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Rev. colomb. anestesiol ; 49(3): e600, July-Sept. 2021. tab, graf
Article in English | LILACS, COLNAL | ID: biblio-1280183


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.

Humans , Female , Pregnancy , Cesarean Section , Glioblastoma , Headache , Anesthesia, Epidural , Anesthetics , Neurosurgery , Tuberous Sclerosis , Brain , Rare Diseases , Parturition , Hemorrhage , Hospitals , Hypesthesia , Neoplasms , Nervous System Diseases
Article in Chinese | WPRIM | ID: wpr-880841


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

Apoptosis , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Glioblastoma/genetics , Humans , MicroRNAs , RNA, Long Noncoding/genetics
J. appl. oral sci ; 29: e20200414, 2021. tab, graf
Article in English | LILACS | ID: biblio-1154614


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.

Humans , Selenium/pharmacology , Glioblastoma , Cell Survival , Oxidative Stress , Dental Amalgam , TRPV Cation Channels
Rev. méd. hondur ; 89(1, supl): 18-22, 2021. ilus
Article in Spanish | LILACS | ID: biblio-1247576


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)

Humans , Female , Adult , Brain Neoplasms/complications , Glioblastoma/diagnosis , Cerebellar Ataxia , Glial Fibrillary Acidic Protein
Braz. j. med. biol. res ; 54(3): e9571, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153526


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.

Humans , Glioblastoma/genetics , Gene Expression Regulation, Neoplastic , Minor Histocompatibility Antigens , Genome , Genomics , Cell Line, Tumor , Histone Demethylases , Transcriptome
Acta méd. colomb ; 45(4): 9-19, Oct.-Dec. 2020. tab, graf
Article in English | LILACS, COLNAL | ID: biblio-1278136


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.

Humans , Male , Middle Aged , Central Nervous System Neoplasms , Glioblastoma , Central Nervous System , Chemotherapy, Adjuvant , Survivorship , Neoplasms
Rev. Assoc. Med. Bras. (1992) ; 66(6): 794-799, June 2020. graf
Article in English | LILACS, SES-SP | ID: biblio-1136287


SUMMARY OBJECTIVES HOXB2 is a new prognostic indicator for lung cancer. But it is unclear whether HOXB2 holds an effect in glioblastoma (GBM) progression. The purpose of this article was to probe the influences of HOXB2 on GBM pathogenesis. METHODS HOXB2 expression level and prognostic power in GBM patients were analyzed. Then the mRNA and protein expression levels of HOXB2 in GBM cell lines were tested by qRT-PCR and western blotting. Cell proliferation, invasion, and migration were determined by CCK8 and transwell assay, severally. The protein levels of PI3K/AKT-pathway associated proteins were analyzed by western blotting. RESULTS The results indicated that HOXB2 was distinctly overexpressed in GBM patients and high expression of HOXB2 was related to a poor prognosis. Moreover, the expression of HOXB2 was higher in all GBM cell lines U251, U-87MG, GOS-3 than that in HEB cells (normal control). Meanwhile, decreased expression of p-PI3K and p-AKT were identified after HOXB2 knockdown. CONCLUSIONS These data demonstrated that HOXB2 had a vital role in GBM progression and could serve as a promising target for GBM treatment.

RESUMO OBJETIVOS A HOXB2 é um novo indicador prognóstico para o câncer de pulmão. Mas não está claro se a HOXB2 tem algum efeito na progressão do glioblastoma (GBM). O objetivo deste artigo foi sondar as influências da HOXB2 na patogênese do GBM. MÉTODOS Foram analisados o nível de expressão e o poder prognóstico da HOXB2 em pacientes com GBM. Em seguida, os níveis de expressão proteica e mRNA da HOXB2 em linhagens de células de GBM foram testados por qRT-PCR e western blotting. A proliferação, a invasão e migração celular foram determinadas por CCK8 e ensaios transwell, várias vezes. Os níveis proteicos das proteínas associadas à via PI3K/AKT foram analisados pelo método western blotting. RESULTADOS Os resultados indicaram que havia uma clara superrexpressão da HOXB2 em pacientes com GBM e que a alta expressão da HOXB2 estava relacionada a um prognóstico negativo. Além disso, a expressão da HOXB2 foi mais elevada em todas as linhagens de células do GBM U251, U-87MG, GOS-3 do que nas células HEB (controle normal). Entretanto, a diminuição da expressão de P-PI3K e p-AKT foi identificada após a redução da expressão da HOXB2. CONCLUSÕES Esses dados demonstram que a HOXB2 desempenha um papel vital na progressão do GBM, podendo ser um alvo promissor para o tratamento do GBM.

Humans , Brain Neoplasms/diagnosis , Genes, Homeobox/physiology , Glioblastoma/diagnosis , Prognosis , Biomarkers , Gene Expression Regulation, Neoplastic , Phosphatidylinositol 3-Kinases , Cell Line, Tumor , Cell Proliferation
Rev. méd. Panamá ; 40(1): 14-20, ene.2020. ilus, tab
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1099573


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

Humans , Male , Female , Middle Aged , Astrocytes/pathology , Glioma/epidemiology , Oligodendroglioma/epidemiology , Magnetic Resonance Imaging/methods , Glioblastoma/physiopathology
Arq. neuropsiquiatr ; 78(1): 34-38, Jan. 2020. graf
Article in English | LILACS | ID: biblio-1088980


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.

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
Rev Assoc Med Bras (1992) ; 66(4): 445-451, 2020. graf
Article in English | LILACS, SES-SP | ID: biblio-1136233


SUMMARY OBJECTIVE Glioblastoma (GBM) is a common type of cancer with high mortality. Epithelial to mesenchymal transition (EMT) plays a vital role in the development of glioblastoma. The aim of this study is to evaluate the role of miR-125a-5p in glioblastoma and in the tumorigenesis of chemotherapeutic drug-resistant cancer stem-like cells in brain glioma. METHODS The role of miR-125a-5p in the regulation of CSCs, EMT, migration, and invasion in glioblastoma was measured in this study. RESULTS We showed the roles of miR-125a-5p in the regulation of CSCs, EMT, migration, and invasion in glioblastoma. miR-125a-5p can inhibit the CSCs phenotype and EMT in glioblastoma cells. In addition, its over-expression can significantly regulate CSCs-associated genes and EMT-associated gene expression in glioblastoma cells. CONCLUSIONS We concluded that miR-125a-5p is one of the key microRNAs regulating CSCs and EMT programs in glioblastoma. The results suggested that miR-125a-5p might be a novel therapy target for glioblastoma.

RESUMO OBJETIVO O glioblastoma (GBM) é um câncer comum e de alta mortalidade. A transição epitélio-mesênquima (EMT) desempenha um papel vital no desenvolvimento do glioblastoma. O objetivo deste estudo é avaliar o papel do miR-125a-5p no glioblastoma e a tumorigênese de células-troco cancerígenas resistentes a medicamentos quimioterápicos em gliomas cerebrais. METODOLOGIA Os papéis do miR-125a-5p na regulação de células-tronco cancerígenas, EMT, migração e invasão do glioblastoma foram medidos neste estudo. RESULTADOS Mostramos a função do miR-125a-5p na regulação das células-tronco cancerígenas, EMT, migração e invasão do glioblastoma. O miR-125a-5p pode inibir o fenótipo e a EMT de células-tronco cancerígenas em células de glioblastoma. Além disso, a sua superexpressão pode regular de forma significante genes associados às células-tronco cancerígenas e a expressão de genes associados à EMT em células de glioblastoma. CONCLUSÕES Concluímos que o miR-125a-5p é um dos principais microRNAs na regulação de células-tronco cancerígenas e programas de EMT em glioblastomas, e os resultados sugerem que o miR-125a-5p pode ser um novo alvo terapêutico em casos de glioblastoma.

Humans , Glioblastoma , MicroRNAs , Phenotype , Neoplastic Stem Cells , Gene Expression Regulation, Neoplastic , Cell Movement , Cell Line, Tumor , Cell Proliferation , Epithelial-Mesenchymal Transition
Clinics ; 75: e1553, 2020. tab, graf
Article in English | LILACS | ID: biblio-1133414


OBJECTIVES: To assess the patterns of failure and prognostic factors in Brazilian patients with glioblastoma multiforme (GBM) treated with radiotherapy (RT) and concurrent and adjuvant temozolomide (TMZ). METHODS: Patients with diagnosed GBM post-resection received postoperative RT. TMZ was administered concurrently at 75 mg/m2/day for 28 consecutive days and adjuvant therapy at 150-200 mg/m2/day for 5 days every 28 days. Radiographic failure was defined as any new T1-enhancing lesion or biopsy-confirmed progressive enhancement inside of the radiation field. When possible, patients with recurrence were salvaged with metronomic TMZ, either in combination with a local treatment or alone (surgery or re-irradiation). Several prognostic factors were evaluated for overall survival (OS). Univariate and multivariate analyses were performed to identify significant factors. A p-value <0.05 was considered significant. RESULTS: This study included 50 patients. The median follow-up time was 21 months. The median RT dose was 60 Gy and all patients received concomitant TMZ. During follow-up, 41 (83.6%) failures were observed, including 34 (83%) in-field, 4 (9.7%) marginal, and 3 (7.3%) distant failures. Metronomic TMZ was used as salvage treatment in 22 (44%) cases and in combination with local treatment in 12 (24%) cases. The median OS and progression-free survival times for the entire cohort were 17 and 9 months, respectively. In univariate analysis, the following factors were significant for better OS: maximal surgical resection (p=0.03), Karnofsky Performance Score (KPS)>70 at diagnosis (p=0.01), metronomic TMZ treatment (p=0.038), recursive partitioning analysis class III (p=0.03), and time to failure >9 months (p=0.0001). In multivariate analysis, the following factors remained significant for better OS: metronomic TMZ (p=0.01) and time to failure >9 months (p=0.0001). CONCLUSION: The median OS of Brazilian patients with GBM treated with RT and TMZ was satisfactory. Although TMZ therapy has become the standard of care for patients with newly diagnosed GBM, the recurrence rate is extremely high. Metronomic TMZ as salvage treatment improved survival in these patients.

Humans , Male , Female , Brain Neoplasms/therapy , Glioblastoma/therapy , Antineoplastic Agents, Alkylating/therapeutic use , Chemoradiotherapy/methods , Temozolomide/therapeutic use , Neoplasm Recurrence, Local/epidemiology , Survival , Brain Neoplasms/pathology , Brazil/epidemiology , Retrospective Studies , Treatment Outcome , Chemotherapy, Adjuvant , Glioblastoma/mortality , Glioblastoma/pathology
Einstein (Säo Paulo) ; 18: eAO4954, 2020. graf
Article in English | LILACS | ID: biblio-1056032


ABSTRACT Objective: To evaluate the magnetic hyperthermia therapy in glioblastoma tumor-on-a-Chip model using a microfluidics device. Methods: The magnetic nanoparticles coated with aminosilane were used for the therapy of magnetic hyperthermia, being evaluated the specific absorption rate of the magnetic nanoparticles at 300 Gauss and 305kHz. A preculture of C6 cells was performed before the 3D cells culture on the chip. The process of magnetic hyperthermia on the Chip was performed after administration of 20μL of magnetic nanoparticles (10mgFe/mL) using the parameters that generated the specific absorption rate value. The efficacy of magnetic hyperthermia therapy was evaluated by using the cell viability test through the following fluorescence staining: calcein acetoxymethyl ester (492/513nm), for live cells, and ethidium homodimer-1 (526/619nm) for dead cells dyes. Results: Magnetic nanoparticles when submitted to the alternating magnetic field (300 Gauss and 305kHz) produced a mean value of the specific absorption rate of 115.4±6.0W/g. The 3D culture of C6 cells evaluated by light field microscopy imaging showed the proliferation and morphology of the cells prior to the application of magnetic hyperthermia therapy. Fluorescence images showed decreased viability of cultured cells in organ-on-a-Chip by 20% and 100% after 10 and 30 minutes of the magnetic hyperthermia therapy application respectively. Conclusion: The study showed that the therapeutic process of magnetic hyperthermia in the glioblastoma on-a-chip model was effective to produce the total cell lise after 30 minutes of therapy.

RESUMO Objetivo: Avaliar a terapia de magneto-hipertermia em modelo de tumor de glioblastoma on-a-Chip. Métodos: As nanopartículas magnéticas recobertas com aminosilana foram utilizadas para a terapia da magneto-hipertermia, sendo avaliada a taxa de absorção específica das nanopartículas magnéticas em 300 Gauss e 305kHz. Uma pré-cultura de células C6 foi realizada e, seguidamente, foi feito o cultivo das células 3D no chip. O processo de magneto-hipertermia no chip foi realizado após administração de 20μL de nanopartículas magnéticas (10mgFe/mL), utilizando os parâmetros que geraram o valor da taxa de absorção específica. A eficácia da terapia de magneto-hipertermia foi avaliada pela viabilidade celular por meio dos corantes fluorescentes acetoximetiléster de calceína (492/513nm), para células vivas, e etídio homodímero-1 (526/619nm), para células mortas. Resultados: As nanopartículas magnéticas, quando submetidas ao campo magnético alternado (300 Gauss e 305kHz), produziram um valor médio da taxa de absorção específica de 115,4±6,0W/g. A cultura 3D das células C6 avaliada por imagem de microscopia de campo claro mostrou a proliferação e a morfologia das células antes da aplicação da terapia de magneto-hipertermia. As imagens de fluorescência mostraram diminuição da viabilidade das células cultivadas no organ-on-a-Chip em 20% e 100% após 10 e 30 minutos, respectivamente, da aplicação da terapia de magneto-hipertermia. Conclusão: O processo terapêutico da magneto-hipertermia no modelo de tumor glioblastoma on-a-chip foi eficaz para produzir lise total das células após 30 minutos de terapia.

Animals , Rats , Glioblastoma/therapy , Cell Culture Techniques/methods , Lab-On-A-Chip Devices , Magnetite Nanoparticles/therapeutic use , Hyperthermia, Induced/methods , Temperature , Time Factors , Cell Survival , Reproducibility of Results , Treatment Outcome , Cell Line, Tumor , Magnetic Fields , Fluorescence
Chinese Medical Journal ; (24): 2437-2443, 2020.
Article in English | WPRIM | ID: wpr-877835


BACKGROUND@#Epithelial to mesenchymal transition (EMT) is strongly linked with tumor invasion and metastasis, which performs a vital role in carcinogenesis and cancer progression. Emerging evidence suggests that microRNAs (miRNAs) expression are closely associated to EMT by regulating targeted genes. MiR542 has been found to be involved in the EMT program and bound up with various cancers. However, the functions of miR542 and its underlying mechanism in glioblastoma multiforme (GBM) remain largely unknown. In the current study, we investigated the effect of astrocyte elevated gene-1 (AEG-1) on U251 cells aggressiveness, proliferation, apoptosis, and cell cycle.@*METHODS@#The screening of targeted miRNAs was performed, as well as the functional roles and mechanisms of miR542 were explored.@*RESULTS@#MiR542 was selected as the target because of the most significantly differential expression and this high level of expression negatively correlated with cell migration and proliferation, which suggested that miR542 could be a novel tumor suppressor. Moreover, we confirmed that AEG-1 was a direct targeted gene of miR542 by luciferase activity assay, reverse transcription-polymerase chain reaction, and immunoblotting analysis. Furthermore, miR542 suppressed the expression of AEG-1, which upgraded the level of E-cadherin and degraded Vimentin expression contributing to retraining EMT.@*CONCLUSION@#The in vitro findings demonstrated that miR542 inhibited the migration and proliferation of U251 cells and suppressed EMT through targeting AEG-1, indicating that miR542 may be a potential anti-cancer target for GBM.

Astrocytes , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Glioblastoma/genetics , Humans , MicroRNAs/genetics , Neoplasm Invasiveness/genetics
Rev. medica electron ; 41(5): 1230-1241, sept.-oct. 2019. graf
Article in Spanish | LILACS, CUMED | ID: biblio-1094125


RESUMEN A pesar de los avances en radioterapia, quimioterapia y los tratamientos de resección quirúrgica agresiva en el glioblastoma multiforme, el pronóstico sigue siendo sombrío. Con la presente revisión se describen, en un marco actual, las principales alternativas de tratamiento del glioblastoma multiforme. Se revisaron los principales artículos publicados en inglés, en revistas de alto impacto a nivel mundial, acerca de los principales avances en el tratamiento de este tumor. Se abordaron los importantes progresos neuroquirúrgicos en la resección del glioblastoma así como las implicaciones de las células madres tumorales en la génesis y control de la proliferación tumoral y el efecto de la hipoxia sobre la dinámica celular tumoral. Se explican las alteraciones del ADN que ocasionan tumorogénesis y las mutaciones del PTEN en el glioblastoma (AU).

SUMMARY Despite advances in radiotherapy, chemotherapy and aggressive surgical resection treatments in glioblastoma multiforme, the prognosis remains discouraging. With the current review, the main alternatives for the treatment of glioblastoma multiforme are described in a current context. The authors reviewed the main articles published in English, in high impact journals worldwide, on the main advances in the treatment of this tumor. The main neurosurgical advances in the resection of glioblastoma were addressed, as well as the implications of tumor stem cells in the genesis and control of tumor proliferation, as well as the effect of hypoxia on tumor cell dynamics. DNA alterations causing tumor genesis and PTEN mutations in glioblastoma are also explained (AU).

Humans , Glioblastoma/therapy , Glioma/therapy , Glioblastoma/surgery , Neurosurgical Procedures , Glioma/surgery
Int. j. morphol ; 37(3): 800-804, Sept. 2019. graf
Article in Spanish | LILACS | ID: biblio-1012356


El glioblastoma multiforme es el subtipo de gliomas más frecuente en adultos, con una pobre sobrevida promedio posterior al diagnóstico incluso si se aplica el tratamiento óptimo. Se ha estudiado marcadores tumorales de buen pronóstico, siendo controversial la expresión del homólogo de fosfatasa y tensina. Se estudió muestras parafinadas obtenidas de pacientes con glioblastoma multiforme en el Hospital Carlos Van Buren de Valparaíso, Chile, entre 2010 y 2014. Se realizó análisis inmunohistoquímico para expresión de homólogo de fosfatasa y tensina, estudiándose la intensidad y el patrón de expresión en astrocitos y células epiteliales, además de revisión de datos clínicos. Análisis estadístico utilizando SPSS v20. Se estudió la expresión de PTEN en 21 pacientes. Un 52,4 % presentó una baja expresión en núcleos de astrocitos, con un promedio de sobrevida de 14,2 meses comparado con 10,2 meses del grupo con alta expresión (p=0,33). Se encontró una intensa expresión endotelial en tejido tumoral, comparado con tejido cerebral sin tumor. Se encontró una relación entre la expresión nuclear en astrocitos con diferencias en el tiempo de sobrevida, aunque no estadísticamente significativa, requiriéndose nuevos estudios para corroborarlo. La intensa expresión endotelial observada en tejido tumoral debe ser analizada de forma dirigida.

Glioblastoma multiforme is the most frequent glioma subtype in adults, with poor survival rate after diagnosis even applying the optimal treatment. Tumoural markers have been studied looking for good prognosis, being the phosphatase and tensin homologue controversial. Paraffined samples were used from Carlos Van Buren Hospital in Valparaíso, Chile, between 2010 and 2014. An immunohistochemical analysis was performed looking for phosphatase and tensing homologue expression, studying the intensity and expression pattern in astrocytes and epithelial cells, in addition to clinical data. Statistical analysis was performed using SPSS v20. It was studied the phosphatase and tensin homologue expression in 21 patients. In the study, 52,4 % presented low expression in astrocytic glial cell nuclei, with a survival mean of 14.2 months in comparison to 10.2 months in the high expression group (p=0.33). A very intense endothelial expression was found in tumoural tissue, in comparison to the tissue without tumor. A relation between nuclear expression in astrocytes and survival rate was found, although no statistically significant. The intense endothelial expression seen in tumoural tissue must be studied directly.

Humans , Male , Female , Adult , Middle Aged , Aged , Young Adult , Brain Neoplasms/metabolism , Glioblastoma/metabolism , Immunohistochemistry , Survival Analysis , Astrocytes/metabolism , Retrospective Studies , PTEN Phosphohydrolase/metabolism
Rev. Assoc. Med. Bras. (1992) ; 65(3): 424-433, Mar. 2019. tab, graf
Article in English | LILACS | ID: biblio-1003031


SUMMARY OBJECTIVE: Extracranial metastases of glioblastoma multiforme (GBM) are rare due to the short survival experienced by the patients. Therefore, the natural history of GBM metastases remains elusive. The identification of clinical factors promoting GBM metastases may help elucidate the mechanisms of tumor cell invasion in the brain. The aims of this study were to perform a meta-analysis evaluating the survival, characteristics, prognostic factors, and predictors of treatment outcome in patients with metastatic GBM and describe a case of metastatic extracranial GBM. METHODS: We report the case of a patient diagnosed with GBM metastatic to the lungs and the results of a meta-analysis of 114 other cases of metastatic GBM identified through a MEDLINE and BIREME search. RESULTS: The mean age of the patients was 38.2±16.1 years and 70.4% were male. The time elapsed between the identification of the metastasis and death was significantly increased in patients undergoing surgery (p=0.019), whereas the time from the diagnosis of the primary tumor to death was significantly increased in patients receiving radiation therapy (p=0.050). The time elapsed from metastasis to death and diagnosis to death was significantly longer in patients receiving chemotherapy (p<0.001 and p=0.027, respectively). The liver was the metastatic site associated with the shortest time elapsed from diagnosis to death (p=0.024). CONCLUSIONS: In GBM, surgical resection is important in reducing the risk of metastasis, and chemotherapy and radiation therapy help to prolong survival in metastatic GBM. Metastases to the liver are associated with shorter survival compared with metastases to other sites.

RESUMO OBJETIVO: Metástases extracranianas do glioblastoma multiforme (GBM) são raras devido à baixa sobrevida dos pacientes. Portanto, a história natural das metástases do GBM permanece incerta. A identificação de fatores clínicos que promovem metástases no GBM pode ajudar a elucidar os mecanismos de invasão das células tumorais no cérebro. O objetivo deste estudo foi realizar uma meta-análise avaliando a sobrevida, características, fatores prognósticos e preditores de desfechos do tratamento em pacientes com GBM metastático e descrever um caso de GBM extracraniano metastático. MÉTODOS: Relatamos o caso de uma paciente diagnosticada com GBM metastático para os pulmões e os resultados de uma meta-análise de 114 outros casos de GBM metastático identificados por meio de uma pesquisa no Medline e Bireme. RESULTADOS: A média de idade dos pacientes foi de 38,2±16,1 anos e 70,4% eram do sexo masculino. O tempo decorrido entre a identificação da metástase e o óbito foi significativamente maior em pacientes submetidos à cirurgia (p = 0,019), enquanto que o tempo do diagnóstico do tumor primário até o óbito aumentou significativamente em pacientes submetidos à radioterapia (p = 0,050). O tempo decorrido da metástase até o óbito e do diagnóstico até o óbito foi significativamente maior nos pacientes que receberam quimioterapia (p < 0,001 e p = 0,027, respectivamente). O fígado foi o local metastático associado ao menor tempo decorrido do diagnóstico até a morte (p = 0,024). CONCLUSÕES: No GBM, a ressecção cirúrgica é importante para redução do risco de metástase, e a quimioterapia e a radioterapia ajudam a prolongar a sobrevida no GBM metastático. Metástases para o fígado estão associadas a uma sobrevida mais curta quando comparadas a metástases para outros locais.

Humans , Female , Adult , Brain Neoplasms/pathology , Glioblastoma/secondary , Lung Neoplasms/secondary , Time Factors , Brain Neoplasms/mortality , Brain Neoplasms/diagnostic imaging , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Glioblastoma/mortality , Glioblastoma/diagnostic imaging , Statistics, Nonparametric , Lung Neoplasms/mortality , Lung Neoplasms/diagnostic imaging
Rev. Assoc. Med. Bras. (1992) ; 65(3): 460-468, Mar. 2019. graf
Article in English | LILACS | ID: biblio-1003053


SUMMARY INTRODUCTION: Glioblastoma (GBM) is the most frequent primary malignant tumor from the central nervous system in adults. However, the presence of systemic metastasis is an extremely rare event. The objective of this study was to review the literature, evaluating the possible biological mechanisms related to the occurrence of systemic metastasis in patients diagnosed with GBM. RESULTS: The mechanisms that may be related to GBM systemic dissemination are the blood-brain barrier breach, often seen in GBM cases, by the tumor itself or by surgical procedures, gaining access to blood and lymphatic vessels, associated with the acquisition of mesenchymal features of invasiveness, resistance to the immune mechanisms of defense and hostile environment through quiescence. CONCLUSIONS: Tumor cells must overcome many obstacles until the development of systemic metastasis. The physiologic mechanisms are not completely clear. Although not fully understood, the pathophysiological understanding of the mechanisms that may be associated with the systemic spread is salutary for a global understanding of the disease. In addition, this knowledge may be used as a basis for a therapy to be performed in patients diagnosed with GBM distant metastasis.

RESUMO INTRODUÇÃO: Glioblastoma (GBM) é o tumor maligno mais comum do sistema nervoso central em adultos. Entretanto, metástase a distância de GBM é um evento extremamente raro. O presente estudo teve o objetivo de realizar uma revisão da literatura para avaliar os possíveis mecanismos biológicos relacionados com a ocorrência de metástase a distância de pacientes com diagnóstico de GBM. RESULTADOS: Os mecanismos que podem estar relacionados com a capacidade de disseminação sistêmica do GBM são a quebra de barreira hematoencefálica (BHE) frequentemente vista em GBM, seja pela doença, seja por procedimentos cirúrgicos, dando acesso aos vasos sanguíneos e linfáticos, associada à aquisição de características mesenquimais de invasividade, resistência aos mecanismos de defesa do sistema imunológico e adaptação a hostilidades dos meios distantes por meio de quiescência. CONCLUSÕES: As células tumorais necessitam vencer diversos obstáculos até a formação de uma metástase distante. Apesar de não totalmente esclarecido, o entendimento fisiopatológico dos mecanismos pelos quais podem estar associados à disseminação sistêmica do GBM é salutar para a compreensão global da doença. Além disso, esse conhecimento pode servir de base para a terapia a ser empregada diante do paciente com diagnóstico de GBM com metástase a distância.

Humans , Central Nervous System Neoplasms/pathology , Glioblastoma/secondary , Neoplasm Metastasis/immunology , Blood-Brain Barrier/pathology , Central Nervous System Neoplasms/immunology , Glioblastoma/immunology , Immunocompetence
Article in English | WPRIM | ID: wpr-763126


PURPOSE: Glioblastoma, the most common brain tumor in adults, has poor prognosis. The purpose of this study was to determine the effect of disulfiram (DSF), an aldehyde dehydrogenase inhibitor, on in vitro radiosensitivity of glioblastoma cells with different methylation status of O⁶-methylguanine-DNA methyltransferase (MGMT) promoter and the underlying mechanism of such effect. MATERIALS AND METHODS: Five human glioblastoma cells (U138MG, T98G, U251MG, U87MG, and U373MG) and one normal human astrocyte (NHA) cell were cultured and treated with DSF or 6MV X-rays (0, 2, 4, 6, and 8 Gy). For combined treatment, cells were treated with DSF before irradiation. Surviving fractions fit from cell survival based on colony forming ability. Apoptosis, DNA damage repair, and cell cycle distributionwere assayed bywestern blot for cleaved caspase-3, γH2AX staining, and flow cytometry, respectively. RESULTS: DSF induced radiosensitization in most of the glioblastoma cells, especially, in the cells with radioresistance as wildtype unmethylated promoter (MGMT-wt), but did not in normal NHA cell. DSF augmented or induced cleavage of caspase-3 in all cells after irradiation. DSF inhibited repair of radiation-induced DNA damage in MGMT-wt cells, but not in cells with methylated MGMT promoter. DSF abrogated radiation-induced G2/M arrest in T98G and U251MG cells. CONCLUSION: Radiosensitivity of glioblastoma cells were preferentially enhanced by pre-irradiation DSF treatment compared to normal cell, especially radioresistant cells such as MGMT-wt cells. Induction of apoptosis or inhibition of DNA damage repair may underlie DSF-induced radiosensitization. Clinical benefit of combining DSF with radiotherapy should be investigated in the future.

Adult , Aldehyde Dehydrogenase , Apoptosis , Astrocytes , Brain Neoplasms , Caspase 3 , Cell Cycle , Cell Survival , Disulfiram , DNA Damage , Flow Cytometry , Glioblastoma , Humans , In Vitro Techniques , Methylation , Prognosis , Radiation Tolerance , Radiotherapy
Article in English | WPRIM | ID: wpr-763112


BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea in the past. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, developed the guideline for glioblastoma successfully and published it in Brain Tumor Research and Treatment, the official journal of KSNO, in April 2019. Recently, the KSNO guideline for World Health Organization (WHO) grade III cerebral glioma in adults has been established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searches in PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords. Scope of the disease was confined to cerebral anaplastic astrocytoma and oligodendroglioma in adults. RESULTS: Whenever radiological feature suggests high grade glioma, maximal safe resection if feasible is globally recommended. After molecular and histological examinations, patients with anaplastic astrocytoma, isocitrate dehydrogenase (IDH)-mutant should be primary treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy whereas those with anaplastic astrocytoma, NOS, and anaplastic astrocytoma, IDH-wildtype should be treated following the protocol for glioblastomas. In terms of anaplastic oligodendroglioma, IDH-mutant and 1p19q-codeletion, and anaplastic oligodendroglioma, NOS should be primary treated by standard brain radiotherapy and neoadjuvant or adjuvant PCV (procarbazine, lomustine, and vincristine) combination chemotherapy. CONCLUSION: The KSNO's guideline recommends that WHO grade III cerebral glioma of adults should be treated by maximal safe resection if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors.

Adult , Astrocytoma , Brain , Brain Neoplasms , Central Nervous System , Drug Therapy , Drug Therapy, Combination , Glioblastoma , Glioma , Humans , Isocitrate Dehydrogenase , Korea , Lomustine , Oligodendroglioma , Radiotherapy , World Health Organization