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1.
MedUNAB ; 24(3): 359-364, 202112.
Article in Spanish | LILACS | ID: biblio-1353578

ABSTRACT

Introducción. El xantoastrocitoma pleomórfico es una lesión glial de bajo grado de malignidad (grado II), puede presentar transformación maligna progresando a xantoastrocitoma pleomórfico anaplásico o glioblastoma multiforme, clasificados en grado III y IV, respectivamente, de acuerdo con la OMS. El glioblastoma epitelioide es un subtipo morfológico poco común del glioblastoma, de comportamiento agresivo, asociado a recurrencia temprana y compromiso leptomeníngeo. Presentación del caso. Se describe un reporte de caso de paciente femenina de 13 años con hallazgos de xantoastrocitoma pleomórfico anaplásico asociado a glioblastoma epitelioide, neoplasia poco frecuente que suele presentarse en la población pediátrica y en los adultos jóvenes. Discusión. El diagnóstico de glioblastoma epitelioide constituye un desafío, solo se han reportado unas pocas series pequeñas en la población adulta y pediátrica. Conclusión. Los hallazgos imagenológicos en las dos entidades son similares y comparten características histopatológicas e incluso algunos hallazgos moleculares superpuestos, lo cual dificulta su diferenciación, por lo que continúa siendo de gran controversia si se presentan conjuntamente o si el xantoastrocitoma pleomórfico anaplásico es un precursor del glioblastoma epitelioide.


Introduction. Pleomorphic xanthoastrocytoma is a glial lesion with low grade of malignancy (grade II), it can present malignant transformation progressing to anaplastic pleomorphic xanthoastrocytoma or glioblastoma multiforme, classified as grade III and IV, respectively, according to the WHO. Epithelioid glioblastoma is a rare morphological subtype of glioblastoma, with aggressive behavior, associated with early recurrence and leptomeningeal compromise. Case Presentation. Case report of a 13-year-old female patient with findings of anaplastic pleomorphic xanthoastrocytoma associated with epithelioid glioblastoma, a rare neoplasm that usually occurs in the pediatric population and in young adults. Discussion. The diagnosis of epithelioid glioblastoma is challenging, only a few small series have been reported in the adult and pediatric population. Conclusion. The imaging findings in the two entities are similar and share histopathological characteristics and even some overlapping molecular findings, which makes their differentiation difficult. For this reason, there is still a great controversy whether these entities are present continuously or whether the anaplastic pleomorphic xanthoastrocytoma is a precursor of epithelioid glioblastoma.


Introdução. O xantoastrocitoma pleomórfico é uma lesão glial de baixo grau de malignidade (grau II), pode apresentar transformação maligna progredindo para xantoastrocitoma pleomórfico anaplásico ou glioblastoma multiforme, classificados como grau III e IV, respectivamente, de acordo com a OMS. O glioblastoma epitelióide é um subtipo morfológico raro de glioblastoma, com comportamento agressivo, associado a recorrência precoce e envolvimento leptomeníngeo. Apresentação do caso. É descrito um relatório de caso de uma paciente feminina de 13 anos com achados de xantoastrocitoma pleomórfico anaplásico associado ao glioblastoma epitelióide, uma neoplasia rara que geralmente ocorre na população pediátrica e em adultos jovens. Discussão. O diagnóstico do glioblastoma epitélioide é desafiador, apenas algumas pequenas séries foram reportadas na população adulta e pediátrica. Conclusão. As descobertas imagiológicas nas duas entidades são semelhantes e compartilham características histopatológicas e, até mesmo, algumas descobertas moleculares sobrepostas, o que dificulta sua diferenciação, portanto permanece controverso se ocorrem juntas ou se o xantoastrocitoma pleomórfico anaplásico é um precursor do glioblastoma epitélioide.


Subject(s)
Brain Neoplasms , Astrocytoma , Glioblastoma , Diagnosis, Differential , Glioma
2.
Medicina (B.Aires) ; 81(5): 791-799, oct. 2021. graf
Article in Spanish | LILACS | ID: biblio-1351053

ABSTRACT

Resumen La mutación puntual V600E del gen BRAF juega un papel fundamental en la tumorigénesis de muchos gliomas. La inhibición de su producto forma parte de terapias innovadoras emergentes en los últimos años. Conocer el rol de estos tratamientos resulta imprescindible. El objetivo del trabajo fue describir la respuesta clínico-radiológica en niños con gliomas BRAF V600E mutado tratados con inhibidores BRAF. Para ello se realizó un estudio descriptivo y retrospectivo en pacientes menores de 16 años con gliomas BRAF V600E mu tado que recibieron vemurafenib o dabrafenib en el Hospital Garrahan. Trece pacientes tratados en los últimos 7 años fueron incluidos: 9 gliomas de bajo grado y 4 de alto grado. La mediana de edad al diagnóstico fue 8.6 años (0.89-14.04) y del comienzo del inhibidor 11.62 años (3.64-15.42). Inicialmente, todos habían realizado tratamiento quirúrgico, y 12/13 recibieron previamente otra terapia: 11 quimioterapia (eventualmente hasta 4 líneas distintas) y 4 radioterapia. Con la terapia dirigida, 10 pacientes tuvieron una disminución tumoral mayor o igual al 25%, quedando evidenciada en 7 niños la mejor respuesta dentro de los 6 meses del inicio. Hubo 4 progresados intratratamiento (todos alto grado), y 2 progresados prontamente luego de suspender el inhibidor (ambos bajo grado). Cinco presentaron efectos adversos grado 3-4, con recuperación ad-integrum. Se describe una buena y sostenida respuesta clínico-radiológica, con tolerancia aceptable, en pacientes con gliomas de bajo grado BRAF V600E mutado tratados con inhibidores BRAF V600E . En contraste, la respuesta en pacientes con gliomas de alto grado fue intermedia y de poca duración, con progresión tumoral precoz.


Abstract The BRAF V600E point mutation plays a key role in the tumorigenesis of many gliomas. Inhibiting its product is part of the innovative therapies emerging in recent years. Knowing the role of these treatments is essential. The aim of this experience was to describe the clinical-radiological response of pediatric BRAF V600E mutated gliomas treated with BRAF inhibitors. To this end, a descriptive and retrospective study was performed in patients under 16 years of age with BRAF V600E gliomas, who received vemurafenib or dabrafenib at Hospital Garrahan. Thirteen patients treated in the last 7 years were included: 9 were low-grade and 4 high-grade gliomas. The median age at diagnosis was 8.6 years (0.89-14.04) and at start of targeted therapy was 11.62 years (3.64-15.42). All patients had previously a surgical procedure, and 12/13 had received another therapy prior BRAF inhibition: 11 chemotherapy (in one case, up to 4 different protocols) and 4 radiotherapy. Under targeted therapy, tumour response was obtained in 10 patients (size reduction equal to or greater than 25%), and best response was observed in the first 6 months of treatment in 7 children. Four patients progressed under treatment (all high-grade gliomas) and 2 progressed shortly after stopping the inhibitor (both low-grade gliomas). Five patients had grade 3-4 toxicity, with subsequent full recovery. A good and sustained clinical-radiological response, with acceptable tolerance, is described in patients with BRAF V600E mutated low-grade gliomas treated with BRAF V600E inhibitors. In contrast, the response in patients with high-grade gliomas was intermediate and of short duration, with early tumour progression.


Subject(s)
Humans , Child , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Proto-Oncogene Proteins B-raf/genetics , Glioma/genetics , Glioma/drug therapy , Retrospective Studies , Hospitals , Mutation
3.
Rev. argent. radiol ; 85(1): 3-10, ene. 2021. tab, graf
Article in Spanish | LILACS | ID: biblio-1155707

ABSTRACT

Resumen Objetivo: Analizar características por resonancia magnética (RM) de gliomas IDH-mutados (grado II y III) en base a parámetros cualitativos, a fin de valorar el rendimiento del signo del mismatch T2-FLAIR y otras características morfológicas de los tumores, en predecir el estado del 1p/19q y su reproducibilidad interobservador. Métodos Estudio retrospectivo, descriptivo y analítico sobre una cohorte de 53 gliomas IDH-mutados (grado II y III) y molecularmente definidos respecto al 1p/19q, seleccionados a partir de la base de datos de la institución, durante el periodo 2014- 2019. Dos neuroradiólogos evaluaron características imagenológicas de forma independiente y enmascarada al diagnóstico: mismatch T2-FLAIR, localización tumoral, bordes, señal, infiltración cortical e inhomogeneidad en T2. Los casos discordantes fueron evaluados por un tercer neuroradiólogo de mayor experiencia. Resultados: Treinta de 53 (56,6%) gliomas fueron no codelecionados, y 23/53 (43,4%) codelecionados. El signo del mismatch T2-FLAIR fue positivo en 16/53 (30,18%) pacientes, 15/16 (93,75%) no codelecionados y 1/16 (6,25%) codelecionado (Exacto de Fisher p = <,0001). Los dos evaluadores demostraron una concordancia interobservador casi perfecta para ese signo, κ =,907 (95% CI, 0,781 a 1,0). La especificidad y el valor predictivo positivo del signo para predecir la ausencia de la codeleción fue de un 95,7% y un 93,8% respectivamente. Discusión: La reciente actualización en la clasificación de los gliomas los clasifica acorde a su perfil molecular. En los últimos años, varios investigadores han estudiado características morfológicas por RM de los tumores con la intención de predecir las características moleculares de los mismos. Conclusión: En nuestra población, el signo del mismatch T2-FLAIR es el único biomarcador radiológico que muestra asociación estadísticamente significativa en predecir la ausencia de codeleción en los gliomas IDH-mutados (grado II y III), con una alta especificidad y un alto valor predictivo positivo.


Abstract Objective: To analyze magnetic resonance (MR) characteristics of IDH-mutated gliomas (grades II/III) utilizing qualitative parameters with the goal of assessing the performance of the T2-FLAIR mismatch sign and other morphological characteristics of tumors in predicting the 1p/19q co-deletion status as well as inter-observer reproducibility. Methods: Retrospective and descriptive study analyzing a cohort of 53 IDH-mutated lower-grade (grades II/III) gliomas with known 1p/19q co-deletion status. Patients meeting selection criteria for this study were taken from our institutional data from 2014-2019. Two neuroradiologists assessed the following imaging characteristics independently, and blinded from the diagnosis: T2-FLAIR mismatch, tumor location, borders, signal characteristics, cortical infiltration and T2* inhomogeneity. In the event of discordant interpretations, a third senior neuroradiologist also evaluated the case. Results: 23 of the 53 (43.4%) gliomas demonstrated 1p/19q co-deletion and 30 of 53 (56.6%) did not. T2-FLAIR mismatch was positive in 16 of 53 cases (30.2%) with 15 of 16 (93.8%) demonstrating no co-deletion and 1/16 (6.25%) with co-deletion (Fisher's exact p = < .0001). The two readers showed an almost perfect interreader agreement for this sign κ = 0.907 (95% CI, 0.781 to 1.0). Specificity and positive predictive value of the sign to predict the absence of co-deletion was 95.7% and 93.8% respectively. Discussion: The recent update in classification of lower-grade gliomas segregates gliomas according to molecular profile. In the recent past, many researchers have studied MR morphologic characteristics of these tumors with the intention of predicting molecular features of said tumors Conclusion: In our patient population, T2-FLAIR mismatch sign is the only radiologic biomarker that shows statistically significant association with the absence of 1p/19q co-deletion in lower-grade gliomas, with high specificity and positive predictive value.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Brain Neoplasms/diagnostic imaging , Biomarkers , Glioma/diagnostic imaging , Oligodendroglioma/diagnostic imaging , Astrocytoma/diagnostic imaging , Magnetic Resonance Spectroscopy , Epidemiology, Descriptive , Retrospective Studies , Glioma/classification
4.
Frontiers of Medicine ; (4): 551-561, 2021.
Article in English | WPRIM | ID: wpr-888745

ABSTRACT

Glioma is the most common lethal tumor of the human brain. The median survival of patients with primary World Health Organization grade IV glioma is only 14.6 months. The World Health Organization classification of tumors of the central nervous system categorized gliomas into lower-grade gliomas and glioblastomas. Unlike primary glioblastoma that usually develop de novo in the elderly, secondary glioblastoma enriched with an isocitrate dehydrogenase mutant typically progresses from lower-grade glioma within 5-10 years from the time of diagnosis. Based on various evolutional trajectories brought on by clonal and subclonal alterations, the evolution patterns of glioma vary according to different theories. Some important features distinguish the normal brain from other tissues, e.g., the composition of the microenvironment around the tumor cells, the presence of the blood-brain barrier, and others. The underlying mechanism of glioma recurrence and evolution patterns of glioma are different from those of other types of cancer. Several studies correlated tumor recurrence with tumor heterogeneity and the immune microenvironment. However, the detailed reasons for the progression and recurrence of glioma remain controversial. In this review, we introduce the different mechanisms involved in glioma progression, including tumor heterogeneity, the tumor microenvironment and drug resistance, and their pre-clinical implements in clinical trials. This review aimed to provide new insights into further clinical strategies for the treatment of patients with recurrent and secondary glioma.


Subject(s)
Aged , Brain Neoplasms/genetics , Drug Resistance , Glioblastoma , Glioma/genetics , Humans , Mutation , Neoplasm Recurrence, Local/drug therapy , Tumor Microenvironment
5.
Journal of Biomedical Engineering ; (6): 1062-1071, 2021.
Article in Chinese | WPRIM | ID: wpr-921846

ABSTRACT

Glioma is the most common malignant brain tumor and classification of low grade glioma (LGG) and high grade glioma (HGG) is an important reference of making decisions on patient treatment options and prognosis. This work is largely done manually by pathologist based on an examination of whole slide image (WSI), which is arduous and heavily dependent on doctors' experience. In the World Health Organization (WHO) criteria, grade of glioma is closely related to hypercellularity, nuclear atypia and necrosis. Inspired by this, this paper designed and extracted cell density and atypia features to classify LGG and HGG. First, regions of interest (ROI) were located by analyzing cell density and global density features were extracted as well. Second, local density and atypia features were extracted in ROI. Third, balanced support vector machine (SVM) classifier was trained and tested using 10 selected features. The area under the curve (AUC) and accuracy (ACC) of 5-fold cross validation were 0.92 ± 0.01 and 0.82 ± 0.01 respectively. The results demonstrate that the proposed method of locating ROI is effective and the designed features of density and atypia can be used to predict glioma grade accurately, which can provide reliable basis for clinical diagnosis.


Subject(s)
Brain Neoplasms/diagnostic imaging , Glioma/diagnostic imaging , Humans , Magnetic Resonance Imaging , Neoplasm Grading , Support Vector Machine
6.
Chinese Medical Journal ; (24): 2535-2543, 2021.
Article in English | WPRIM | ID: wpr-921208

ABSTRACT

BACKGROUND@#It is crucial to differentiate accurately glioma recurrence and pseudoprogression which have entirely different prognosis and require different treatment strategies. This study aimed to assess the diagnostic accuracy of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as a tool for distinguishing glioma recurrence and pseudoprogression.@*METHODS@#According to particular criteria of inclusion and exclusion, related studies up to May 1, 2019, were thoroughly searched from several databases including PubMed, Embase, Cochrane Library, and Chinese biomedical databases. The quality assessment of diagnostic accuracy studies was applied to evaluate the quality of the included studies. By using the "mada" package in R, the heterogeneity, overall sensitivity, specificity, and diagnostic odds ratio were calculated. Moreover, funnel plots were used to visualize and estimate the publication bias in this study. The area under the summary receiver operating characteristic (SROC) curve was computed to display the diagnostic efficiency of DCE-MRI.@*RESULTS@#In the present meta-analysis, a total of 11 studies covering 616 patients were included. The results showed that the pooled sensitivity, specificity, and diagnostic odds ratio were 0.792 (95% confidence interval [CI] 0.707-0.857), 0.779 (95% CI 0.715-0.832), and 16.219 (97.5% CI 9.123-28.833), respectively. The value of the area under the SROC curve was 0.846. In addition, the SROC curve showed high sensitivities (>0.6) and low false positive rates (<0.5) from most of the included studies, which suggest that the results of our study were reliable. Furthermore, the funnel plot suggested the existence of publication bias.@*CONCLUSIONS@#While the DCE-MRI is not the perfect diagnostic tool for distinguishing glioma recurrence and pseudoprogression, it was capable of improving diagnostic accuracy. Hence, further investigations combining DCE-MRI with other imaging modalities are required to establish an efficient diagnostic method for glioma patients.


Subject(s)
Glioma/diagnostic imaging , Humans , Magnetic Resonance Imaging , Neoplasm Recurrence, Local/diagnostic imaging , ROC Curve , Sensitivity and Specificity
7.
Chinese Medical Journal ; (24): 2398-2402, 2021.
Article in English | WPRIM | ID: wpr-921130

ABSTRACT

The demand for acquiring different languages has increased with increasing globalization. However, knowledge of the modification of the new language in the neural language network remains insufficient. Although many details of language function have been detected based on the awake intra-operative mapping results, the language neural network of the bilingual or multilingual remains unclear, which raises difficulties in clinical practice to preserve patients' full language ability in neurosurgery. In this review, we present a summary of the current findings regarding the structure of the language network and its evolution as the number of acquired languages increased in glioma patients. We then discuss a new insight into the awake intra-operative mapping protocol to reduce surgical risks during the preservation of language function in multilingual patients with glioma.


Subject(s)
Brain Mapping , Brain Neoplasms/surgery , Glioma/surgery , Humans , Language , Multilingualism
8.
Article in Chinese | WPRIM | ID: wpr-880829

ABSTRACT

OBJECTIVE@#To establish a mouse model bearing orthotopic temozolomide (TMZ)-resistant glioma that mimics the development of drug resistance in gliomas @*METHODS@#Seventy-eight adult C57BL/6 mice were randomly divided into 6 groups (@*RESULTS@#The mouse models bearing TMZresistant glioma was successfully established. The cells from the high-dose induced group showed a significantly higher colony-forming rate than those from the high-dose control group (@*CONCLUSIONS@#Progressive increase of TMZ doses in mice bearing orthotopic gliomas can effectively induce TMZ resistance of the gliomas.


Subject(s)
Animals , Antineoplastic Agents, Alkylating/pharmacology , Brain Neoplasms/drug therapy , Cell Line, Tumor , Disease Models, Animal , Drug Resistance, Neoplasm , Glioma/drug therapy , Mice , Mice, Inbred C57BL , Temozolomide/therapeutic use
9.
Article in English | WPRIM | ID: wpr-880671

ABSTRACT

OBJECTIVES@#Glioma is the most common intracranial primary tumor in central nervous system. Glioma grading possesses important guiding significance for the selection of clinical treatment and follow-up plan, and the assessment of prognosis. This study aims to explore the feasibility of logistic regression model based on radiomics to predict glioma grading.@*METHODS@#Retrospective analysis was performed on 146 glioma patients with confirmed pathological diagnosis from January, 2012 to December, 2018. A total of 41 radiomics features were extracted from contrast-enhanced T@*RESULTS@#A total of 5 imaging features selected by LASSO were used to establish a logistic regression model for predicting glioma grading. The model showed good discrimination with AUC value of 0.919. Hosmer-Lemeshow test showed no significant difference between the calibration curve and the ideal curve (@*CONCLUSIONS@#The logistic regression model using radiomics exhibits a relatively high accuracy for predicting glioma grading, which may serve as a complementary tool for preoperative prediction of giloma grading.


Subject(s)
Brain Neoplasms/diagnostic imaging , Glioma/diagnostic imaging , Humans , Logistic Models , Magnetic Resonance Imaging , ROC Curve , Retrospective Studies
10.
Article in English | WPRIM | ID: wpr-880617

ABSTRACT

OBJECTIVES@#To investigate the effects of propofol on the proliferation and invasion of glioma U87 cells and to explore the possible anti-tumor mechanisms.@*METHODS@#The glioma U87 cells was divided into a blank group, a positive control group, and the propofol groups (1.00, 2.00 or 5.00 mmol/L). Cell counting kit-8 (CCK-8) was used to detect cell proliferation; Transwell method was used to detect the effect of propofol on invasion and migration of U87 cells; real-time PCR was used to detect the expression of microRNA-134 (miR-134); Western blotting was used to detect the expression levels of reproduction-related protein Ki-67, invasion-related protein metalloproteinase-2 (MMP-2), metalloproteinase-9 (MMP-9) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway-related protein.@*RESULTS@#Compared with the blank group, the proliferation, invasion and migration capacity of U87 cells were reduced in the positive control group and the propofol groups after 48 hours (all @*CONCLUSIONS@#Propofol can decrease the proliferation rate, and the invasion and migration abilities of U87 cells, which may be achieved by up-regulation of miR-134 and suppression of PI3K/Akt signaling pathway.


Subject(s)
Cell Line, Tumor , Cell Movement , Cell Proliferation , Glioma/genetics , Humans , Matrix Metalloproteinase 2/genetics , MicroRNAs/genetics , Phosphatidylinositol 3-Kinases/genetics , Propofol/pharmacology , Proto-Oncogene Proteins c-akt/genetics
11.
Braz. j. med. biol. res ; 54(7): e10236, 2021. graf
Article in English | LILACS | ID: biblio-1249317

ABSTRACT

This work aimed to research the function of MARVEL domain-containing protein 1 (MARVELD1) in glioma as well as its functioning mode. Bioinformatics analysis was utilized to assess the MARVELD1 expression in glioma tissues and its relationship with grade and prognosis, based on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Chinese Glioma Genome Atlas (CGGA) databases. Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assays were carried out to determine the impact of MARVELD1 on malignant biological behavior of glioma, such as proliferation, invasion, and migration. qRT-PCR was carried out to test the mRNA level of MARVELD1. Western blot assay was performed to measure the protein expression of MARVELD1 and JAK/STAT pathway-related proteins. MARVELD1 was expressed at high levels in glioma tissues and cell lines. Kaplan-Meier survival analysis revealed that the higher MARVELD1 expression, the shorter the survival time of patients with glioma. Also, the MARVELD1 expression in WHO IV was significantly enhanced compared to that in WHO II and WHO III. Furthermore, the functional analysis of MARVELD1 in vitro revealed that knockdown of MARVELD1 in U251 cells restrained cell proliferation, migration, and invasion, while up-regulation of MARVELD1 in U87 cells presented opposite outcomes. Finally, we found that JAK/STAT signaling pathway mediated the function of MARVELD1 in glioma. MARVELD1 contributed to promoting the malignant progression of glioma, which is the key driver of activation of JAK/STAT signaling pathway in gliomas.


Subject(s)
Humans , Animals , Rats , Brain Neoplasms , Glioma , Phenotype , Signal Transduction , Gene Expression Regulation, Neoplastic , Up-Regulation , Cell Movement , Cell Line, Tumor , Cell Proliferation , MARVEL Domain-Containing Proteins , Membrane Proteins , Mice, Nude , Microtubule-Associated Proteins
12.
Braz. j. med. biol. res ; 54(10): e10653, 2021. tab, graf
Article in English | LILACS | ID: biblio-1285657

ABSTRACT

Vasculogenic mimicry (VM) plays an important role in human glioma progression and resistance to antiangiogenic therapy as a compensatory neovascularization mechanism in malignant tumors. Caveolin-1 (Cav-1) has been found to contribute to VM formation. However, it remains largely unknown whether Cav-1 expression correlates with VM in glioma. In this study, we examined CAV-1 expression levels and VM in human glioma cell lines and in 94 human gliomas with different grades of malignancy, and present Cox proportional hazards regression. The molecular role of Cav-1 in glioma cells was investigated using quantitative polymerase chain reaction (qRT-PCR) assays, western blotting, CCK-8 assays, and tubule formation assays. Cav-1 expression and VM formation were positively correlated with each other and both were closely associated with glioma development and progression as evidenced by the presence of cystic tumor, shortened survival time, and advanced-stage glioma in glioma patients with Cav-1 overexpression/increased VM formation. Cav-1 promoted U251 glioma cell proliferation and VM formation in a Matrigel-based 3D culture model. VM-associated factors including hypoxia-inducible factor 1α (HIF-1α) and p-Akt was significantly elevated by Cav-1 overexpression but suppressed by siCav-1 in U251 cells. Collectively, our study identified Cav-1 as an important regulator of glioma cell proliferation and VM formation, contributing to glioma development and progression.


Subject(s)
Humans , Caveolin 1/genetics , Glioma , Cell Line, Tumor , Cell Proliferation , Neovascularization, Pathologic
13.
Article in Portuguese | LILACS | ID: biblio-1354573

ABSTRACT

Introdução: Os gliomas representam 80% dos tumores do sistema nervoso central. A Organização Mundial da Saúde (OMS) adicionou, em 2016, critérios moleculares na classificação dos gliomas. A fisiopatologia e os fatores de risco desses tumores ainda não são totalmente conhecidos. Objetivo: Realizar uma análise retrospectiva dos laudos anatomopatológicos e imuno-histoquímicos de gliomas. Método: Estudo transversal, retrospectivo e descritivo, a partir de exames anatomopatológicos e imuno-histoquímicos realizados entre janeiro de 2014 e dezembro de 2018 em um laboratório de anatomia patológica na cidade de Maringá-PR. Dos 234 laudos relacionados com o termo glioma, 204 foram selecionados para este estudo. Resultados: Foram encontrados tumores astrocitários, ependimários e oligodendrogliais, sendo que os astrocitomas corresponderam à maioria (86,8% dos casos encontrados). A média de idade ao diagnóstico foi de 51,8 anos e houve maior prevalência desses tumores no sexo masculino. Também foram analisadas mutações detectáveis por imuno-histoquímica como p53 (mutada em 66,7% dos testados), isocitrato desidrogenase (IDH) (28,6% mutados), X-linked alpha-thalassemia mental retardation (ATRX) (21,0%) e marcadores diagnósticos como o epithelial membrane antigen (EMA) positivo em todos os ependimomas analisados. Conclusão: É inegável a necessidade de novas pesquisas sobre os gliomas tanto no campo epidemiológico, tendo em vista a nova classificação, quanto no escopo fisiopatológico e clínico, com o objetivo de melhorar o entendimento sobre a patologia e o tratamento dos pacientes


Introduction: Gliomas represent 80% of the central nervous system tumors. World Health Organization (WHO) has added, in 2016, molecular features to the classification of gliomas. The pathophysiology and risk factors of these tumors are not yet fully understood. Objective: Perform a retrospective analysis of immunohistochemical and anatomopathological reports of gliomas. Method: Cross-sectional, retrospective and descriptive study carried out from anatomopathological and immunohistochemical exams made between January 2014 and December 2018 in a pathological anatomy laboratory in the city of Maringá-PR. Of the 234 reports related to the term glioma, 204 were selected for this study. Results: Astrocytic, ependymal and oligodendroglial tumors were found, with astrocytomas accounting for the majority (86.8% of the cases found). Mean age at diagnosis was 51.8 years and the prevalence was higher in men. Furthermore, immunohistochemically detectable mutations were analyzed, such as p53 (mutated in 66.7% of those tested), isocitrate dehydrogenase (IDH) (28.6% mutated), X-linked alpha-thalassemia mental retardation (ATRX) (21.0%) and diagnostic markers such as positive epithelial membrane antigen (EMA) in all analyzed ependymomas. Conclusion: The necessity of further researches on gliomas is undeniable , both epidemiologically considering the new classification and within the clinical and pathophysiological scope in order to improve the understanding of the pathology and the treatment for the patients


Introducción: Los gliomas representan 80% de los tumores del sistema nervioso central. La Organización Mundial de la Salud (OMS) agregó, en 2016, criterios moleculares sobre como clasificar los gliomas. La fisiopatología y los factores de riesgo de estos tumores aún no se comprenden completamente. Objetivo: Realizar un análisis retrospectivo de informes inmunohistoquímicos y anatomopatológicos de gliomas. Método: Estudio transversal, retrospectivo y descriptivo con base em pruebas anatomopatológicas e inmunohistoquímicas realizadas entre enero de 2014 y diciembre de 2018 en un laboratorio de anatomía patológica de la ciudad de Maringá-PR. De los 234 informes relacionados con el término glioma, se seleccionaron 204 para este estudio. Resultados: Se encontraron tumores astrocíticos, ependimarios y oligodendrogliales, siendo los astrocitomas la mayoría (86,8% de los casos encontrados). La edad media al diagnóstico fue de 51,8 años y hubo una mayor prevalencia de estos tumores en el sexo masculino. También se analizaron mutaciones detectables inmunohistoquímicamente, como p53 (mutado en 66,7% de los analizados), isocitrato desidrogenase(IDH) (28,6% mutado), X-linked alpha-thalassemia mental retardation (ATRX) (21,0%) y marcadores de diagnóstico como epithelial membrane antigen (EMA) positivo en todos los ependimomas analizados. Conclusión: Es innegable la necesidad de profundizaren las investigaciones sobre los gliomas, tanto en el campo epidemiológico, ante la nueva clasificación, como en el ámbito fisiopatológico y clínico, con el objetivo de mejorar el conocimiento sobre la patología y el tratamiento de los pacientes


Subject(s)
Humans , Male , Female , Astrocytoma , Immunohistochemistry , Molecular Epidemiology , Glioblastoma , Glioma , Glioma/classification , Glioma/immunology
14.
Rev. Col. Bras. Cir ; 48: e20202722, 2021. graf
Article in English | LILACS | ID: biblio-1250705

ABSTRACT

ABSTRACT The anesthesia for awake craniotomy (AC) is a consecrated anesthetic technique that has been perfected over the years. Initially used to map epileptic foci, it later became the standard technique for the removal of glial neoplasms in eloquent brain areas. We present an AC anesthesia technique consisting of three primordial times, called awake-asleep-awake, and their respective particularities, as well as delve into the anesthetic medications used. Its use in patients with low and high-grade gliomas was favorable for the resection of tumors within the functional boundaries of patients, with shorter hospital stay and lower direct costs. The present study aims to systematize the technique based on the experience of the largest philanthropic hospital in Latin America and discusses the most relevant aspects that have consolidated this technique as the most appropriate in the surgery of gliomas in eloquent areas.


RESUMO A anestesia para craniotomia em paciente acordado (CPA ou awake craniotomy) é técnica anestésica consagrada e aperfeiçoada ao longo dos últimos anos. Utilizada inicialmente para mapeamento de focos epilépticos, consolidou-se posteriormente como técnica padrão para a remoção de neoplasias de origem glial em áreas eloquentes cerebrais. A técnica de anestesia CPA apresentada constitui-se em três tempos primordiais denominados acordado-dormindo-acordado (asleep-awake-asleep) e respectivas particularidades, assim como o manejo quanto às medicações anestésicas utilizadas de forma pormenorizada. A utilização em gliomas de baixo e de alto grau se demonstrou favorável para a ressecção de tumores dentro dos limites funcionais dos pacientes, com menor tempo de internação hospitalar e de custos diretos. O presente estudo visa realizar a sistematização da técnica baseada na experiência do maior Hospital Filantrópico da América Latina e discute os aspectos mais relevantes que consolidaram essa técnica como a mais adequada na cirurgia dos gliomas em áreas eloquentes.


Subject(s)
Humans , Brain Neoplasms/surgery , Glioma/surgery , Anesthesia , Wakefulness , Craniotomy
15.
Med. lab ; 25(4): 709-719, 2021. ilus, Tabs
Article in Spanish | LILACS | ID: biblio-1370842

ABSTRACT

Introducción. Los gliomas son las neoplasias malignas primarias más frecuentes del sistema nervioso central, asociadas con una mortalidad y morbilidad elevadas. Las mutaciones en los genes IDH1 e IDH2 de la enzima isocitrato deshidrogenasa (IDH) son clave en la tumorogénesis, y son consideradas un factor pronóstico importante en estas neoplasias. En este estudio se buscó determinar la presencia de mutaciones de los genes IDH1 e IDH2 en pacientes con diagnóstico de glioma difuso en diferentes grados, y su correlación con la sobrevida. Metodología. Se realizó un estudio descriptivo, prospectivo y retrospectivo. La población de estudio fueron pacientes entre los 18 y 45 años con diagnóstico de glioma difuso grado II, III y IV, atendidos en el Hospital San Vicente Fundación de Medellín, entre 2012 y 2017, en quienes se realizó un análisis de mutaciones en los genes IDH1 e IDH2 por secuenciación Sanger y tinción de inmunohistoquímica. Resultados. Se incluyeron 14 pacientes con edad promedio de 37 años, 57% de sexo masculino. Glioblastoma fue la neoplasia más frecuente, diagnosticada en el 42,9% de casos. Por inmunohistoquímica, 10 de los 14 (71,4%) pacientes presentaron mutación de la enzima IDH1, en tanto que 1 de los 11 (9%) pacientes en quienes se logró la secuenciación del gen IDH2, mostró mutación. En general, el 78,6% presentó mutaciones de la enzima IDH, con promedio de sobrevida de 48 meses. Conclusión. Estos hallazgos sugieren que los gliomas son un grupo heterogéneo de tumores, con gran variabilidad genética que impacta en su pronóstico y comportamiento


Introduction. Gliomas are the most common primary malignancies of the central nervous system, associated with high mortality and morbidity. Mutations in the isocitrate dehydrogenase (IDH) enzyme IDH1 and IDH2 genes, are key in tumorigenesis, and are considered an important prognostic factor in these neoplasms. This study aimed to determine the presence of IDH1 and IDH2 gene mutations in patients diagnosed with diffuse glioma in different degrees, and their correlation with survival. Methodology. A descriptive, prospective and retrospective study was conducted. The study population consisted of patients between the ages of 18 and 45 with a diagnosis of grade II, III and IV diffuse glioma, treated at the Hospital San Vicente Fundación in Medellín, between 2012 and 2017, in whom an analysis of IDH1 and IDH2 gene mutations was performed by Sanger sequencing and immunohistochemical staining. Results. Fourteen patients with a mean age of 37 years were included, 57% were male. Glioblastoma was the most frequent neoplasm, diagnosed in 42.9% of the cases. By immunohistochemistry, 10 of the 14 (71.4%) patients had a mutation of the IDH1 enzyme, while 1 of the 11 (9%) patients in whom IDH2 gene sequencing was achieved showed a mutation. In general, 78.6% had IDH enzyme mutations, with an average survival of 48 months. Conclusion. These findings suggest that gliomas are a heterogeneous group of tumors, withgreat genetic variability that impacts their prognosis and behavior


Subject(s)
Isocitrate Dehydrogenase , Oligodendroglioma , Astrocytoma , Immunohistochemistry , Sequence Analysis, DNA , Glioblastoma , Glioma , Mutation
16.
Rev. argent. neurocir ; 34(3): 209-215, sept. 2020. ilus, tab
Article in Spanish | LILACS, BINACIS | ID: biblio-1120936

ABSTRACT

La Clasificación de Tumores del Sistema Nervioso Central de la OMS 2016 incorpora biomarcadores moleculares junto a las características histológicas clásicas, en un diagnóstico integrado, con el fin de definir distintas entidades de gliomas con la mayor precisión posible. Los estudios de perfiles moleculares en el genoma han revelado las alteraciones genéticas características y los perfiles epigenéticos asociados con diferentes tipos de gliomas. Estas características moleculares pueden usarse para refinar la clasificación del glioma, mejorar la predicción de los resultados obtenidos con los tratamientos actuales y futuros en los pacientes, y como guía de un tratamiento personalizado. Asimismo, tener una aproximación pronóstica en cada paciente. Este cambio de paradigma ha modificado la forma en que se diagnostica el glioma y sus implicancias en la práctica diaria en la indicación de los diferentes tratamientos al paciente. Aquí, sintéticamente, revisamos y destacamos los biomarcadores moleculares clínicamente relevantes. Intentamos dejar plasmado cómo los avances en la genética molecular de los gliomas pueden promover y allanar el camino hacia la medicina de precisión en neurooncología.


The Classification of Tumors of the Central Nervous System of the WHO 2016 incorporates molecular biomarkers together with the classical histological characteristics, in an integrated diagnosis, in order to define different glioma entities with the highest possible accuracy. Studies of molecular profiles in the genome have revealed characteristic genetic alterations and epigenetic profiles associated with different types of gliomas. These molecular characteristics can be used to refine the classification of gliomas, improve the prediction of the results obtained with current and future treatments in patients and as a guide for a personalized treatment. Also, have a prognostic approach in each patient. This paradigm shift has modified the way glioma is diagnosed and its implications in daily practice in the indication of different treatments to the patient. Here, synthetically, we review and highlight clinically relevant molecular biomarkers. We try to capture how advances in the molecular genetics of gliomas can promote and pave the way to precision medicine in neuro-oncology.


Subject(s)
Humans , Glioma , Biomarkers , Central Nervous System , Molecular Biology , Neoplasms
17.
Rev. bras. oftalmol ; 79(4): 276-277, July-Aug. 2020. graf
Article in English | LILACS | ID: biblio-1137971

ABSTRACT

Abstract Cerebellar astrocytoma (low-grade glioma) is the most frequent tumor of the Central Nervous System in pediatric age, corresponding to 10-20% of brain tumors, having its maximum incidence at 5 years. Brain tumors are the second cause of death at this age, behind leukemias. Its most frequent clinic is headache with vomiting which can worsen in the morning and awaken the patient at night. The most frequent ophthalmological clinic is papilledema and involvement of the cranial nerve VI. In our case we present an atypical presentation (cranial IV), in which a quick derivation favored a better prognosis.


Resumo O astrocitoma cerebelar (glioma de baixo grau) é o tumor mais frequente do Sistema Nervoso Central em idade pediátrica, correspondendo a 10-20% dos tumores cerebrais, tendo sua incidência máxima em 5 anos. Os tumores cerebrais são a segunda causa de morte nesta idade, atrás das leucemias. Sua clínica mais frequente é a cefaleia com vômitos que podem piorar pela manhã e despertar o paciente à noite. A clínica oftalmológica mais frequente é o papiledema e o envolvimento do nervo craniano VI. Em nosso caso apresentamos uma apresentação atípica (IV craniana), em que uma derivação rápida favoreceu um melhor prognóstico.


Subject(s)
Humans , Child, Preschool , Astrocytoma/diagnostic imaging , Brain Neoplasms/diagnostic imaging , Papilledema/physiopathology , Glioma/diagnostic imaging , Headache/physiopathology , Tomography, X-Ray Computed/methods
18.
Arq. neuropsiquiatr ; 78(1): 34-38, Jan. 2020. graf
Article in English | LILACS | ID: biblio-1088980

ABSTRACT

Abstract Brain tumors are one of the most common causes of cancer-related deaths around the world. Angiogenesis is critical in high-grade malignant gliomas, such as glioblastoma multiforme. Objective: The aim of this study is to comparatively analyze the angiogenesis-related genes, namely VEGFA, VEGFB, KDR, CXCL8, CXCR1 and CXCR2 in LGG vs. GBM to identify molecular distinctions using datasets available on The Cancer Genome Atlas (TCGA). Methods: DNA sequencing and mRNA expression data for 514 brain lower grade glioma (LGG) and 592 glioblastoma multiforme (GBM) patients were acquired from The Cancer Genome Atlas (TCGA), and the genetic alterations and expression levels of the selected genes were analyzed. Results: We identified six distinct KDR mutations in the LGG patients and 18 distinct KDR mutations in the GBM patients, including missense and nonsense mutations, frame shift deletion and altered splice region. Furthermore, VEGFA and CXCL8 were significantly overexpressed within GBM patients. Conclusions: VEGFA and CXCL8 are important factors for angiogenesis, which are suggested to have significant roles during tumorigenesis. Our results provide further evidence that VEGFA and CXCL8 could induce angiogenesis and promote LGG to progress into GBM. These findings could be useful in developing novel targeted therapeutics approaches in the future.


Resumo Os tumores cerebrais são uma das causas mais comuns de mortes relacionadas ao câncer em todo o mundo. A angiogênese tem caráter crítico em gliomas malignos de alto grau, como o glioblastoma multiforme. Objetivo: O objetivo deste estudo foi analisar comparativamente os genes relacionados à angiogênese, VEGFA, VEGFB, KDR, CXCL8, CXCR1 e CXCR2 em GBG vs. GBM para identificar distinções moleculares usando conjuntos de dados disponíveis no The Cancer Genome Atlas (TCGA). Métodos: Os dados de sequenciamento de DNA e expressão de mRNA para 514 pacientes com glioma cerebral de baixo grau (GBG) e 592 pacientes com glioblastoma multiforme (GBM) foram adquiridos do TCGA e as alterações genéticas e os níveis de expressão dos genes selecionados foram analisados. Resultados: Identificamos seis mutações KDR distintas nos pacientes GBG e 18 mutações KDR distintas nos pacientes GBM, incluindo mutações missense e nonsense, exclusão de mudança de quadro e região de emenda alterada. Além disso, VEGFA e CXCL8 foram significativamente super-expressos nos pacientes com GBM. Conclusões: VEGFA e CXCL8 são fatores importantes para a angiogênese, os quais parecem ter um papel significativo durante a tumorigênese. Nossos resultados fornecem evidências adicionais de que o VEGFA e o CXCL8 podem induzir a angiogênese e promover o GBG a progredir no GBM. Esses achados podem ser úteis no desenvolvimento de novas abordagens terapêuticas direcionadas no futuro.


Subject(s)
Humans , Brain Neoplasms/genetics , Glioblastoma/genetics , Carcinogenesis/genetics , Glioma/genetics , Neovascularization, Pathologic/genetics , Reference Values , Gene Expression , Interleukin-8/analysis , Point Mutation/genetics , Glioblastoma/pathology , Receptors, Interleukin-8A/analysis , Receptors, Interleukin-8B/analysis , Vascular Endothelial Growth Factor Receptor-2/analysis , Vascular Endothelial Growth Factor A/analysis , Vascular Endothelial Growth Factor B/analysis , Glioma/pathology
19.
Rev. méd. Panamá ; 40(1): 14-20, ene.2020. ilus, tab
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1099573

ABSTRACT

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/physiopathology
20.
Acta Physiologica Sinica ; (6): 235-242, 2020.
Article in Chinese | WPRIM | ID: wpr-827064

ABSTRACT

Gliomas are malignant tumors with strong invasiveness. The current treatment strategy is surgical treatment assisted by a variety of radiotherapies, chemotherapies and immunotherapies. However, the curative efficacy is limited. Adrenergic receptor (AR) is an important stress hormone receptor, which is highly involved in the regulation of the tumorigenesis and progression of various tumors by activating different downstream signal transduction pathways. Recent studies have shown that AR is dysregulated in glioma cells and tissues, and plays an important role in a series of biological behaviors such as tumorigenesis, invasion and metastasis of glioma. This article reviews the research progress of AR in the field of glioma in recent years, which provides a theoretical basis for the prevention and treatment of glioma targeting the AR.


Subject(s)
Brain Neoplasms , Pathology , Carcinogenesis , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Glioma , Pathology , Humans , Neoplasm Invasiveness , Neoplasm Metastasis , Receptors, Adrenergic , Physiology , Signal Transduction
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