polymer material PEG-PLA as a carrier. The model drug TMZ was encapsulated within the polymer using targeted nanotechnology. Key characteristics such as appearance, particle size, size distribution, drug loading capacity, in vitro release rate, stability, and anti-tumor effects were systematically evaluated through in vitro experiments. Methods: Transmission electron microscopy (TEM) and Malvern size analyzer were employed to observe the morphological and particle size features of the TMZ nanospheres at various time points to assess stability. The effects of TMZ nanograins on glioma cell viability and apoptosis were evaluated using MTT assays and flow cytometry. Results: The targeted TMZ nano-micelles were successfully synthesized. After loading and targeted modifications, the particle size increased from 50.7 to 190 nm, indicating successful encapsulation of TMZ. The average particle size of the nano-micelles remained stable around 145 ± 10 nm at 1 day, 15 days, and 30 days post-preparation. The release rate of the nano-micelles was monitored at 2 h, 12 h, 24 h, and 48 h post-dialysis, ultimately reaching 95.8%. Compared to TMZ alone, the TMZ-loaded PEG-PLA nano-micelles exhibited enhanced cytotoxicity and apoptosis in glioma cells. This was accompanied by increased mitochondrial membrane potential and reactive oxygen species (ROS) levels following treatment with the TMZ nano-micelles. Conclusions: TMZ-loaded nano-micelles demonstrated a gradual release profile and significantly enhanced inhibitory effects on human glioma U251 cells compared to TMZ alone. The findings suggest that TMZ-loaded PEG-PLA nano-micelles may offer a more effective therapeutic approach for glioma treatment.
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Antineoplásicos Alquilantes , Apoptosis , Glioma , Micelas , Tamaño de la Partícula , Polietilenglicoles , Temozolomida , Temozolomida/farmacología , Temozolomida/química , Humanos , Glioma/tratamiento farmacológico , Glioma/patología , Glioma/metabolismo , Línea Celular Tumoral , Polietilenglicoles/química , Polietilenglicoles/farmacología , Apoptosis/efectos de los fármacos , Antineoplásicos Alquilantes/farmacología , Antineoplásicos Alquilantes/química , Transferrina/química , Portadores de Fármacos/química , Supervivencia Celular/efectos de los fármacos , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Nanopartículas/química , Poliésteres/químicaRESUMEN
Tissue-agnostic, molecularly targeted therapies are becoming increasingly common in cancer treatment. The molecular drivers of some classes and subclasses of tumors are rapidly being uncovered in an era of deep tumor sequencing occurring at the time of diagnosis. When and how targeted therapies should fit within up-front cytotoxic chemotherapy and radiation paradigms is yet to be determined, because many of them have been studied in single-arm studies in patients with relapsed or refractory cancer. Infant high-grade gliomas (HGGs) are biologically and clinically distinct from older child and adult HGGs, and are divided into 3 molecular subgroups. Group 1 infant HGGs are driven by receptor tyrosine kinase fusions, most commonly harboring an ALK, ROS1, NTRK, or MET fusion. Both larotrectinib and entrectinib are tropomyosin receptor kinase inhibitors with tissue-agnostic approvals for the treatment of patients with solid tumors harboring an NTRK fusion. This report discusses an 11-month-old female who presented with infantile spasms, found to have an unresectable, NTRK fusion-positive infant HGG. Larotrectinib was prescribed when the NTRK fusion was identified at diagnosis, and without additional intervention to date, the patient has continued with stable disease for >3 years. The only adverse event experienced was grade 1 aspartate transaminase and alanine transaminase elevations. The patient has a normal neurologic examination, is developing age-appropriately in all domains (gross motor, fine motor, cognitive, language, and social-emotional). She is no longer on antiseizure medications. To our knowledge, this is the first report of a patient with an infantile HGG receiving targeted therapy as first-line treatment with prolonged stable disease. A prospective study of larotrectinib in patients with newly diagnosed infant HGG is ongoing, and will hopefully help answer questions about durability of response, the need for additional therapies, and long-term toxicities seen with TRK inhibitors.
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Glioma , Inhibidores de Proteínas Quinasas , Pirazoles , Pirimidinas , Receptor trkB , Humanos , Femenino , Lactante , Pirazoles/uso terapéutico , Glioma/tratamiento farmacológico , Glioma/genética , Glioma/patología , Receptor trkB/genética , Receptor trkB/antagonistas & inhibidores , Pirimidinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Proteínas de Fusión Oncogénica/genética , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Clasificación del Tumor , Resultado del Tratamiento , Glicoproteínas de Membrana/genéticaRESUMEN
OBJECTIVE: MR-guided focused ultrasound (MRgFUS) is an evolving technology with numerous present and potential applications in pediatric neurosurgery. The aim of this study was to describe the use of MRgFUS, technical challenges, complications, and lessons learned at a single children's hospital. METHODS: A retrospective analysis was performed of a prospectively collected database of all pediatric patients undergoing investigational use of MRgFUS for treatment of various neurosurgical pathologies at Children's National Hospital. Treatment details, clinical workflow, and standard operating procedures are described. Patient demographics, procedure duration, and complications were obtained through a chart review of anesthesia and operative reports. RESULTS: In total, 45 MRgFUS procedures were performed on 14 patients for treatment of diffuse intrinsic pontine glioma (n = 12), low-grade glioma (n = 1), or secondary dystonia (n = 1) between January 2022 and April 2024. The mean age at treatment was 9 (range 5-22) years, and 64% of the patients were male. With increased experience, the total anesthesia time, sonication time, and change in core body temperature during treatment all significantly decreased. Complications affected 4.4% of patients, including 1 case of scalp edema and 1 patient with a postprocedure epidural hematoma. Device malfunction requiring abortion of the procedure occurred in 1 case (2.2%). Technical challenges related to transducer malfunction and sonication errors occurred in 6.7% and 11.1% of cases, respectively, all overcome by subsequent user modifications. CONCLUSIONS: The authors describe the largest series on MRgFUS technical aspects in pediatric neurosurgery at a single institution, comprising 45 total treatments. This study emphasizes potential technical challenges and provides valuable insights into the nuances of its application in pediatric patients.
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Procedimientos Neuroquirúrgicos , Humanos , Niño , Masculino , Femenino , Adolescente , Preescolar , Procedimientos Neuroquirúrgicos/métodos , Estudios Retrospectivos , Adulto Joven , Hospitales Pediátricos , Glioma/cirugía , Glioma/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Neoplasias del Tronco Encefálico/cirugía , Neoplasias del Tronco Encefálico/diagnóstico por imagen , Distonía/cirugía , Distonía/diagnóstico por imagenRESUMEN
This study examined to evaluate the predictive value of a nomogram with Ki-67 in overall and disease-free survival in glioma patients, a total of 76 patients diagnosed with glioma by pathology in Tengzhou Central People's Hospital were enrolled. The baseline data and follow ups were retrospectively collected from medical records. The associations between Ki-67 and survival status were examined using log-rank test, univariate and multivariate Cox proportional hazard regression models. Calibrations were performed to validate the established nomograms. Ki-67 negative group showed of a longer OS survival time and a longer PFS survival time with log-rank test (x2 = 16.101, P < 0.001 and x2 = 16.961, P < 0.001). Age older than 50 years (HR = 2.074, 95% CI 1.097-3.923), abnormal treatment (HR = 2.932, 95% CI 1.343-6.403) and Ki-67 positive (HR = 2.722, 95% CI 1.097-6.755) were the independent predictive factors of death. High grade pathology (HR = 2.453, 95% CI 1.010-5.956) and Ki-67 positive (HR = 2.200, 95% CI 1.043-4.639) were the independent predictive factors of recurrence. The C-index for the nomogram of OS and PFS were 0.745 and 0.723, respectively. The calibration results showed that the nomogram could predict the overall and disease-free 1-year survival of glioma patients. In conclusion, the nomograms with Ki-67 as independent risk factor for OS and PFS could provide clinical consultation in the treatment and follow-up of malignant glioma.
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Neoplasias Encefálicas , Glioma , Antígeno Ki-67 , Recurrencia Local de Neoplasia , Nomogramas , Humanos , Glioma/mortalidad , Glioma/cirugía , Glioma/metabolismo , Glioma/patología , Antígeno Ki-67/metabolismo , Femenino , Masculino , Persona de Mediana Edad , Adulto , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Estudios Retrospectivos , Anciano , Pronóstico , Supervivencia sin Enfermedad , Modelos de Riesgos ProporcionalesRESUMEN
Chromosomal instability (CIN) is a pivotal factor in gliomas, contributing to their complexity, progression, and therapeutic challenges. CIN, characterized by frequent genomic alterations during mitosis, leads to genetic abnormalities and impacts cellular functions. This instability results from various factors, including replication errors and toxic compounds. While CIN's role is well documented in cancers like ovarian cancer, its implications for gliomas are increasingly recognized. CIN influences glioma progression by affecting key oncological pathways, such as tumor suppressor genes (e.g., TP53), oncogenes (e.g., EGFR), and DNA repair mechanisms. It drives tumor evolution, promotes inflammatory signaling, and affects immune interactions, potentially leading to poor clinical outcomes and treatment resistance. This review examines CIN's impact on gliomas through a narrative approach, analyzing data from PubMed/Medline, EMBASE, the Cochrane Library, and Scopus. It highlights CIN's role across glioma subtypes, from adult glioblastomas and astrocytomas to pediatric oligodendrogliomas and astrocytomas. Key findings include CIN's effect on tumor heterogeneity and its potential as a biomarker for early detection and monitoring. Emerging therapies targeting CIN, such as those modulating tumor mutation burden and DNA damage response pathways, show promise but face challenges. The review underscores the need for integrated therapeutic strategies and improved bioinformatics tools like CINdex to advance understanding and treatment of gliomas. Future research should focus on combining CIN-targeted therapies with immune modulation and personalized medicine to enhance patient outcomes.
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Neoplasias Encefálicas , Inestabilidad Cromosómica , Progresión de la Enfermedad , Glioma , Humanos , Glioma/genética , Glioma/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologíaRESUMEN
Flow cytometry is a vital tool in biomedical research and laboratory medicine. However, its accuracy is often compromised by undesired fluctuations in fluorescence intensity. While fluorescence lifetime imaging microscopy (FLIM) bypasses this challenge as fluorescence lifetime remains unaffected by such fluctuations, the full integration of FLIM into flow cytometry has yet to be demonstrated due to speed limitations. Here we overcome the speed limitations in FLIM, thereby enabling high-throughput FLIM flow cytometry at a high rate of over 10,000 cells per second. This is made possible by using dual intensity-modulated continuous-wave beam arrays with complementary modulation frequency pairs for fluorophore excitation and acquiring fluorescence lifetime images of rapidly flowing cells. Moreover, our FLIM system distinguishes subpopulations in male rat glioma and captures dynamic changes in the cell nucleus induced by an anti-cancer drug. FLIM flow cytometry significantly enhances cellular analysis capabilities, providing detailed insights into cellular functions, interactions, and environments.
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Citometría de Flujo , Glioma , Citometría de Flujo/métodos , Animales , Ratas , Glioma/diagnóstico por imagen , Glioma/patología , Glioma/metabolismo , Masculino , Microscopía Fluorescente/métodos , Línea Celular Tumoral , Imagen Óptica/métodos , Humanos , Núcleo Celular/metabolismo , Ensayos Analíticos de Alto Rendimiento/métodos , Colorantes Fluorescentes/químicaRESUMEN
OBJECTIVE: To evaluate the performance of magnetic resonance imaging (MRI) multi-sequence feature imputation and fusion mutual model based on sequence deletion in differentiating high-grade glioma (HGG) from low-grade glioma (LGG). METHODS: We retrospectively collected multi-sequence MR images from 305 glioma patients, including 189 HGG patients and 116 LGG patients. The region of interest (ROI) of T1-weighted images (T1WI), T2-weighted images (T2WI), T2 fluid attenuated inversion recovery (T2_FLAIR) and post-contrast enhancement T1WI (CE_T1WI) were delineated to extract the radiomics features. A mutual-aid model of MRI multi-sequence feature imputation and fusion based on sequence deletion was used for imputation and fusion of the feature matrix with missing data. The discriminative ability of the model was evaluated using 5-fold cross-validation method and by assessing the accuracy, balanced accuracy, area under the ROC curve (AUC), specificity, and sensitivity. The proposed model was quantitatively compared with other non-holonomic multimodal classification models for discriminating HGG and LGG. Class separability experiments were performed on the latent features learned by the proposed feature imputation and fusion methods to observe the classification effect of the samples in twodimensional plane. Convergence experiments were used to verify the feasibility of the model. RESULTS: For differentiation of HGG from LGG with a missing rate of 10%, the proposed model achieved accuracy, balanced accuracy, AUC, specificity, and sensitivity of 0.777, 0.768, 0.826, 0.754 and 0.780, respectively. The fused latent features showed excellent performance in the class separability experiment, and the algorithm could be iterated to convergence with superior classification performance over other methods at the missing rates of 30% and 50%. CONCLUSION: The proposed model has excellent performance in classification task of HGG and LGG and outperforms other non-holonomic multimodal classification models, demonstrating its potential for efficient processing of non-holonomic multimodal data.
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Neoplasias Encefálicas , Glioma , Imagen por Resonancia Magnética , Humanos , Glioma/diagnóstico por imagen , Glioma/patología , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Algoritmos , Clasificación del Tumor , Curva ROC , Sensibilidad y EspecificidadRESUMEN
Stereotactic Brachytherapy Iodine-125 (SBT I-125) has been investigated by some studies for the treatment of lowgrade gliomas. We performed a meta-analysis to assess the efficacy and safety of SBT I-125 Brachytherapy for treatment of patients with Low-Grade Gliomas. PubMed, Cochrane, Web of Science, and EMBASE databases were searched for randomized and observational studies. This systematic review and meta-analysis was conducted according to the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. We used relative risk (RR) with 95% confidence intervals and random effects model to compare the effects of I-125 SBT treatment on the interest outcomes. We evaluated heterogeneity using I2 statistics; we considered heterogeneity to be significant if the p-value was less than 0.05 and I2 was higher than 35%. We performed statistical analysis using the software R (version 4.2.3). A total of 20 studies with a cohort of 988 patients with low grade gliomas who received SBT I-125 as a treatment option. The pooled analysis evidenced: (1) Complication rate of 10% (95% CI: 7-12%; I² = 60%); (2) 5-year PFS of 66% (99% CI: 45-86%; I²= 98%); (3) 10-year PFS was 66% (99% CI: 45-86%; I²= 98%); (4) Malignant transformation rate of 26% (95% CI: 8-45%; I²=0); (5) Mortality of 33% (95% CI: 15-51%; I² = 0%). Our systematic review and meta-analysis of SBT I-125 for low-grade gliomas have revealed significant concerns regarding its safety and efficacy. Despite a proportion of patients remaining progression-free, elevated rates of complications and mortality cast doubt on the intervention's reliability. Future research should prioritize long-term follow-up studies, standardized protocols, and comparative effectiveness research.
Asunto(s)
Braquiterapia , Neoplasias Encefálicas , Glioma , Radioisótopos de Yodo , Humanos , Glioma/radioterapia , Glioma/patología , Braquiterapia/métodos , Radioisótopos de Yodo/uso terapéutico , Neoplasias Encefálicas/radioterapia , Resultado del TratamientoRESUMEN
OBJECTIVE: To assess the clinical efficacy of combined microsurgery and postoperative radiotherapy for the treatment of intramedullary spinal gliomas and its impact on neurological function. STUDY DESIGN: An observational study. Place and Duration of the Study: Department of Neurosurgery, Baoding No.1 Central Hospital, Hebei, China, between January 2020 and 2023. METHODOLOGY: Sixty patients diagnosed with spinal cord intramedullary gliomas were divided equally into an experimental and control group. The control group received microsurgical treatment, and the experimental group received microsurgical treatment combined with postoperative radiotherapy. The treatment effectiveness, neurological function, and follow-up results of the two groups were compared. RESULTS: After treatment, the clinical efficacy of the experimental group treatment was significantly better than that of the control group (p <0.05). The National Institutes of Health Stroke Scale (NIHSS) scores were significantly lower, and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-30 (EORTC QLQ-C30) scores were significantly higher in the experimental group than in the control group (p <0.05). The 1-3-year survival rate and median survival time of the experimental group were significantly higher than those of the control group (p <0.05). The incidence of complications was 3.33% in the experimental group and 6.67% in the control group, but the difference was not statistically significant (p >0.05). The postoperative recurrence rate was significantly lower in the experimental (0%) than in the control group (13.33%, p <0.05). CONCLUSION: Combined microsurgery and postoperative radiotherapy was found to be more effective than microsurgery alone. It was also more conducive to the recovery of neurological function and improved the patient's quality of life. KEY WORDS: Intramedullary spinal cord glioma, Microsurgery, Neurological function, Radiotherapy.
Asunto(s)
Glioma , Microcirugia , Calidad de Vida , Neoplasias de la Médula Espinal , Humanos , Neoplasias de la Médula Espinal/cirugía , Neoplasias de la Médula Espinal/radioterapia , Microcirugia/métodos , Masculino , Femenino , Persona de Mediana Edad , Glioma/cirugía , Glioma/radioterapia , Adulto , Resultado del Tratamiento , Radioterapia Adyuvante , China/epidemiologíaRESUMEN
Brain tumour diagnosis involves assessing various radiological and histopathological parameters. Imaging modalities are an excellent resource for disease monitoring. However, manual inspection of imaging is laborious, and performance varies depending on expertise. Artificial Intelligence (AI) driven solutions a non-invasive and low-cost technology for diagnostics compared to surgical biopsy and histopathological diagnosis. We analysed various machine learning models reported in the literature and assess its applicability to improve neuro-oncological management. A scoping review of 47 full texts published in the last 3 years pertaining to the use of machine learning for the management of different types of gliomas where radiomics and radio genomic models have proven to be useful. Use of AI in conjunction with other factors can result in improving overall neurooncological management within LMICs. AI algorithms can evaluate medical imaging to aid in the early detection and diagnosis of brain tumours. This is especially useful where AI can deliver reliable and efficient screening methods, allowing for early intervention and treatment.