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@#Objective To analyze the mechanism of Biochanin A in the treatment of Gliomas based on network pharmacology and molecular docking.Methods Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),TargetNet,Swiss Target Prediction were used to search the active components and targets of Biochanin A.DisGeNET,GeneCards databases were used to search the corresponding targets of Gliomas.The intersection of active components of Biochanin A and gliomas target were selected to obtain the potential target of Biochanin A in treating Gliomas.Protein gene interaction data were obtained by STRING database,and protein-protein interaction network was constructed by importing into Cytoscape software.Gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of the same target proteins of drug and disease were carried out by DAVID database.Molecular docking was performed by using DockThor and Pymol software.Results A total of 149 targets of Biochanin A,5654 gliomas relate-genes,97 common targets of Biochanin A and gliomas are collected.The key targets were epidermal growth factor receptor(EGFR),estrogen receptor(ESR1),heat shock protein(HSP)90AA1,matrix metalloproteinase(MMP)9,PPARG and PTGS2.The targets were mainly play an essential role in cell proliferation,invasion,cell apoptosis,and other biological pathways.GO enrichment analysis demonstrated that Biochanin A could involve the treatment of Gliomas in biological process,cell composition and molecular function.KEGG 108 signaling pathways mainly related to pathways in cancer,chemical carcinogenesis-receptor activation,Lipid and atherosclerosis,PI3K/Akt pathway.Molecular docking indicated that Biochanin A had a good bonding activity with the key targets.Conclusion Biochanin A may play a role in the treatment of glioma by inhibiting tumor cell proliferation,inducing apoptosis and enhancing chemotherapy sensitivity.The study built a foundation for drug development and innovative research.
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Objetivo: presentar los avances diagnósticos, moleculares y radiológicos, así como en las estrategias terapéuticas para gliomas difusos en los últimos 5 años (2018-2023) en la Fundación Universitaria de Ciencias de la Salud (FUCS), Bogotá D.C., Colombia. Materiales y métodos: se describen las técnicas diagnósticas y terapéuticas utilizadas para gliomas difusos con casos ilustrativos. Resultados: se muestran los avances de las herramientas diagnósticas y terapéuticas para el manejo de gliomas difusos. Discusión: en los últimos 5 años se ha avanzado en la clasificación, diagnóstico y tratamiento de los gliomas difusos, gracias a los avances tecnológicos como los marcadores moleculares, la tractografía y la fusión de imágenes para la neuronavegación y las técnicas de estimulación cortical. Esto ha permitido que el tratamiento de los pacientes con dichos tumores mejore la tasa de morbilidad, la calidad de vida libre de enfermedad y la supervivencia global. Conclusiones: las técnicas de diagnóstico como la tractografía, la fusión integral de imágenes intraoperatorias y el mapeo cerebral electrofisiológico con estimulación cortical y subcortical han mejorado el diagnóstico y tratamiento de los gliomas difusos.
Objective: to present the diagnostic, molecular, radiological, and therapeutic advances, to address diffuse gliomas, made at Fundación Universitaria de Ciencias de la Salud (FUCS), Bogotá D.C., Colombia, in the last 5 years (2018-2023). Materials and methods: diagnostic and therapeutic techniques to address diffuse gliomas are described through illustrative cases. Results: the advances in diagnostic and therapeutic tools for managing diffuse gliomas, are shown. Discussion: in the last 5 years progress in characterizing, diagnosing, and treating diffuse gliomas, thanks to technological breakthroughs, such as molecular markers, tractography, image fusion for neuronavigation, and cortical stimulation techniques, has been achieved. This has allowed improving morbidity rate, disease-free quality of life and overall survival through the treatment provided to patients afflicted with gliomas. Conclusions: Diagnostic techniques based on tractography, comprehensive intraoperative image fusion, and electrophysiological brain mapping with cortical and subcortical stimulation, have improved the diagnostic and therapeutic approaches for diffuse gliomas.
Subject(s)
HumansABSTRACT
Background Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), are present in most gliomas. IDH1 mutation is an important prognostic marker in glioma. However, its regulatory mechanism in glioma remains incompletely understood. Results miR-182-5p expression was increased within IDH1-mutant glioma specimens according to TCGA, CGGA, and online dataset GSE119740, as well as collected clinical samples. (R)-2-hydroxyglutarate ((R)-2HG) treatment up-regulated the expression of miR-182-5p, enhanced glioma cell proliferation, and suppressed apoptosis; miR-182-5p inhibition partially eliminated the oncogenic effects of R-2HG upon glioma cells. By direct binding to Cyclin Dependent Kinase Inhibitor 2 C (CDKN2C) 3'UTR, miR-182-5p inhibited CDKN2C expression. Regarding cellular functions, CDKN2C knockdown promoted R-2HG-treated glioma cell viability, suppressed apoptosis, and relieved cell cycle arrest. Furthermore, CDKN2C knockdown partially attenuated the effects of miR-182-5p inhibition on cell phenotypes. Moreover, CDKN2C knockdown exerted opposite effects on cell cycle check point and apoptosis markers to those of miR-182-5p inhibition; also, CDKN2C knockdown partially attenuated the functions of miR-182-5p inhibition in cell cycle check point and apoptosis markers. The engineered CS-NPs (antagomir-182-5p) effectively encapsulated and delivered antagomir-182-5p, enhancing anti-tumor efficacy in vivo, indicating the therapeutic potential of CS-NPs(antagomir-182-5p) in targeting the miR-182-5p/CDKN2C axis against R-2HG-driven oncogenesis in mice models. Conclusions These insights highlight the potential of CS-NPs(antagomir-182-5p) to target the miR-182-5p/CDKN2C axis, offering a promising therapeutic avenue against R-2HG's oncogenic influence to glioma.
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Abstract The purpose of this pictorial essay is to describe the recommendations of the 2021 World Health Organization classification for adult-type and pediatric-type gliomas and to discuss the main modifications in relation to the previous (2016) classification, exemplified by imaging, histological, and molecular findings in nine patients followed at our institutions. In recent years, molecular biomarkers have gained importance in the diagnosis and classification of gliomas, mainly because they have been shown to correlate with the biological behavior and prognosis of such tumors. It is important for neuroradiologists to familiarize themselves with this new classification of central nervous system tumors, so that they can use this knowledge in evaluating and reporting the imaging examinations of patients with glioma.
Resumo O propósito deste ensaio iconográfico é descrever e discutir as novas recomendações da Organização Mundial da Saúde de 2021, referente aos gliomas dos tipos adulto e infantil, e suas principais diferenças com a classificação anterior (2016), exemplificadas com imagens de nove casos de pacientes atendidos nas nossas instituições. Recentemente, há uma crescente significância dos marcadores moleculares no diagnóstico e classificação dos gliomas e tumores do sistema nervoso central, principalmente pela correlação com o comportamento biológico e o prognóstico. É importante que os neurorradiologistas estejam familiarizados com a nova classificação dos tumores do sistema nervoso central para a prática clínica, na avaliação e emissão de laudos e opiniões nas imagens dos pacientes com gliomas.
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Resumen En 2021 se publicó la última versión de la clasificación de tumores del sistema nervioso central de la Organización Mundial de la Salud (WHO CNS5 por sus siglas en inglés), considerada un estándar internacional. Las primeras ediciones se basaron en características histológicas y posteriormente se incorporaron aspectos relacionados con nuevos conocimientos. En la revisión de 2016 se implementaron características moleculares para la clasificación y estadificación de los gliomas, como la presencia de mutaciones en IDH1 y IDH2. Actualmente, las técnicas de resonancia magnética avanzada permiten valorar la presencia de 2-HG (oncometabolito incrementado ante mutaciones en IDH), de forma que indirectamente y sin procedimientos invasivos pueden identificarse las mutaciones en IDH. La resonancia magnética avanzada es un procedimiento aún en desarrollo, de gran utilidad para el diagnóstico y manejo de distintas patologías. En el presente documento se abordan las implicaciones de la WHO CNS5 en la evaluación de gliomas, así como aspectos históricos, las bases de la resonancia magnética convencional y secuencias de resonancia magnética avanzada útiles en la clasificación actual.
Abstract In 2021, the latest version of the World Health Organization classification of central nervous system tumors (WHO CNS5) was published, which is considered an international standard. The first editions of this classification were based on histological characteristics and, subsequently, aspects related to new knowledge were incorporated. In the 2016 revision, molecular characteristics were implemented for the classification and staging of gliomas, such as the presence of mutations in IDH1 or IDH2. Currently, advanced magnetic resonance imaging (MRI) techniques allow assessing for the presence of 2-HG (increased oncometabolite that precedes IDH mutations), whereby IDH mutations can be indirectly identified, without invasive procedures being required. Advanced MRI is a growing field, highly useful for diagnosis and management of different pathologies. This document addresses the implications of WHO CNS5 classification in the evaluation of gliomas, as well as historical aspects, the bases of conventional MRI, and advanced MRI sequences useful in current classification.
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Introdução: Os gliomas são tumores encefálicos e da medula espinhal que se originam nas células gliais e cuja progressão invade o tecido cerebral adjacentee e dentre eles um dos mais desafiadores são localizados no lobo cerebral da ínsula. Estas artérias irrigam estruturas nobres e sua lesão pode produzir danos sensitivos, motores e de linguagem. Objetivo: Descrever o impacto da extensão da ressecção, sobrevida global e dos resultados funcionais após a cirurgia dos gliomas insulares, quando estes tumores estejam ou não envolvidos pelas artérias lenticuloestriadas. Métodos: Revisão integrativa nas plataformas virtuais em português e inglês, buscando AND ou OR dados através dos seguintes descritores "Gliomas da ínsula, Mapeamento cerebral, Artérias lenticuloestriadas". A busca inicial foi baseada no título e/ou resumo. Decididos os trabalhos incluíveis foi realizada a leitura na íntegra dos textos. Ao total foram estudados 55 artigos. Resultados: O lobo da ínsula fica "escondido" pela sobreposição dos lobos frontal, parietal e temporal. Para alcançá-lo pode-se realizar as abordagens transsilviana ou transcortical. Ocorre que ao chegar na ínsula visualiza-se significativa ramificação constituída pelas artérias lenticuloestriadas, cuja manipulação pode determinar déficit neurológico e, ao se aprofundar no córtex insular, depara-se com outras estruturas tão importantes quanto a própria ínsula. O conhecimento anatômico das artérias lenticuloestriadas e suas relações é de fundamental importância para a ressecção de glioma insular, pois o comprometimento delas e da artéria cerebral média podem determinar a isquemia dos núcleos da base e da cápsula interna. Conclusão: O tratamento dos gliomas insulares permanece como grande desafio. Devido à sua localização e possibilidade de desenvolvimento de déficits neurológicos na manipulação cirúrgica é necessário não somente conhecer sua localização topográfica, mas também a íntima relação vascular com as artérias lenticuloestriadas. O envolvimento delas pelo tumor possui implicações na sobrevida e na preservação da função neurológica. O conhecimento detalhado da anatomia da região é fundamental para diminuir complicações que afetem grandemente a qualidade de vida dos pacientes.
Introduction: Gliomas are brain and spinal cord tumors that originate in glial cells and whose progression invades the adjacent brain tissue and among them one of the most challenging are located in the cerebral lobe of the insula. These arteries supply noble structures and their damage can cause sensory, motor and language damage. Objective: To describe the impact of the extent of resection, overall survival and functional results after surgery for insular gliomas, when these tumors are or are not involved by lenticulostriate arteries. Methods: Integrative review on virtual platforms in Portuguese and English, searching for AND or OR data using the following descriptors "Insula gliomas, Brain mapping, Lenticulostriate arteries". The initial search was based on the title and/or abstract. Once the included works were decided, the texts were read in full. In total, 55 articles were studied. Results: The insula lobe is "hidden" by the overlap of the frontal, parietal and temporal lobes. To achieve this, transsylvian or transcortical approaches can be performed. It turns out that when arriving at the insula, a significant branch made up of lenticulostriate arteries is seen, the manipulation of which can cause neurological deficits and, when going deeper into the insular cortex, one comes across other structures as important as the insula itself. Anatomical knowledge of the lenticulostriate arteries and their relationships is of fundamental importance for the resection of insular glioma, as their involvement and that of the middle cerebral artery can determine ischemia of the basal ganglia and internal capsule. Conclusion: The treatment of insular gliomas remains a major challenge. Due to its location and the possibility of developing neurological deficits during surgical manipulation, it is necessary not only to know its topographic location, but also the intimate vascular relationship with the lenticulostriate arteries. Their involvement by the tumor has implications for survival and preservation of neurological function. Detailed knowledge of the region's anatomy is essential to reduce complications that greatly affect patients' quality of life.
Subject(s)
Cerebral Arteries , Insular CortexABSTRACT
The fifth edition of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System (WHO CNS5) features several changes in the classification, diagnostic criteria, nomenclature, and grading of diffuse gliomas. Adult-type diffuse gliomas are genetically defined and include astrocytoma, isocitrate dehydrogenase (IDH)-mutant, oligodendroglioma, IDH-mutant and 1p/19q codeleted, and glioblastoma, IDH-wildtype. This review briefly discusses two tumor types: astrocytoma, IDH-mutant, and oligodendroglioma, IDH-mutant and 1p/19q codeleted, with emphasis on relevant changes in their classification and defining molecular genetic alterations. A simplified approach to the diagnosis of these tumors is provided.
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Background/Aim: High-grade gliomas are aggressive brain neoplasms usually refractory to treatment. Recently new treatment approaches have emerged, including immunotherapies. Hence, the aim of the present study was to evaluate the efficacy and safety of immunotherapies in adult patients with high-grade gliomas. Methods: Searches were performed in three databases for relevant studies published until December 2020. Title and abstract screening, full-text review, data extraction, and risk of bias assessment were performed independently by two reviewers. Risk of bias assessment was performed according to the revised Cochrane risk-of-bias tool for randomized trials (RoB 2). Meta-analyses were performed with Review Manager software (version 5.4.1), using risk ratio and 95% confidence intervals as measure of effect, the Mantel-Haenszel method, and random effects models. The quality of evidence assessment was conducted according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Nineteen studies were included in the systematic review, of which 15 reported comparable data for meta-analyses. The outcomes assessed in the meta-analyses were overall survival (OS) and progression-free survival (PFS), with subgroups at 6, 12, and more than 12 months. No statistical differences were observed between immunotherapy and conventional treatment, except for the OS subgroup over 12 months. The certainty on the evidence was moderate. Conclusion: There was no evidence of an additional benefit of immunotherapy compared to standard treatment in the synthesis of results from clinical trials. Further high-quality clinical trials are needed to improve the quality of evidence concerning immunotherapies for the treatment of high-grade gliomas.
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Objective:To analyze the clinic-pathological features and surgical outcomes of adult patients with hypothalamic gliomas.Methods:The adult cases pathologically confirmed as hypothalamic gliomas were analyzed from October, 2011 to January, 2022 in Beijing Tiantan Hospital.Results:There were 32 adult cases with hypothalamic gliomas, including 16 males and 16 females. Tumor was located in the hypothalamus in 6 cases, in the hypothalamus plus optic chiasma/nerve in 6 cases, in the hypothalamus plus thalamus in 9 cases, and in the hypothalamus plus the third ventricle in 11 cases. Pre-operative hydrocephalus was found in 20 cases. Five patents underwent stereotactic biopsy, 27 patients underwent craniotomy, and 11 patients underwent shunt surgery for hydrocephalus. Of 27 patients with craniotomy, trans-callosal approach was chosen for 9 patients, trans-cortical for 8 patients, via pterion approach for 4 patients, via lateral sub-frontal approach for 4 patients, via fissurae interhemisphaerica for 1 patient, and trans-sphenoidal approach for 1 patient. Twenty-two patients received gross-total or subtotal resection, 5 patients received partial resection. All the patients were pathologically confirmed, including 9 patients with high-grade and 23 patients with low-grade gliomas. Six patients died within 3 months after craniotomy, 8 patients suffered from endocrine dysfunction, 7 patients suffered from electrolyte disturbance, and 5 patients suffered from hydrocephalus. They were followed for 0.7-110.0 months, with 5-year progression-free survival rate of 63.8% and 5-year overall survival rate of 53.9% for all patients. The 5-year progression-free survival rate was 83.3% and the 5-year overall survival rate was 72.8% for low-grade gliomas.Conclusions:The peri-operative mortality is high for adult patients with hypothalamic gliomas, and protection of the hypothalamic function is important. Patients with low-grade hypothalamic gliomas have good prognoses.
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Background and aim: Gliomas are the most common primary brain tumors, classified according to their histopathological and genetic features. Tumorigenesis depends on alterations in different genes. The aim of this study was the identification of mutations in IDH1 and TERT genes in gliomas of Argentine patients and to correlate them with clinical features and prognosis. Methods: DNA was isolated from 19 biopsies with different glioma grades matched with blood samples. IDH1 and TERT mutations were studied by PCR amplifica-tion and sequencing. Results: Six out of seven patients with low-grade glioma (grade II) harbor IDH1 mutations, mainly without tumor growth and overall survival of more than 12 months. Eleven out of twelve patients with high-grade gliomas (grade III/IV) showed wild type IDH1, mainly with tumor growth and shorter survival than low-grade gliomas. Mutated TERT promoter was present in 5 out of 11 high-grade gliomas, showing the prevalence of polymorphic C allele. In 1 out of 5 low-grade gliomas with a predominance of T allele. TERT and IDH1 mutations were mutually exclusive in most gliomas. Conclusions: Our results show that genetic tests provided a more accurate prognosis than histopathological analysis. The evolution of gliomas can be predicted primarily by the mutational status of IDH1 and secondarily by other markers, such as TERT mutational status
Antecedentes y objetivo: los gliomas son los tumores cerebrales primarios más comunes y se clasifican según sus características histopatológicas y genéticas. La tumorigénesis depende de alteraciones en diferentes genes. El objetivo de este estudio fue identificar mutaciones en los genes IDH1 y TERT en gliomas de pacientes argentinos y correlacionarlos con la evolución clínica. Métodos: se obtu-vieron 19 muestras pareadas de ADN de gliomas y de la sangre. Las mutaciones en IDH1 y TERT se analizaron por PCR y secuenciación. Resultados: la IDH1 mutada se encontró en 6 de los 7 gliomas de bajo grado (grado II), mayormente sin crecimiento tumoral y una sobrevida mayor de 12 meses. La IDH1 salvaje estaba presente en 11 de los 12 gliomas de alto grado (grado III y IV) mayormente con crecimiento tumoral y menor sobrevida que los tumores de bajo grado. Las mutaciones en el promotor del gen TERT se observaron en 5 de los 11 gliomas de alto grado, con la prevalencia de alelo polimórfico C, en cambio, en gliomas de bajo grado TERT mutado estaba presente en 1 de los 5 gliomas con predominio del alelo T. Las mutaciones en IDH1 y TERT fueron mutuamente excluyentes en la mayoría de los gliomas. Conclusiones: el análisis genético provee un pronóstico más certero que el análisis histopatológico. Nuestros resulta-dos muestran que la evolución de gliomas puede predecirse primariamente por el estado mutacional de IDH1 y secundariamente por mutaciones en otros marcadores tales como el TERT
Subject(s)
Patients , Sampling Studies , Glioma , Mutation , Argentina , Prognosis , CarcinogenesisABSTRACT
Cancer cell lines are widely used as in vitro models of tumorigenesis, facilitating fundamental discoveries in cancer biology and translational medicine. Currently, there are few options for glioblastoma (GBM) treatment and limited in vitro models with accurate genomic and transcriptomic characterization. Here, a detailed characterization of a new GBM cell line, namely AHOL1, was conducted in order to fully characterize its molecular composition based on its karyotype, copy number alteration (CNA), and transcriptome profiling, followed by the validation of key elements associated with GBM tumorigenesis. Large numbers of CNAs and differentially expressed genes (DEGs) were identified. CNAs were distributed throughout the genome, including gains at Xq11.1-q28, Xp22.33-p11.1, Xq21.1-q21.33, 4p15.1-p14, 8q23.2-q23.3 and losses at Yq11.21-q12, Yp11.31-p11.2, and 15q11.1-q11.2 positions. Nine druggable genes were identified, including HCRTR2, ETV1, PTPRD, PRKX, STS, RPS6KA6, ZFY, USP9Y, and KDM5D. By integrating DEGs and CNAs, we identified 57 overlapping genes enriched in fourteen pathways. Altered expression of several cancer-related candidates found in the DEGs-CNA dataset was confirmed by RT-qPCR. Taken together, this first comprehensive genomic and transcriptomic landscape of AHOL1 provides unique resources for further studies and identifies several druggable targets that may be useful for therapeutics and biologic and molecular investigation of GBM.
Subject(s)
Humans , Glioblastoma/genetics , Gene Expression Regulation, Neoplastic , Minor Histocompatibility Antigens , Genome , Genomics , Cell Line, Tumor , Histone Demethylases , TranscriptomeABSTRACT
@#[Abstract] Objective: To explore the effect of exosome-derived miR-181a on angiogenesis and tumor progression in gliomas. Methods: 83 cases of glioma tissues and 13 cases of peritumoral tissues resected in the Second Affiliated Hospital of Hainan Medical University from August 2017 to December 2019, glioma cells U87, A172, U251, LN229, U373 and microglial cell line HM, were selected to detect the expression of miR-181a in tumor tissues and cells by qPCR method. Glioma U373 cells with miR-181a over-expression or knockdown were constructed, and exosomes were isolated and identified. The effects of exsome-derived miR-181a on angiogenesis of HUVEC cells were investigated by tubule formation and chicken chorioallantoic membrane assay in vitro. Nude mice bearing U373 cell transplanted xenograft was constructed to observe the effect of exsome-derived miR-181a on angiogenesis and tumor growth in vivo. Results: The expression of miR-181a in glioma tissues and cells was significantly higher than that in normal tissues and normal glial HM cells (all P<0.01). The exsome-derived miR-181a could significantly promote the tubule formation of HUVEC cells (P<0.01) and the angiogenesis of chicken chorioallantoic membrane (all P<0.01). In vivo experiments showed that the growth of xenografts was promoted (P<0.05) and the amount of angiogenesis in the tumor tissues was increased in the nude mice after being transfused with exsome-derived miR-181a (P<0.01). Conclusion: miR-181a plays an important role in promoting angiogenesis of gliomas and may be a potential target for diagnosis and treatment of gliomas.
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Objective:To investigate the clinical application value of blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) to the protection of language function in patients with unilateral frontal and temporal lobes glioma receiving postoperative intensity modulation radiation therapy (IMRT).Methods:A total of 27 patients with unilateral frontal and temporal lobe gliomas were treated with postoperative radiotherapy. The planning CT and BOLD-fMRI were performed before radiotherapy, and the language functional areas were delineated based on the fused images of 3D T1 and CT. IMRT technology was used to develop radiotherapy plans with and without language function area protection, naming conventional and protective radiotherapy plans respectively. The maximum radiation dose ( Dmax), average radiation dose ( Dmean), target conformal (CI) and dose uniformity (HI) of PTV of the two plans were compared and analyzed to ensure that the protective radiotherapy plan could meet the radiotherapy standard. Then, the Dmax and Dmean of the language function area were compared and analyzed to evaluate whether the Dmax and Dmean of the language function area were decreased in the protective radiotherapy plan. Results:There were no significant differences in CI, HI, Dmax and Dmean of PTV between the conventional radiotherapy plan and protective radiotherapy plan ( P>0.05). There were statistically significant differences in Dmax and Dmean of Wernicke′s and Broca′s (healthy side and affected side) between the conventional radiotherapy plan and protective radiotherapy plan ( t=3.073-12.707, P<0.05). Dmax and Dmean of Wernicke′s and Broca′s (healthy side and affected side) were decreased in the protective radiotherapy plan compared with the conventional radiotherapy plan, and the decrease was significant in the healthy side. Conclusions:BOLD-fMRI combined with IMRT can not only guarantee the target dose of patients with glioma receiving postoperative radiotherapy, but also reduces the radiation dose to the language function area. Chinese reading task and paragraph comprehension task are the stimulation mode of language function in patients after brain tumor surgery. These tasks are simple and the effect is accurate.
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Introducción: Los gliomas son tumores malignos altamente celulares del sistema ner vioso central. Su grado histológico preoperatorio es de utilidad en el manejo quirúrgico, por lo que la resonancia magnética con secuencias avanzadas intenta brindar mayor información tumoral. Objetivo: Relacionar el coeficiente aparente de difusión (CAD) y celularidad de los gliomas de pacientes entre enero 2015 a diciembre 2017. Metodo logía: Retrospectivamente se obtuvieron de archivos clínicos la edad, sexo, tipo, grado histológico y sitio anatómico. Se calculó el CAD en 5mm 2 en los estudios de resonancia magnética preoperatorias y se utilizó las laminillas para conteo de celularidad en 5mm 2 digitalmente. Se utilizó análisis estadísticos descriptivos y coeficiente de correlación entre CDA con celularidad. Se utilizaron valores de p < 0.05 para significancia estadís tica. Resultados: 46 casos fueron incluidos, 56.5% fueron hombres. El rango de 4164 años fueron los más afectados. El glioblastoma fue el tipo histológico más frecuente (47.8%), así como los gliomas de alto grado (73.9%). El 95.7% fueron supratentoriales. La celularidad promedio fue de 3970 ± 2900 vs 2436 ± 948 núcleos/5mm 2 (p = 0.13), con valores promedio de CDA mínimo de 0.813 x 103 ± 0.229 mm 2 /s vs 1.052 x 103 ± 0.196 mm 2 /s (p = 0.002), para los gliomas de alto y bajo grado respectivamente. La co rrelación entre CDA y celularidad fue débil (R = 0.13, p = 0.37). Conclusión: Existe co rrelación débil inversamente proporcional entre el CDA y la celularidad con distinción de gliomas de bajo y alto grado con valores de CDA mínimos
Introduction: Gliomas are highly cellular malignant tumors of the central nervous sys tem. Its preoperative histological grade is useful in surgical management, so magnetic resonance imaging with advanced sequences tries to provide more tumor information. Objective: Correlate apparent diffusion coefficient (ADC) and cellularity of gliomas of patients between January 2015 to December 2017. Methodology: Data of age, sex, ty pe, histologic grade and anatomic site were retrospectively obtained from clinical archi ves. The preoperative magnetic resonance ADC was calculated in a 5 mm 2 region of interest and the microscope slides were used for the cellularity digitally count in 5 mm 2 . Descriptive statistical analysis and correlation coefficient between ADC and cellularity were used. Values of p <0.05 were used for statistical significance. Results: 46 cases were included, 56.5% were men. The 4164 years ranges were the most affected. Glio blastoma was the most frequent histological type (47.8%), as well as high grade glio mas (73.9%). 95.7% were supratentorial. The average cellularity was 3970 ± 2900 vs 2436 ± 948 nuclei/ 5mm 2 (p = 0.13), with average minimum ADC values of 0.813 x 103 ± 0.229 mm 2 /s vs 1052 x 103 ± 0.196 mm 2 /s (p = 0.002), for high and lowgrade glio mas, respectively. The correlation between ADC and cellularity was weak (R = 0.13, p = 0.37). Conclusions: There is a weak inversely proportional correlation between ADC and cellularity. With distinction of low and highgrade gliomas with minimum ADC values
Subject(s)
Humans , Male , Female , Middle Aged , Astrocytes/pathology , Glioma/epidemiology , Oligodendroglioma/epidemiology , Magnetic Resonance Imaging/methods , Glioblastoma/physiopathologyABSTRACT
To explore the utility of apparent diffusion coefficient(ADC)histogram analysis for differentiating genetic subtypes of diffuse lower-grade gliomas. A total of 55 patients with WHO grade Ⅱ/Ⅲ diffuse lower-grade gliomas who underwent preoperative routine brain magnetic resonance imaging and diffusion weighted imaging in our center were retrospectively evaluated.Among whom there were 14 patients with isocitrate dehydrogenase(IDH)wild-type gliomas(IDH group),19 patients with IDH-mutant 1p19q intact gliomas(IDH 1p19q group),and 22 patients with IDH-mutant 1p19q co-deleted gliomas(IDH 1p19q group).The whole-lesion ADC values derived from histogram analysis(including ADC,ADC,ADC5%,ADC10%,ADC25%,ADC50%,ADC75%,ADC90%,ADC95%,ADC,mode,range,skewness,kurtosis,standard deviation,inhomogeneity,and entrophy)were measured for each patient.All parameters between the different genetic subtypes were compared by using the Student's test or Mann-Whitney test.Receiver operating curve(ROC)analysis was used to assess the diagnostic performance of ADC histogram in distinguishing the different genetic subtypes. Compared with IDH group,the ADC75%(=0.021),ADC90%(=0.015),ADC95%(=0.014),ADC (=0.035),range(=0.009),standard deviation(=0.001)and inhomogeneity(=0.001)were significantly lower in IDH group;in contrast,the ADC (=0.031)and kurtosis(=0.020)of IDH group were significantly higher than those in IDH group.The ADC(=0.010),ADC5%(=0.016),ADC10%(=0.012),ADC25%(=0.007),ADC50%(=0.005),ADC75%(=0.015),and mode(=0.002)were significantly higher in IDH 1p19q group than in IDH 1p19q group.Inhomogeneity achieved the highest area under ROC(AUC)(0.811)in differentiating IDH gliomas and IDH gliomas,with a cutoff value of 0.229;the sensitivity and specificity were 85.7% and 73.2%.The mode achieved the highest AUC(0.744)in differentiating IDH 1p19q gliomas and IDH 1p19q gliomas,with a cutoff value was 1448.75×10 mm /s;the sensitivity and specificity were 57.9% and 90.9%. ADC histograms analysis may be helpful to differentiate genetic subtypes in lower-grade gliomas.
Subject(s)
Humans , Brain Neoplasms , Diffusion Magnetic Resonance Imaging , Glioma , ROC Curve , Retrospective StudiesABSTRACT
La neurofibromatosis (NF) comprende un grupo de enfermedades genéticas de herencia autosómica dominante, que se clasifican de la siguiente manera: neurofibromatosis tipo 1 (NF1), neurofibromatosis tipo 2 (NF2) y schwannomatosis (también conocida como neurofibromatosis tipo 3). Esta última es una enfermedad muy infrecuente, con una prevalencia aproximada de 1/126 000 personas, por lo que solo profundizaremos las dos primeras. La NF1, también conocida como la enfermedad de Von Recklinghausen, es la más frecuente de las tres y afecta principalmente la piel y el sistema nervioso periférico. Se caracteriza por la presencia de máculas "café con leche", pecas axilares o inguinales, nódulos de Lisch (hamartomas en el iris) y neurofibromas (tumores de la vaina de nervios periféricos). Otras manifestaciones menos frecuentes, aunque de mayor gravedad, incluyen gliomas del nervio óptico, meningiomas, neurofibromas malignos, escoliosis y displasia de la tibia. Su diagnóstico se suele realizar al nacimiento o durante los primeros años de vida, y se estima que un 50% de quienes la padecen presenta dificultades cognitivas. No hay datos concluyentes sobre la mortalidad en los pacientes con NF1, aunque se sabe que la expectativa de vida es menor que en la población general. La NF2 tiene una prevalencia considerablemente menor que la NF1 y su inicio es más tardío, afectando principalmente a adultos jóvenes. La presentación clínica típica se caracteriza por acúfenos, hipoacusia y ataxia en contexto de la presencia de schwannomas vestibulares bilaterales. Otros hallazgos menos frecuentes incluyen schwannomas de nervios periféricos, meningiomas, ependimomas o astrocitomas. La esperanza de vida es de unos 36 años, con una supervivencia media desde el momento del diagnóstico de 15 años. (AU)
Neurofibromatosis (NF) includes a group of genetic diseases with an autosomal-dominant inheritance pattern, and they are classified as follows: Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and Schwannomatosis (also known as neurofibromatosis type 3). This last one is a very rare disease, with an approximate prevalence of 1/126000, so we will only deepen in the first two. NF1, also known as von Recklinghausen disease, is the most frequent, and mainly affects the skin and peripheral nervous system. Its typical manifestations are the presence of café-au-lait macules, axillary or inguinal freckles, Lisch nodules (hamartomas in the iris) and neurofibromas (peripheral nerve sheath tumors). Less frequent manifestations, although more serious, include optic nerve gliomas, meningiomas, malignant neurofibromas, scoliosis and tibial dysplasia. The diagnosis is usually made at birth or during the first years of life, and approximately 50% of patients present cognitive difficulties. There is no conclusive data on mortality in patients with NF1, although it is known that life expectancy is lower than in general population. NF2 has a considerably lower prevalence than NF1, and its onset is later in life, mainly affecting young adults. Its typical clinical presentation is characterized by tinnitus, hearing loss and ataxia in the context in the presence of bilateral vestibular schwannomas. Less frequent findings include peripheral nerve schwannomas, meningiomas, ependymomas or astrocytomas. Life expectancy is about 36 years old, with a median survival from the moment of diagnosis of 15 years. (AU)
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Adult , Young Adult , Neurofibromatosis 2/etiology , Neurofibromatosis 1/etiology , Neurofibromatoses/classification , Astrocytoma/physiopathology , Ataxia , Scoliosis/physiopathology , Tibia/abnormalities , Tinnitus , Bone Diseases, Developmental/physiopathology , Neuroma, Acoustic/complications , Life Expectancy , Neurofibromatosis 2/epidemiology , Neurofibromatosis 1/physiopathology , Neurofibromatosis 1/mortality , Neurofibromatosis 1/epidemiology , Neurofibromatoses/diagnosis , Optic Nerve Glioma/physiopathology , Ependymoma/physiopathology , Hearing Loss , Iris Diseases/physiopathology , Melanosis/physiopathology , Meningioma/physiopathology , Neurilemmoma/etiology , Neurilemmoma/physiopathology , Neurofibroma/physiopathology , Neurofibroma/pathologyABSTRACT
Introducción: Nimotuzumab es una inmunoglobina de isotipo IgG1, obtenido por tecnología de ADN recombinante. La expectativa de vida de niños con tumores cerebrales recurrentes, refractarios a tratamientos a la cirugía, la radioterapia y la quimioterapia es de un mes aproximadamente. Con este tratamiento la supervivencia alcanza 44,5 meses. Objetivos: Presentar el caso clínico de un paciente con diagnóstico de Astrocitoma anaplásico que recibió tratamiento oncoespecífico concurrente con Nimotuzumab. Presentación de caso: Se realizó la descripción del diagnóstico, tratamiento y evolución de un paciente de 31 años de edad que fue diagnosticado con una neoplasia del sistema nervioso central. (Astrocitoma anaplásico). Recibió la combinación terapéutica de cirugía, radioterapia y anticuerpos monoclonales, lográndose una sobrevida de 39 meses. Conclusiones: La adición del anticuerpo monoclonal al tratamiento estándar de los tumores cerebrales aumentó la sobrevida del paciente, convirtiéndose en una alternativa terapéutica segura, ventajosa y factible como parte del tratamiento convencional en las condiciones asistenciales(AU)
Introduction: Nimotuzumab is an IgG1 isotype immunoglobin, obtained by recombinant DNA technology. Life expectancy is approximately one month in children with recurrent brain tumors, refractory to treatments to surgery, radiotherapy and chemotherapy. Survival reaches 44.5 months when using Nimotuzumab. Objectives: To report the clinical case of a patient diagnosed with anaplastic astrocytoma who received concurrent oncospecific treatment with Nimotuzumab. Case report: This paper describes the diagnosis, treatment and evolution of a 31-year-old male patient with neoplasm of the central nervous system (Anaplastic astrocytoma). He received the therapeutic combination of surgery, radiotherapy and monoclonal antibodies, achieving a survival of 39 months. Conclusions: The adding the monoclonal antibody to the standard treatment of brain tumors increased patient survival, making it a safe, advantageous and feasible therapeutic alternative as part of conventional treatment in healthcare conditions(AU)
Subject(s)
Humans , Male , Adult , Astrocytoma/surgery , Astrocytoma/diagnosis , Astrocytoma/therapy , Central Nervous System , Reference Drugs , Antibodies, Monoclonal, Humanized/therapeutic use , Survival AnalysisABSTRACT
RESUMEN Introducción: el astrocitoma anaplásico y el glioblastoma multiforme son las formas más agresivas de glioma maligno. Existen avances en radioterapia, quimioterapia y tratamientos de resección quirúrgica agresiva. Esto último incluye métodos como los de tomografía de coherencia óptica, cirugía guiada por fluorescencia, craneotomía de vigilia, terapia térmica intersticial con láser para la ablación por glioblastoma multiforme, microscopía intraoperatoria confocal y espectrometría de masas intraoperatoria, pero a pesar de todo ello el pronóstico resulta sombrío. Objetivo: determinar el comportamiento de los gliomas de alto grado en el Servicio de Neurocirugía de la provincia Matanzas. Materiales y métodos: estudio observacional, descriptivo, transversal, con los pacientes diagnosticados de gliomas de alto grado, en el Servicio Neurocirugía, de la provincia Matanzas, en el período de 1ero de enero del 2017 a 1ero de enero del 2019, para un total de 40 casos. Resultados: la edad media de las lesiones fue de 52 años, la cefalea fue el síntoma predominante, con el 72,2 %. La sintomatología se presentó con una evolución de menos de un mes. Conclusiones: en el 62 % predominaron los gliomas frontales y la variedad histológica glioblastoma multiforme. La excéresis subtotal se aplicó en la mayor cantidad de cirugías, la calidad de vida al egreso fue superior que al ingreso (AU).
ABSTRACT Introduction. Anaplastic astrocytoma (AA) and Glioblastoma multiforme (GBM) are the most aggressive forms of malignant glioma. Despite advances in radiotherapy, chemotherapy and aggressive surgical resection treatments, such as optical coherence tomography, fluorescence-guided surgery, waking craniotomy, laser interstitial thermal therapy for GBM ablation, intraoperative confocal microscopy and intraoperative mass spectrometry, the prognosis remains bleak. Objective: to determine the behavior of high grade gliomas in the Neurosurgery Service of the province of Matanzas. Materials and methods: cross-sectional, descriptive, observational study with patients diagnosed with high-grade gliomas in the Neurosurgery Service of the province of Matanzas, in the period from January 1, 2017 to January 1, 2019, for a total of 40 cases. Results: the average age of the lesionated patients was 52 years; headache was the predominant symptom, with 72.2 %; the evolution at the presentation of symptoms was less than a month. Conclusions: frontal gliomas predominated in 62 % of the cases, and predominated also glioblastoma multiforme histological variety. Subtotal excision was used in most surgeries. Life quality at discharging was higher than at the moment of admission (AU).
Subject(s)
Humans , Glioma/epidemiology , Epidemiology, Descriptive , Cross-Sectional Studies , Observational Study , Glioma/surgery , Glioma/diagnosis , NeurosurgeryABSTRACT
Adjuvant temozolomide-based chemotherapy has become the standard of care for most postoperative glioma patients. However, a large proportion of these patients do not respond to temozolomide. DNA repair enzyme O6-methylguanine-DNA methyl-transferase (MGMT) promoter methylation has emerged as an important molecular marker in patients with gliomas. It is associated with prognosis and resistance to alkylated drugs such as temozolomide. MGMT promoter methylation is the key mechanism of MGMT gene silencing, thereby inhibiting DNA repair and increasing the sensitivity of chemotherapy. We reviewed current data on the prog-nostic and predictive relevance of MGMT testing and clinical trials, summarized the clinical application of MGMT promoter methyla-tion, in order to provide reference for the individualized treatment of glioma patients.
ABSTRACT
Objective To explore the MRI findings of diffuse midline gliomas with H3K27M mutation, and help us understand this new entity and improve the accuracy of diagnosis. Methods The clinical and imaging data of 17 diffuse midline gliomas with H3K27M mutation confirmed by pathology were retrospectively collected from July 2016 to April 2018 in Guangdong Sanjiu Brain Hospital. All patients were performed with pre?contrast and post?contrast MRI examination. All images were analyzed according to the location, shape, boundary, solid or cystic, signal feature, enhancement feature, and degree of edema. Results (1) Location:Six cases located in thalamus,4 cases located in brainstem,1 located in hypothalamus, 6 cases had multiple lesions in the midline and/or involving one or more brain. (2) Morphology and boundary:Seven cases had regular shape and clear boundary, 10 cases had irregular shapes and unclear boundaries. (3) Necrosis, cystic degeneration, hemorrhage: Twelve cases had necrosis or cystic degeneration in varying degree, 4 cases had hemorrhage. (4) Signal and enhancement features: The solid component showed slightly?low or low signal on T1WI, and slightly?high or high signal on T2WI; the cystic component showed obvious low signal on T1WI and obvious high signal on T2WI. T1WI enhancement:Eight cases showed uneven light?moderate enhancements, and all cases were adults; Six cases showed significant enhancements with large or small rings; Three cases showed uneven obvious enhancement. (5) Peritumoral edema: Fourteen cases had mild peritumoral edema,1 case had moderate peritumoral edema,2 cases had obvious peritumoral edema. Conclusion The MRI findings of diffuse midline gliomas with H3K27M mutation had certain characteristics,which can help to improve the level of diagnosis and differential diagnosis.