Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Yang, Ling. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 222-244). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Awards and Presentations --- p.ii / Abstract in English --- p.iii / Abstract in Chinese --- p.vii / Table of Contents --- p.x / List of Tables --- p.xv / List of Figures --- p.xvii / List of Abbreviations --- p.xx / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Gliomas --- p.1 / Chapter 1.1.1 --- Oligodendroglial tumors (OTs) --- p.3 / Chapter 1.1.2 --- Glioblastoma multiforme (GBM) --- p.3 / Chapter 1.1.3 --- Molecular pathology of gliomas --- p.4 / Chapter 1.1.3.1 --- Genetic alterations in OTs --- p.4 / Chapter 1.1.3.2 --- Prognostic and predictive factors in OTs --- p.7 / Chapter 1.1.3.3 --- Genetic alterations in GBM --- p.8 / Chapter 1.1.3.4 --- Prognostic and predictive factors in GBM --- p.10 / Chapter 1.2 --- microRNA(miRNA) --- p.13 / Chapter 1.2.1 --- miRNA biogenesis and function --- p.13 / Chapter 1.2.2 --- miRNA involvement in cancer --- p.17 / Chapter 1.2.2.1 --- Dysregulation of miRNAs in human malignancies --- p.17 / Chapter 1.2.2.2 --- Function and potential application of miRNAs --- p.17 / Chapter 1.2.3 --- Role of miRNAs in glioma --- p.19 / Chapter 1.2.3.1 --- miRNAs in OTs --- p.19 / Chapter 1.2.3.2 --- miRNAs in GBM --- p.20 / Chapter 1.3 --- miR-137 --- p.30 / Chapter 1.3.1 --- Biology of miR-137 --- p.30 / Chapter 1.3.2 --- Role of miR-137 in carcinogenesis --- p.33 / Chapter 1.3.2.1 --- Deregulation of miR-137 in cancer --- p.33 / Chapter 1.3.2.2 --- Regulation of miR-137 expression in cancer --- p.33 / Chapter 1.3.2.3 --- Biological functions of miR-137 in cancer --- p.37 / Chapter 1.3.3 --- Role of miR-137 in differentiation and neurogenesis --- p.39 / Chapter CHAPTER 2 --- AIMS OF STUDY --- p.43 / Chapter CHARPTER 3 --- MATERIALS AND METHODS --- p.45 / Chapter 3.1 --- Tumor samples --- p.45 / Chapter 3.2 --- Cell lines and culture conditions --- p.48 / Chapter 3.3 --- Fluorescence in situ hybridization (FISH) --- p.49 / Chapter 3.4 --- Cell transfection --- p.52 / Chapter 3.4.1 --- Transfection of oligonucleotides --- p.52 / Chapter 3.4.1.1 --- Oligonucleotide preparation --- p.52 / Chapter 3.4.1.2 --- Optimization of transfection condition --- p.52 / Chapter 3.4.2 --- Cotransfection of plasmids and miRNA mimic --- p.53 / Chapter 3.4.2.1 --- Optimization of transfection condition --- p.53 / Chapter 3.4.2.2 --- Procedure of transfection --- p.54 / Chapter 3.5 --- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) --- p.55 / Chapter 3.5.1 --- RNA extraction from frozen tissues and cell lines --- p.55 / Chapter 3.5.2 --- qRT-PCR for miR-137 --- p.56 / Chapter 3.5.3 --- qRT-PCR for CSE1L and ERBB4 transcripts --- p.57 / Chapter 3.6 --- 5-aza-2'-deoxycytidine (5-aza-dC) and Trichostatin A (TSA) treatment --- p.61 / Chapter 3.7 --- Western blotting --- p.62 / Chapter 3.7.1 --- Preparation of cell lysate --- p.62 / Chapter 3.7.2 --- Measurement of protein concentration --- p.62 / Chapter 3.7.3 --- Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) --- p.63 / Chapter 3.7.4 --- Electroblotting of proteins --- p.67 / Chapter 3.7.5 --- Immunoblotting --- p.67 / Chapter 3.8 --- Dual-luciferase reporter assay --- p.70 / Chapter 3.8.1 --- Construction of reporter plasmids --- p.70 / Chapter 3.8.1.1 --- Experimental outline --- p.70 / Chapter 3.8.1.2 --- PCR Amplification of MREs --- p.70 / Chapter 3.8.1.3 --- TA cloning --- p.71 / Chapter 3.8.1.4 --- Transformation --- p.72 / Chapter 3.8.1.5 --- Blue/white screening and validation of recombinants --- p.72 / Chapter 3.8.1.6 --- Subcloning of 3'UTR fragments into pMIR-reproter vector --- p.73 / Chapter 3.8.2 --- Site-directed mutagenesis --- p.74 / Chapter 3.8.3 --- Plasmid and miRNA mimic cotransfection --- p.76 / Chapter 3.8.4 --- Determination of luciferase activity --- p.76 / Chapter 3.9 --- Functional assays : --- p.79 / Chapter 3.9.1 --- Cell growth and proliferation assay --- p.79 / Chapter 3.9.1.1 --- "3-(4，5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay" --- p.79 / Chapter 3.9.1.2 --- Cell counting --- p.80 / Chapter 3.9.1.3 --- 5-Bromo-2'-deoxyuridine (BrdU) incorporation assay --- p.80 / Chapter 3.9.2 --- Apoptosis assay --- p.82 / Chapter 3.9.3 --- Anchorage-independent growth assay --- p.82 / Chapter 3.9.4 --- Wound healing assay --- p.83 / Chapter 3.9.5 --- Matrigel invasion assay --- p.84 / Chapter 3.9.6 --- Cell differentiation assay --- p.85 / Chapter 3.10 --- Immunohistochemical analysis --- p.86 / Chapter 3.10.1 --- H&E staining --- p.86 / Chapter 3.10.2 --- Detection of Ki-67 expression --- p.87 / Chapter 3.10.3 --- Detection of CSE1L expression --- p.87 / Chapter 3.10.4 --- Scoring methods --- p.88 / Chapter 3.11 --- Bioinformatic analysis --- p.90 / Chapter 3.12 --- Statistical analysis --- p.92 / Chapter CHAPTER 4 --- RESULTS --- p.93 / Chapter 4.1 --- Expression of miR-137 in glioma cells and clinical significance --- p.93 / Chapter 4.1.1 --- Description of 36 OT samples --- p.93 / Chapter 4.1.2 --- miR-137 level in oligodendroglial tumors and glioma cells --- p.102 / Chapter 4.1.3 --- "Association of miR-137 expression with clinicopathological features, lp/19q status and Ki-67 expression" --- p.104 / Chapter 4.2 --- miR-137 levels in glioma cells after demethylation treatment --- p.113 / Chapter 4.3 --- Biological effects of miR-137 overexpression in glioma cells --- p.118 / Chapter 4.3.1 --- Cell growth --- p.118 / Chapter 4.3.1.1 --- Cell viability --- p.118 / Chapter 4.3.1.2 --- Cell number --- p.123 / Chapter 4.3.1.3 --- Cell cycle analysis : --- p.127 / Chapter 4.3.2 --- Anchorage-independent cell growth --- p.130 / Chapter 4.3.3 --- Cell apoptosis --- p.134 / Chapter 4.3.4 --- Cell motility --- p.136 / Chapter 4.3.5 --- Cell differentiation : --- p.142 / Chapter 4.4 --- Identification of miR-137 targets --- p.144 / Chapter 4.4.1 --- In silico prediction of potential miR-137 targets --- p.144 / Chapter 4.4.2 --- Experimental validation of miR-137 targets by dual-luciferase reporter assay --- p.147 / Chapter 4.4.3 --- "Expression of miR-137 candidate targets, CSE1L and ERBB4 in glioma cells" --- p.152 / Chapter 4.4.4 --- Effects of miR-137 on CSE1L transcript and protein levels --- p.154 / Chapter 4.5 --- Expression of CSE1L in OTs --- p.156 / Chapter 4.5.1 --- CSE1L expression in OTs by qRT-PCR and IHC --- p.156 / Chapter 4.5.2 --- Correlation of CSE1L expression with clinicopathological features --- p.165 / Chapter 4.6 --- Effects of CSE1L knockdown in glioma cells --- p.168 / Chapter 4.6.1 --- Cell growth --- p.170 / Chapter 4.6.1.1 --- Cell viability --- p.170 / Chapter 4.6.1.2 --- Cell number --- p.173 / Chapter 4.6.1.3 --- Cell cycle analysis --- p.176 / Chapter 4.6.2 --- Anchorage-independent cell growth --- p.179 / Chapter 4.6.3 --- Cell apoptosis --- p.182 / Chapter 4.6.4 --- Cell motility --- p.184 / Chapter CHAPTER 5 --- DISCUSSION --- p.190 / Chapter 5.1 --- Expression of miR-137 transcript level in OTs and glioma cell lines --- p.190 / Chapter 5.2 --- Association of miR-137 expression with OT clinical and molecular parameters --- p.192 / Chapter 5.3 --- Prognostic significance of clinical features and miR-137 expression in OTs --- p.194 / Chapter 5.4 --- Inactivation mechanisms of miR-137 in glioma --- p.196 / Chapter 5.5 --- Biological effects of miR-137 overexpression in glioma cells --- p.198 / Chapter 5.6 --- CSE1L is a novel miR-137 target in glioma --- p.200 / Chapter 5.7 --- Expression of CSE1L in glioma --- p.203 / Chapter 5.8 --- Intracellular distribution of CSElL in OTs --- p.206 / Chapter 5.9 --- Correlation of CSE1L expression with clinicopathological and molecular features in OTs --- p.208 / Chapter 5.10 --- CSE1L mediates effects of miR-137 in glioma cells --- p.210 / Chapter 5.11 --- Biological roles of CSE1L in glioma cells 226}0Ø. --- p.212 / Chapter 5.11.1 --- CSE1L in glioma cell proliferation --- p.212 / Chapter 5.11.2 --- CSE1L in glioma cell apoptosis --- p.213 / Chapter 5.11.3 --- CSE1L in glioma cell invasion --- p.215 / Chapter CHAPTER 6 --- CONCLUSIONS --- p.216 / Chapter CHAPTER 7 --- FUTURE STUDIES --- p.219 / Chapter 7.1 --- Expression Molecular mechanisms for miR-137 inactivation in glioma --- p.219 / Chapter 7.2 --- Identification of more miR-137 targets in glioma --- p.219 / Chapter 7.3 --- Role of miR-137 and CSE1L in drug-induced apoptosis in glioma --- p.220 / Chapter 7.4 --- Deciphering dysregulated and clinical relevant miRNAs in glioma --- p.220 / Chapter 7.5 --- Effects of miR-137 in vivo and the therapeutic potential in glioma treatment --- p.221 / REFERENCES --- p.222

INTRODUÇÃO: As neoplasias do sistema nervoso central são frequentes nafaixa etária pediátrica e o tratamento antineoplásico pode resultar em efeitos adversos agudos ou tardios na cavidade oral. As anormalidades dentárias de forma, tamanho e número de dentes podem ocorrer se o tratamento por radioterapia de crânio e coluna, quimioterapia ou ambas forem coincidentes com a época de formação dentária em pacientes pediátricos. A gravidade das alterações depende do tipo de tratamento e da idade do paciente ao diagnóstico. OBJETIVOS: Avaliar a frequência de anormalidades dentárias em pacientes tratados para neoplasias do sistema nervoso central. MÉTODOS: Neste estudo transversal foram avaliados 31 pacientes com diagnóstico de neoplasia do sistema nervoso central que estavam fora de terapia há pelo menos um ano, comparativamente com um grupo controle composto por 31 pacientes saudáveis, pareados por idade com o grupo de estudo. As anormalidades dentárias foram avaliadas por meio de radiografias panorâmicas. RESULTADOS: A idade média ao diagnóstico dos pacientes do grupo de estudo foi de 7,3 ± 3,9 anos e as neoplasias mais frequentemente observadas foram meduloblastoma (58,1%), astrocitoma (25,8%) e ependimoma (3,2%). Não se observou diferença na frequência de anormalidades dentárias entre os grupos. As anormalidades mais frequentemente observadas nos pacientes do grupo de estudo foram microdontia (9,7%) e encurtamento radicular grau III (16,1%). Microdontia foi mais frequente em crianças que tiveram o diagnóstico antes dos 5 anos de idade, com diferença significante. Encurtamento radicular grau III foi observado em pacientes com mais de 10 anos de idade no momento do exame radiográfico, também com diferença significante. Pacientes tratados por radioterapia associada à quimioterapia apresentaram maior frequência de anormalidades dentárias, comparativamente com pacientes tratados somente por radioterapia ou quimioterapia isoladamente. Microdontia apresentou alta correlação com os dentes segundos premolares e segundos molares em pacientes tratados para neoplasias do sistema nervoso central. CONCLUSÕES: Pacientes tratados para neoplasias do sistema nervoso central apresentam alta frequência de anormalidades dentárias, porém neste estudo não houve diferença entre os grupos de estudo e controle. Microdontia foi a anormalidade dentária mais frequente em pacientes submetidos ao tratamento antineoplásico antes dos 5 anos de idade, com significância estatística. Encurtamento radicular grau III foi observado nos pacientes com mais de 10 anos de idade no momento do exame radiográfico, com diferença estatisticamente significante. Pacientes submetidos à radioterapia associada à quimioterapia apresentaram maior frequência de anormalidades dentárias / INTRODUCTION: Central nervous system neoplasms are frequent in pediatric patients and antineoplastic treatment may result in acute or late adverse effects in the oral cavity. Tooth abnormalities of shape, size and number of teeth can occur if craniospinal irradiation, drug therapy or both are coincident with the time of tooth development. Severity of these alterations depends on the type of treatment and the patient´s age at diagnosis. OBJECTIVES: To evaluate the frequency of tooth abnormalities in pediatric patients treated for central nervous system neoplasms. METHODS: This cross-sectional study assessed 31 patients with central nervous system neoplasms, who were off therapy for at least one year, comparatively with a control group of 31 healthy patients matched for age with the study group. Tooth abnormalities were evaluated by panoramic radiographs. RESULTS: Study group´s mean age at diagnosis was 7.3 ± 3.9 years and the most frequent neoplasms were medulloblastoma (58.1%), astrocytoma (25.8%) and ependyoma (3.2%). There was no difference in the frequency of tooth abnormalities between groups. The most frequently tooth abnormalities observed in the study group were microdontia (9.7%) and root shortening grade III (16.1%). Microdontia was the most common abnormality in children who were diagnosed before 5 years of age, with a significant difference. Root shortening grade III was observed in patients over 10 years of age at the time of radiographic examination, also with a significant difference. Patients treated with craniospinal irradiation combined with drug therapy presented more frequency of tooth abnormalities compared with patients treated only by craniospinal irradiation or drug therapy alone. Microdontia was highly correlated with the teeth second premolars and second molars. CONCLUSIONS: Patients treated for central nervous system neoplasms present high frequency of tooth abnormalities; however in this study there was no difference between study and control groups. Microdontia was the most frequent tooth abnormality in patients submitted to antineoplastic treatment before 5 years of age, with statistical significance. Root shortening grade III was observed in patients over 10 years of age at the time of radiographic examination, with statistically significant difference. Patients undergoing craniospinal irradiation combined with drug therapy showed high frequency of tooth abnormalities

INTRODUÇÃO: As neoplasias do sistema nervoso central são frequentes nafaixa etária pediátrica e o tratamento antineoplásico pode resultar em efeitos adversos agudos ou tardios na cavidade oral. As anormalidades dentárias de forma, tamanho e número de dentes podem ocorrer se o tratamento por radioterapia de crânio e coluna, quimioterapia ou ambas forem coincidentes com a época de formação dentária em pacientes pediátricos. A gravidade das alterações depende do tipo de tratamento e da idade do paciente ao diagnóstico. OBJETIVOS: Avaliar a frequência de anormalidades dentárias em pacientes tratados para neoplasias do sistema nervoso central. MÉTODOS: Neste estudo transversal foram avaliados 31 pacientes com diagnóstico de neoplasia do sistema nervoso central que estavam fora de terapia há pelo menos um ano, comparativamente com um grupo controle composto por 31 pacientes saudáveis, pareados por idade com o grupo de estudo. As anormalidades dentárias foram avaliadas por meio de radiografias panorâmicas. RESULTADOS: A idade média ao diagnóstico dos pacientes do grupo de estudo foi de 7,3 ± 3,9 anos e as neoplasias mais frequentemente observadas foram meduloblastoma (58,1%), astrocitoma (25,8%) e ependimoma (3,2%). Não se observou diferença na frequência de anormalidades dentárias entre os grupos. As anormalidades mais frequentemente observadas nos pacientes do grupo de estudo foram microdontia (9,7%) e encurtamento radicular grau III (16,1%). Microdontia foi mais frequente em crianças que tiveram o diagnóstico antes dos 5 anos de idade, com diferença significante. Encurtamento radicular grau III foi observado em pacientes com mais de 10 anos de idade no momento do exame radiográfico, também com diferença significante. Pacientes tratados por radioterapia associada à quimioterapia apresentaram maior frequência de anormalidades dentárias, comparativamente com pacientes tratados somente por radioterapia ou quimioterapia isoladamente. Microdontia apresentou alta correlação com os dentes segundos premolares e segundos molares em pacientes tratados para neoplasias do sistema nervoso central. CONCLUSÕES: Pacientes tratados para neoplasias do sistema nervoso central apresentam alta frequência de anormalidades dentárias, porém neste estudo não houve diferença entre os grupos de estudo e controle. Microdontia foi a anormalidade dentária mais frequente em pacientes submetidos ao tratamento antineoplásico antes dos 5 anos de idade, com significância estatística. Encurtamento radicular grau III foi observado nos pacientes com mais de 10 anos de idade no momento do exame radiográfico, com diferença estatisticamente significante. Pacientes submetidos à radioterapia associada à quimioterapia apresentaram maior frequência de anormalidades dentárias / INTRODUCTION: Central nervous system neoplasms are frequent in pediatric patients and antineoplastic treatment may result in acute or late adverse effects in the oral cavity. Tooth abnormalities of shape, size and number of teeth can occur if craniospinal irradiation, drug therapy or both are coincident with the time of tooth development. Severity of these alterations depends on the type of treatment and the patient´s age at diagnosis. OBJECTIVES: To evaluate the frequency of tooth abnormalities in pediatric patients treated for central nervous system neoplasms. METHODS: This cross-sectional study assessed 31 patients with central nervous system neoplasms, who were off therapy for at least one year, comparatively with a control group of 31 healthy patients matched for age with the study group. Tooth abnormalities were evaluated by panoramic radiographs. RESULTS: Study group´s mean age at diagnosis was 7.3 ± 3.9 years and the most frequent neoplasms were medulloblastoma (58.1%), astrocytoma (25.8%) and ependyoma (3.2%). There was no difference in the frequency of tooth abnormalities between groups. The most frequently tooth abnormalities observed in the study group were microdontia (9.7%) and root shortening grade III (16.1%). Microdontia was the most common abnormality in children who were diagnosed before 5 years of age, with a significant difference. Root shortening grade III was observed in patients over 10 years of age at the time of radiographic examination, also with a significant difference. Patients treated with craniospinal irradiation combined with drug therapy presented more frequency of tooth abnormalities compared with patients treated only by craniospinal irradiation or drug therapy alone. Microdontia was highly correlated with the teeth second premolars and second molars. CONCLUSIONS: Patients treated for central nervous system neoplasms present high frequency of tooth abnormalities; however in this study there was no difference between study and control groups. Microdontia was the most frequent tooth abnormality in patients submitted to antineoplastic treatment before 5 years of age, with statistical significance. Root shortening grade III was observed in patients over 10 years of age at the time of radiographic examination, with statistically significant difference. Patients undergoing craniospinal irradiation combined with drug therapy showed high frequency of tooth abnormalities

Orientador: Helder Tedeschi / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T19:44:14Z (GMT). No. of bitstreams: 1 Valadares_MarceloGomesCordeiro_M.pdf: 1238842 bytes, checksum: f4f19f2521d318218d181dd5e357d746 (MD5) Previous issue date: 2015 / Resumo: Introdução: O tratamento para gliomas de alto grau consiste em cirurgia seguida de radioterapia e quimioterapia. Mesmo com o melhor tratamento disponível a sobrevida em geral não atinge 2 anos para glioblastoma multiforme e 2 a 5 anos para outros gliomas anaplásicos. Estudos realizados em países em desenvolvimento sugerem que as limitações financeiras dos sistemas públicos de saúde destes países podem dificultar o acesso da população aos recursos necessários, podendo inclusive influenciar negativamente a sobrevida. Neste trabalho analisamos uma série de pacientes portadores de gliomas de alto grau tratados em um hospital público de uma grande região metropolitana brasileira. Comparamos o tratamento oferecido com o preconizado na literatura e verificamos se eventuais limitações nas diversas etapas do tratamento multidisciplinar afetam a qualidade do serviço prestado. Método: Analisamos retrospectivamente prontuários de pacientes portadores de gliomas de alto grau tratados no Hospital de Clínicas da Unicamp entre 2007 e 2013. Resultados: Foram incluídos 135 pacientes. A idade média foi de 57 anos e 2 meses e haviam 2 homens para cada mulher. A unidade de emergência foi a porta de entrada para 89% dos pacientes. No momento do diagnóstico 90.3% já apresentavam sintomas há mais de 2 semanas e 14,8% estavam sintomáticos há mais de 12 semanas. Quimioterapia e radioterapia foram prescritas para 56% dos pacientes. Radioterapia apenas foi o tratamento de escolha para 25% e outros 19% foram encaminhados para cuidados paliativos. Tromboembolismo venoso foi diagnosticado em 26%, infecções relacionadas ao procedimento cirúrgico em 16%. Após a cirurgia a mediana de tempo para início dos tratamentos subsequentes foi: 6.71 semanas para a primeira consulta com o radioterapêuta, 6.28 semanas para a primeira consulta com o oncologista e 12.57 semanas para iniciar a quimioterapia e radioterapia. Progressão tumoral com necessidade de nova abordagem cirúrgica foi observada em 27 pacientes no grupo de terapia tardia (>6 semanas) e em nenhum paciente no grupo de terapia precoce (?6 semanas) (p=0.002). Não foi observada correlação estatística entre a ocorrência de eventos tromboembólicos (p=0.09) ou infecciosos (p=0.057) e a demora para o início do tratamento adjuvante. A mediana de sobrevida de 100 pacientes portadores de glioblastoma multiforme submetidos a todas as formas de tratamento foi de 7.8 meses. Conclusão: Embora o tratamento cirúrgico seguido de radioterapia e quimioterapia esteja disponível no Hospital de Clínicas da Unicamp, apenas 56% dos pacientes são submetidos a todo o tratamento preconizado e apenas 12% iniciam a quimioterapia e radioterapia em menos de 6 semanas após a cirurgia. Estes números são inferiores aos observados em países desenvolvidos, mas compatíveis com outros estudos de países em desenvolvimento. A mesma comparação é feita em relação à sobrevida global dos pacientes diagnosticados com glioblastoma multiforme. Os dados apresentados reforçam a tese de que o tratamento de portadores de gliomas de alto grau é influenciado negativamente pelas limitações presentes na saúde pública de países em desenvolvimento / Abstract: Introduction: The general management of high-grade gliomas is based on surgery plus radiotherapy and chemotherapy. However, in developing countries, the lack of financial resources may delay the treatment, and probably affect patients¿ outcome. Based on this, the aim of this study is to review the clinical data of high-grade glioma patients treated in a brazilian referral public hospital. Methods: We retrospectively analyzed the clinical data with emphasis on the management options (surgery, radiotherapy and chemotherapy) of high grade glioma patients from 2007 to 2014 at the University of Campinas (Unicamp) hospital. Results: A total of 135 patients (27% of all brain tumors) had the diagnosis of high-grade glioma and were included. The mean age of high-grade glioma patients at the time of diagnosis was 57 years and 2 months. There were 90 men (67%) and 44 women (33%). The outpatient referral system was responsible for only 15 (11%) admissions with 120 (89%) patients being admitted through the emergency unit. Headache was the main complaint and 90.3% of the patients had been symptomatic for over 2 weeks and 14,8% for over 12 weeks. After surgery 56% were treated with chemotherapy and radiotherapy. Radiotherapy was the single therapy for 25% of the cases. Another 19% were referred to supportive care. After surgery patients took a median 6.71 weeks to the first radiotherapy consultation, 6.28 weeks to the first clinical oncology consultation and a median 12.57 weeks to start radiation. Only 12% started radiation in less than 6 weeks. Tumor progression requiring a second surgery was observed in 27 patients in the delayed therapy group (> 6weeks) compared with no patients in the early therapy (< 6 weeks) group (P=.002). Glioblastoma Multiforme patients overall survival was 7.8 months. Conclusion: Although surgery, radiation and temozolamide were available at our institution only 56% of the patients received all these treatments and only 12% started radiation in less than 6 weeks. These numbers fail in comparison to many studies published in developed countries but are similar to others published in developing nations. The same applies to the overall survival calculated for glioblastoma patients. This study supports that financial constrictions in public health care in developing countries have a negative impact on high-grade glioma treatment / Mestrado / Neurologia / Mestre em Ciências Médicas