Epidemiological Profile of 96 Intracranial Tumors Treated in a Single Reference Center

Objectives The present study aims to categorize the prevalence of intracranial tumors surgically treated at the neurosurgery service of Hospital Universitário Evangélico Mackenzie (HUEM) between 2016 and 2018. Material and Methods This survey included patients surgically treated due to primary or metastatic intracranial neoplasia between 2016 and 2018 at a referral center in the city of Curitiba. These patients were analyzed for epidemiological, histopathological, and topographic data, and they underwent an assessment of the outcome at the time of hospital discharge. Results Atotal of 96patientsmet the inclusion criteria. Themost prevalent tumorwas the glioma, with 39.6% of the sample, with glioblastoma being themost prevalent histological type. Brainmetastases andmeningiomas represented, respectively, 21.9%and 18.8%of the total. There was a predominance of supratentorial and intra-axial tumors in our sample. Conclusion Glioma was the most commonly found tumor, directly associated with high morbidity and mortality. The development of new and more effective drugs with action directed at themolecular level of intracranial tumorsmay be the path to a longer survival and improvement in the quality of life of these patients.

Expression of Glutathione Peroxidases and Its Effect on Clinical Prognosis in Glioma Patients / 中国医学科学院学报

Objective To investigate the relationship between the expression of glutathione peroxidase(GPX)genes and the clinical prognosis in glioma patients,and to construct and evaluate the model for predicting the prognosis of glioma. Methods The clinical information and GPX expression of 663 patients,including 153 patients of glioblastoma(GBM)and 510 patients of low-grade glioma(LGG),were obtained from The Cancer Genome Atlas(TCGA)database.The relationship between GPX expression and patient survival was analyzed.The key GPX affecting the prognosis of glioma was screened out by single- and multi-factor Cox's proportional-hazards regression models and validated by least absolute shrinkage and selection operator(Lasso)regression.Finally,we constructed the model for predicting the prognosis of glioma with the screening results and then used concordance index and calibration curve respectively to evaluate the discrimination and calibration of model. Results Compared with those in the control group,the expression levels of GPX1,GPX3,GPX4,GPX7,and GPX8 were up-regulated in glioma patients(all P<0.001).Moreover,the expression levels of other GPX except GPX3 were higher in GBM patients than in LGG patients(all P<0.001).The Kaplan-Meier curves showed that the progression-free survival of GBM with high expression of GPX1(P=0.013)and GPX4(P=0.040),as well as the overall survival,disease-specific survival,and progression-free survival of LGG with high expression of GPX1,GPX7,and GPX8,was shortened(all P<0.001).GPX7 and GPX8 were screened out as the key factors affecting the prognosis of LGG.The results were further used to construct a nomogram model,which suggested GPX7 was the most important variable.The concordance index of the model was 0.843(95%CI=0.809-0.853),and the calibration curve showed that the predicted and actual results had good consistency. Conclusion GPX7 is an independent risk factor affecting the prognosis of LGG,and the nomogram model constructed with it can be used to predict the survival rate of LGG.

Inhibition of Ciliogenesis Enhances the Cellular Sensitivity to Temozolomide and Ionizing Radiation in Human Glioblastoma Cells / 生物医学与环境科学（英文）

Objective@#To investigate the function of primary cilia in regulating the cellular response to temozolomide (TMZ) and ionizing radiation (IR) in glioblastoma (GBM).@*Methods@#GBM cells were treated with TMZ or X-ray/carbon ion. The primary cilia were examined by immunostaining with Arl13b and γ-tubulin, and the cellular resistance ability was measured by cell viability assay or survival fraction assay. Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride, the autophagy was measured by acridine orange staining assay. The DNA damage repair ability was estimated by the kinetic curve of γH2AX foci, and the DNA-dependent protein kinase (DNA-PK) activation was detected by immunostaining assay.@*Results@#Primary cilia were frequently preserved in GBM, and the induction of ciliogenesis decreased cell proliferation. TMZ and IR promoted ciliogenesis in dose- and time-dependent manners, and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR. The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair. The interference of ciliogenesis reduced DNA-PK activation, and the knockdown of DNA-PK led to cilium formation and elongation.@*Conclusion@#Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.

Primary Extra-axial Glioblastoma: Case Report and Literature Review

Glioblastoma multiforme (GBM) is the most frequent and most aggressive primary brain tumor in adults,mainly located in the cerebral hemispheres. In the literature, few cases of primary GBM have been reported to have radiographic and intraoperative features of extra-axial lesions, leading to a diagnostic dilemma. Despite the advances in imaging modalities, the diagnosis of GBM can be challenging, and it is mainly based on the histopathologic confirmation of the excised tumor. We describe the case of a 76- year-old previously healthy female patient who presented to our hospital due to speech disturbances and cognitive impairment. The diagnosis of the tumor type on magnetic resonance imaging (MRI) was difficult, as the findings were suggestive of a malignant meningioma due to the heterogeneous enhancement of a dural-based mass with a dural tail sign. Moreover, the intraoperative findings revealed an extra-axial mass attached to the dura. A histological examination confirmed the diagnosis of glioblastoma with arachnoid infiltration. The patient underwent adjuvant radiotherapy and concomitant temozolomide treatment, she had clinical improvement postoperatively, and was stable during the six months of follow-up. Glioblastoma should be considered in the differential diagnosis of primary extra-axial mass with atypical and malignant features, especially in elderly patients.

Xantoastrocitoma pleomórfico anaplásico y glioblastoma epitelioide: misma entidad o precursor de enfermedad / Anaplastic pleomorphic xanthoastrocytoma and epithelioid glioblastoma: same entity or precursor of disease / Xantoastrocitoma pleomórfico anaplásico e glioblastoma epitelioide: mesma entidade ou precursor de doença

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.

Anesthetic management in neurological disorders: is combined spinal-epidural a suitable option? Case report / Manejo anestésico en trastornos neurológicos: ¿es la anestesia espinal-epidural una alternativa apropiada? Reporte de caso

Abstract Tuberous sclerosis (TSC) is a rare disease with multi-systemic involvement, predominantly neurological. Little evidence exists about the anesthetic management of patients with this disorder, particularly in pregnant women. This article discusses a case of a patient with TSC admitted to our hospital for the delivery of a twin gestation. Twenty-four hours after surgery, the patient presented left-side facial-brachial hypoesthesia and headache. A brain CT revealed a right frontal cortical bleeding tumor, which was diagnosed as glioblastoma multiforme. The patient was discharged 15 days after admission and a neurosurgical approach was suggested.

Resumen La esclerosis tuberosa es una enfermedad poco frecuente asociada con compromiso multisistémico, principalmente neurológico. Es poca la evidencia sobre el manejo anestésico de los pacientes con este trastorno, en particular las mujeres embarazadas. En este artículo presentamos el caso de una paciente con esclerosis tuberosa ingresada en nuestro hospital para el parto de una gestación gemelar. Veinticuatro horas después de la cirugía, la paciente presentó hipoestesia facial y braquial izquierda y cefalea. La tomografía cerebral mostró un tumor cortical sangrante en el lóbulo frontal derecho, diagnosticado como glioblastoma multiforme. La paciente fue dada de alta 15 días después de su ingreso y, con recomendación de manejo por neurocirugía.

Microsurgical Resection of Glioblastoma in a Patient Infected with Covid-19: A Case Report

The COVID-19 pandemic has affected a large number of patients in all countries, overwhelming healthcare systems worldwide. In this scenario, surgical procedures became restricted, causing unacceptable delays in the treatment of certain pathologies, such as glioblastoma. Regarding this tumor with high morbidity and mortality, early surgical treatment is essential to increase the survival and quality of life of these patients. Association between COVID-19 and neurosurgical procedures is quite scarce in the literature, with a few reported cases. In the present study, we present a rare case of a patient undergoing surgical resection of glioblastoma with COVID-19.

Approaching glioblastoma during COVID-19 pandemic: current recommendations and considerations in Brazil / Abordando glioblastomas durante a pandemia pelo COVID-19: recomendações atuais e considerações no Brasil

ABSTRACT Background: Cancer patients in general and glioblastoma patients, in particular, have an increased risk of developing complications from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and reaching a balance between the risk of exposure to infection and the clinical benefit of their treatment is ideal. The aggressive behavior of this group of tumors justifies the need for a multidisciplinary team to assist in clinical decisions during the current pandemic. Brazil is now ranked #2 in the number of cases and deaths from COVID-19 pandemic, and existing disparities in the treatment of neuro-oncology patients in Brazil will challenge the clinical and surgical decisions of this population, possibly affecting global survival. Objective: To search the literature about the management of glioblastomas during COVID-19 pandemic to guide surgical and clinical decisions in this population of patients in Brazil. Methods: We performed a systematic search on the PubMed electronic database targeting consensus statements concerning glioblastoma approaches during COVID-19 pandemic up to July 18, 2020. Results: When approaching glioblastoma during the COVID-19 pandemic, important parameters that help in the decision-making process are age, performance status, tumor molecular profile, and patient consent. Younger patients should follow the standard protocol after maximal safe resection, mainly those with MGMT methylated tumors. Aged and underperforming patients should be carefully evaluated, and probably a monotherapy scheme is to be considered. Centers are advised to engage in telemedicine and to elaborate means to reduce local infection. Conclusion: Approaching glioblastoma during the COVID-19 pandemic will be challenging worldwide, but particularly in Brazil, where a significant inequality of healthcare exists.

RESUMO Introdução: Pacientes com câncer, em geral, e particularmente pacientes com glioblastoma estão sob elevado risco de desenvolver síndrome respiratória aguda grave devido à infecção pelo SARS-CoV-2, e alcançar um equilíbrio entre risco de exposição à infecção e benefício clínico do tratamento seria o ideal. O comportamento agressivo desse grupo de tumores justifica a necessidade de equipe multidisciplinar para auxiliar nas decisões clínicas durante a pandemia vigente. O Brasil ocupa hoje o segundo lugar em número de casos e óbitos pela COVID-19, e as atuais disparidades no tratamento de pacientes neuro-oncológicos desafiarão as decisões clínicas e cirúrgicas dessa população, possivelmente afetando a sobrevida global. Objetivo: Guiar decisões clínicas e cirúrgicas relacionadas ao manejo de glioblastoma durante a pandemia pelo COVID-19 no Brasil por meio de pesquisa em literatura. Métodos: Busca sistemática no banco de dados eletrônico da PubMed por estudos ou consensos quanto à abordagem de glioblastoma durante a pandemia por COVID-19 até 18/07/2020. Resultado: Ao abordar o glioblastoma durante a pandemia pela COVID-19, parâmetros importantes que auxiliam no processo de tomada de decisão são idade, desempenho, perfil molecular tumoral e consentimento do paciente. Pacientes jovens devem seguir protocolo padrão após máxima ressecção cirúrgica, principalmente aqueles com metilação do promotor MGMT. Idosos e pacientes debilitados devem ser cuidadosamente avaliados, e monoterapia deve ser provavelmente considerada. Centros de saúde são orientados a utilizar-se da telemedicina e de meios para reduzir infecção local. Conclusão: A abordagem do glioblastoma durante a pandemia por COVID-19 será mundialmente desafiadora, mas particularmente no Brasil, onde ainda existe significativa inequidade no cuidado com a saúde.

Nuclear Dbf2-related Kinase 1 functions as tumor suppressor in glioblastoma by phosphorylation of Yes-associated protein / 中华医学杂志(英文版)

BACKGROUND@#The Nuclear Dbf2-related (NDR1) kinase is a member of the NDR/LATS family, which was a supplementary of Hippo pathway. However, whether NDR1 could inhibit glioblastoma (GBM) growth by phosphorylating Yes-associated protein (YAP) remains unknown. Meanwhile, the role of NDR1 in GBM was not clear. This study aimed to investigate the role of NDR1-YAP pathway in GBM.@*METHODS@#Bioinformation analysis and immunohistochemistry (IHC) were performed to identify the expression of NDR1 in GBM. The effect of NDR1 on cell proliferation and cell cycle was analyzed utilizing CCK-8, clone formation, immunofluorescence and flow cytometry, respectively. In addition, the xenograft tumor model was established as well. Protein interaction was examined by Co-immunoprecipitation and immunofluorescence to observe co-localization.@*RESULTS@#Bioinformation analysis and IHC of our patients' tumor tissues showed that expression of NDR1 in tumor tissue was relatively lower than that in normal tissues and was positively related to a lower survival rate. NDR1 could markedly reduce the proliferation and colony formation of U87 and U251. Furthermore, the results of flow cytometry showed that NDR1 led to cell cycle arrest at the G1 phase. Tumor growth was also inhibited in xenograft nude mouse models in NDR1-overexpression group. Western blotting and immunofluorescence showed that NDR1 could integrate with and phosphorylate YAP at S127 site. Meanwhile, NDR1 could mediate apoptosis process.@*CONCLUSION@#In summary, our findings point out that NDR1 functions as a tumor suppressor in GBM. NDR1 is identified as a novel regulator of YAP, which gives us an in-depth comprehension of the Hippo signaling pathway.

Overexpression of lncRNA MEG3 inhibits proliferation and invasion of glioblastoma U251 cells / 南方医科大学学报

OBJECTIVE@#To investigate the effects of overexpression of long noncoding RNA (lncRNA) MEG3 on the proliferation and invasion of glioblastoma U251 cells by suppressing the expression of hypoxia inducible factor 1@*METHODS@#The expression of lncRNA MEG3 and HIF1@*RESULTS@#The expression of MEG3 was significantly lower and HIF1@*CONCLUSIONS@#MEG3 overexpression inhibits the proliferation and invasion of U251 cells through suppressing the expression of HIF1

Intratumor heterogeneity, microenvironment, and mechanisms of drug resistance in glioma recurrence and evolution / 医学前沿

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.

Effects of tetrandrine on proliferation, migration, and invasion of glioblastoma cells / 中国中药杂志

Glioblastoma is the most common intracranial primary malignant tumor, which leads to the poor quality of life of patients and has a high recurrence rate. Chemotherapy is a vital part in the treatment of this disease. Tetrandrine(Tet) is an active ingredient extracted from the root of the Chinese medicinal plant Stephania tetrandra, which has been proved with a wide range of pharmacological effects including anti-tumor. However, there are few studies regarding the effect of Tet on glioma. In this study, MTT and BrdU assays were employed to detect the effect of Tet on the proliferation of LN229 glioblastoma cells; flow cytometry was used to analyze the cycle distribution and apoptosis; plate cloning assay and soft agar colony formation assay were performed to study the colony formation ability of LN229 cells exposed to Tet; scratch assay and Transwell assay were conducted to detect the ability of migration and invasion; Western blot was adopted to the exploration of the molecular mechanism. The MTT and BrdU assays showed that Tet inhibited the proliferation of LN229 cells in a time-and dose-dependent manner. The plate cloning assay and soft agar colony formation assay showed that Tet weakened the colony formation of LN229 cells in vitro; cytometry assay showed that Tet blocked cells in the G_1 phase and promoted cell apoptosis; scratch and Transwell assays proved that Tet inhibited the migration and invasion of LN229 cells; Western blot results showed that Tet down-regulated the expression levels of CDK2, CDK6, cyclin D1, cyclin E1, snail, slug, vimentin, and N-cadherin, while up-regulated the level of E-cadherin. The results indicate that Tet has a certain inhibitory effect on the proliferation, migration, and invasion of LN229 glioblastoma cells, and such effect may be related to the participation of Tet in the regulation of c-Myc/p27 axis and snail signaling pathway.

Genomic and transcriptomic characterization of the human glioblastoma cell line AHOL1

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.

Perfil Anatomopatológico e Imuno-histoquímico de Gliomas de Pacientes da Região de Maringá-PR / Anatomopathological and Immunohistochemical Profile of Gliomas of Patients in the Region of Maringá-PR / Perfil Anatomopatológico e Inmunohistoquímico de Gliomas en Pacientes la Región de Maringá-PR

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

Detección de la mutación de la enzima isocitrato deshidrogenasa en gliomas difusos grados II, III y IV / Detection of isocitrate dehydrogenase enzyme mutation in grades II, III and IV diffuse gliomas

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

The protective role of selenium against dental amalgam-induced intracellular oxidative toxicity through the TRPV1 channel in DBTRG glioblastoma cells

Abstract Objective The exposure to mercury (Hg) from dental amalgams is a suspected causative factor in neurological diseases. This study investigated the toxic effects of two different amalgam compositions related to Hg and the protective effects of selenium against the toxic effects of Hg through the TRPV1 channel in the human DBTRG glioblastoma cell line. Methodology Six groups of the cells were organized. Analyses of cell viability, apoptosis, caspase 3 and caspase 9 activities, mitochondrial membrane depolarization, reactive oxygen species (ROS) production, and Western Blotting for protein expression levels were performed. Results Cell viability values were lower in amalgam with high copper (HCu) and low copper (LCu) groups independently of time but were increased by selenium and capsazepine (p<0.001 and p<0.05). Conversely, apoptosis rates, caspase 3 and caspase 9 expression, ROS formation, mitochondrial membrane depolarization, and protein expression levels were higher in the HCu and LCu groups but were decreased by selenium (p<0.001 and p<0.05). Conclusions Selenium combined with an amalgam of either HCu or LCu decreases the toxic effects created by Hg in human DBTRG glioblastoma cells.

Glioblastoma de células gigantes: informe de un caso / Giant cell glioblastoma: case report

Antecedentes: El Glioblastoma (GB) o astrocitoma grado IV, es un tumor agresivo que se origina de células gliales, con alto grado de malignidad, prevalencia menor al 1% en fosa posterior e incidencia menor al 0.5% de todos los GB. Actualmente se describen alrededor de 75 casos a nivel mundial. Descripción del caso clínico: Femenina, 24 años, referida a emergencia de Neurocirugía del Hospital Escuela Universitario, presentó cefalea holocraneana intensa, vómitos, náuseas, visión borrosa, vértigo y anorexia. Al examen neurológico mostró discreta adiadococinesia derecha y signos de papiledema. La tomografía axial computarizada cerebral evidenció lesión heterogénea en vermis extendido a hemisferio cerebeloso derecho, por lo que se realizó craniectomía suboccipital, abordaje transcerebelar, con citorreducción tumoral, encontrando masa vascularizada con componente quístico. Estudio anatomopatológico evidenció glioblastoma multiforme variante de células gigantes, confirmado con tinción de inmunohistoquímica (PFGA, CD34+ y vimentina). Paciente con buena evolución clínica postquirúrgica, egresada sin déficit neurológico. 16 meses después, presentó síndrome de recidiva tumoral y complicaciones, por lo que se reintervino en 4 ocasiones, posterior a recibir 30 dosis de radioterapia y 12 ciclos de quimioterapia, se reingresó con deterioro neurológico progresivo, signos meníngeos y síndrome de Parinaud, escala de Karnofsky (30 puntos), realizándose derivación ventrículo-peritoneal por compresión del IV ventrículo e hidrocefalia obstructiva secundaria, luego desarrolló neumonía intrahospitalaria, falleciendo a las dos semanas. Conclusiones: Es importante identificar la variante biológica del glioblastoma de forma temprana, para determinar pronóstico y acciones terapéuticas que influirán en la calidad de vida, así como la supervivencia...(AU)

Temozolamide as an adjuvant in glioblastoma. How long? The experience of a cancer center in Colombia / Temozolamide como adyuvancia en glioblastoma. ¿Por cuánto tiempo?. Experiencia en un centro oncológico de Colombia

Abstract Introduction: glioblastoma multiforme is considered to be highly lethal, for which the optimal duration of adjuvant temozolamide chemotherapy has not been determined. Objective: to evaluate survival according to the length of adjuvant chemotherapy based on the standard Stupp platform protocol. Materials and methods: a retrospective cohort analysis of 299 high-grade central nervous system tumors seen at Oncólogos del Occidente, focused solely on glioblastoma multiforme, according to clinical, treatment and outcome variables. Results: one hundred ninety-three patients with glioblastoma; 84 (44%) received standard Stupp platform treatment; mean age 54 years; 55% males; mean tumor size 28,793 mm2; 48% right hemisphere; 21% crossed the midline; 33% had seizures and 42% neurological deficit; 55% Karnofsky less than 70% and 66% RPA IV classification; 77% received radiation with 60.00 Gy or more; 19% had complications; 79% partial resection and 12% total resection; 77% relapsed; at closure, 57% were alive, global survival of 26% and mean of 26 months, with a difference of 31 months for adjuvance of <or> 6 months and 30 months for adjuvance of <or> 12 months, without reaching a median in the 18 and 24 month groups, all of them favoring the group with the longest time. Conclusion: a clear increase in survival is shown with adjuvant temozolamide for periods longer than six months, as well as a tendency towards better results with increased duration of adjuvance.

Resumen Introducción: el glioblastoma multiforme se considera altamente letal, donde la duración óptima de quimioterapia adyuvante con base en temozolamide no ha sido definida. Objetivo: evaluar la sobrevida según la duración de quimioterapia adyuvante basada en el esquema estándar de plataforma Stupp. Material y métodos: análisis de cohorte retrospectiva de 299 tumores del sistema nervioso central de alto grado, valorados en Oncólogos del Occidente enfocado sólo a glioblastoma multiforme según variables clínicas, terapéuticas y de resultados. Resultados: ciento noventa y tres pacientes con glioblastoma, 84 (44%) recibieron manejo estándar tipo plataforma Stupp; edad media 54 años; hombres 55%; tamaño tumoral medio 28.79 mm2; hemisferio derecho 48%; 21% cruzaban línea media; 33% presentaron convulsiones y 42% déficit neurológico; 55% Karnofsky menor a 70% y 66% clasificación RPA IV; 77% recibieron radioterapia con 60.00 Gys o mayor; 19% presentaron complicaciones; resección parcial 79% y 12% total; 77% recayeron; al cierre 57% se encontraban vivos, sobrevida global de 26% y media de 26 meses con diferencia de 31 meses para adyuvancia en <o> a 6 meses y 30 meses en adyuvancia <o> a 12 meses sin alcanzar mediana en los grupos <o> de 18 y 24 meses favoreciendo en todos al grupo de mayor tiempo. Conclusión: se demuestra aumento claro en la sobrevida con el empleo de temozolamide adyuvante por periodos mayores a seis meses y una tendencia a mejores resultados mientras mayor sea el tiempo de adyuvancia.