ABSTRACT
OBJECTIVE: To study the prevalence of OTX1 and OTX2 gene expression in 60 medulloblastoma specimen samples and to establish correlations between gene expression and clinical and histopathological aspects. METHODS: We performed a retrospective analysis of 60 patients with a diagnosis of medulloblastoma at the Clinicas Hospital of the School of Medicine, University of São Paulo, and the Cancer Hospital of Barretos. We created a database of the 60 patients containing information on the gene expression of OTX1 and OTX2 (obtained using real-time polymerase chain reaction) and clinical and epidemiological data. Statistical tests were performed to verify potential correlations of clinicopathological data and follow-up aspects with gene expression. RESULTS: The OTX1 gene was expressed in 52% of the study population. Expression varied with age (higher in adults), location (predominantly by hemisphere), and histological type (desmoplastic). The OTX2 gene was expressed in 62% of the study population. Expression varied with age (higher in younger age groups), location (predominantly vermis), and histological type (classic and anaplastic). A statistical correlation between OTX2 gene expression and the development of leptomeningeal metastases was observed. CONCLUSIONS: The relative expression of OTX1 and OTX2 was dependent on patient age, tumor location, and histological variant. In addition, OTX2 expression might be a predictive factor for leptomeningeal metastases of medulloblastoma. The OTX pathway should be consider as an important venue for medulloblastomas development.
Subject(s)
Cerebellar Neoplasms/genetics , Medulloblastoma/genetics , Neoplasm Proteins/genetics , Otx Transcription Factors/genetics , Adolescent , Adult , Age Factors , Brazil , Cerebellar Neoplasms/epidemiology , Cerebellar Neoplasms/therapy , Child , Child, Preschool , Female , Gene Expression Regulation, Neoplastic , Humans , Infant , Kaplan-Meier Estimate , Male , Medulloblastoma/epidemiology , Medulloblastoma/secondary , Medulloblastoma/therapy , Meningeal Neoplasms/secondary , Middle Aged , Real-Time Polymerase Chain Reaction , Retrospective Studies , Young AdultABSTRACT
OBJECTIVE: Blood-brain barrier (BBB) impairment, redistribution of pericytes, and disturbances in cerebral blood flow may contribute to the increased seizure propensity and neurological comorbidities associated with epilepsy. However, despite the growing evidence of postictal disturbances in microcirculation, it is not known how recurrent seizures influence pericytic membrane currents and subsequent vasodilation. METHODS: Here, we investigated successive changes in capillary neurovascular coupling and BBB integrity during recurrent seizures induced by 4-aminopyridine or low-Mg2+ conditions. To avoid the influence of arteriolar dilation and cerebral blood flow changes on the capillary response, we measured seizure-associated pericytic membrane currents, capillary motility, and permeability changes in a brain slice preparation. Arteriolar responses to 4-aminopyridine-induced seizures were further studied in anesthetized Sprague Dawley rats by using electrocorticography and tissue oxygen recordings simultaneously with intravital imaging of arteriolar diameter, BBB permeability, and cellular damage. RESULTS: Within the preserved vascular network in hippocampal slice cultures, pericytes regulated capillary diameter in response to vasoactive agents and neuronal activity. Seizures induced distinct patterns of membrane currents that contributed to the regulation of pericytic length. During the course of recurrent seizures, individual vasodilation responses eroded and BBB permeability increased, despite unaltered neurometabolic coupling. Reduced vascular responsiveness was associated with mitochondrial depolarization in pericytes. Subsequent capillary constriction preceded BBB opening, suggesting that pericyte injury mediates the breach in capillary integrity. In vivo findings were consistent with slice experiments, showing seizure-related neurovascular decoupling and BBB dysfunction in small cortical arterioles, accompanied by perivascular cellular injury despite normoxic conditions. SIGNIFICANCE: Our study presents a direct observation of gradually developing neurovascular decoupling during recurrent seizures and suggests pericytic injury as an inducer of vascular dysfunction in epilepsy.
Subject(s)
Blood-Brain Barrier/physiopathology , Capillaries/injuries , Capillary Permeability/physiology , Seizures/physiopathology , Animals , Brain/physiopathology , Capillaries/physiopathology , Cerebrovascular Circulation/physiology , Neurons/physiology , Neurovascular Coupling/physiology , Rats, Sprague-Dawley , Seizures/complicationsABSTRACT
Medulloblastoma is the most common childhood malignant tumor of central nervous system, but it may also occur in adults. It presents high invasive growth with spreading of tumor cells into the leptomeningeal space along the neuroaxis early in the course of the disease. Extraneural metastases are rare but frequently lethal, occurring only in 1 to 5% of patients, and are related, in the most of cases, to the presence of ventriculoperitoneal shunt. Here we characterize the clinical profile of five cases of medulloblastoma with systemic spreading of tumor cells, also comparing them to cases already described in the literature.
Subject(s)
Cerebellar Neoplasms/pathology , Medulloblastoma/secondary , Abdominal Neoplasms/secondary , Adult , Bone Marrow Neoplasms/secondary , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Lung Neoplasms/secondary , Male , Pelvic Neoplasms/secondaryABSTRACT
INTRODUÇÃO: O meduloblastoma, tumor maligno do Sistema Nervoso Central mais comum em crianças, foi inicialmente descrito de forma uniforme em 1925 por Bailey e Harvey Cushing. A despeito do avanço diagnóstico e terapêutico, os índices de morbimortalidade persistem altos. Grupos epidemiologicamente semelhantes podem ter desfechos diferentes, e evoluções desfavoráveis ocorrem em pacientes com marcadores de bom prognóstico. Os avanços nas pesquisas em biologia molecular procuram explicar os diferentes comportamentos da doença, e de forma sistemática, buscam identificar genes que sirvam como alvos terapêuticos, já que o tratamento disponível atualmente ainda é bastante insatisfatório e com muitos efeitos colaterais. Simeone e colaboradores identificaram os genes OTX1 e OTX2, presentes em humanos, e cuja função é organizar, compartimentalizar e hierarquizar a formação do sistema nervoso central, especialmente o cerebelo. Os genes OTX1 e OTX2 são expressos no tecido cerebelar em humanos até a nona semana de vida extra-uterina, exclusivamente. Os mesmos autores também identificaram que os mesmos genes são alvo terapêutico do ácido transretinóico, que inibe a expressão gênica. Estudos prévios demonstraram a expressão dos genes OTX1 e OTX2 em meduloblastomas, o que torna o ácido uma potencial terapêutica para estes tumores, assim como os genes OTX1 e OTX2 potenciais alvos para desenvolvimento de novas drogas terapêuticas. OBJETIVOS: Estudar a prevalência dos genes OTX1 e OTX2 em uma amostra de 60 pacientes, e estabelecer correlações entre a expressão gênica e aspectos clínicos, patológicos e de evolução. CASUÍSTICA E MÉTODO: Realizada análise retrospectiva de 60 pacientes com diagnóstico meduloblastoma, operados no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, e no Hospital do Câncer de Barretos. Organizado um banco de dados de 60 pacientes contendo dados da expressão gênica dos genes OTX1 e OTX2 (obtida através da técnica de PCR...
INTRODUCTION: Medulloblastoma, the most common malignant tumor of the central nervous system in children, was first uniformly described in 1925 by Bailey and Harvey Cushing. Despite the diagnostic and therapeutic advances, the morbidity and mortality rates remain high. Epidemiologically similar groups may have different outcomes, and adverse developments occur in patients with markers of good prognosis. Advances in molecular biology research seeks to explain the different behaviors of the disease, and consistently seek to identify genes that serve as drug targets, since the treatment currently available is still unsatisfactory and with many side effects. Simeone and colleagues identified genes OTX1 and OTX2 in humans, and whose function is to organize, prioritize and compartmentalize the formation of the central nervous system, especially the cerebellum. OTX1 and OTX2 genes are expressed in cerebellar tissue in humans until the ninth week of extra uterine life, exclusively. The same authors also found that the same genes are therapeutic target of trans-retinoic acid, which inhibits gene expression. Previous studies have demonstrated the expression of OTX1 and OTX2 genes in medulloblastomas, which makes the acid a potential therapy for these tumors, as well as the genes OTX2 and OTX1 potential targets for developing new therapeutic drugs. OBJECTIVES: To study the prevalence of OTX1 and OTX2 genes in a sample of 60 patients, and to establish correlations between gene expression and clinical, pathological and follow up aspects. CASUISTICS AND METHODS: A retrospective analysis of 60 patients diagnosed with medulloblastoma, assisted at Hospital of the Faculty of Medicine, University of São Paulo, and the Cancer Hospital of Barretos. Organized a database of 60 patients which contains the gene expression of OTX1 and OTX2 genes (obtained through the technique of real-time PCR) and clinical and epidemiological data. Performed statistical tests to establish a...
Subject(s)
Humans , Child , Adult , Otx Transcription Factors , SurvivalABSTRACT
Estudo retrospectivo de seis casos de abscesso de tronco cerebral, atendidos num período de cinco anos em nosso Serviço. Foram levados em consideração: idade dos pacientes, sexo, comorbidades, sorologia para HIV, quadro clínico, tratamento realizado (craniotomia ou punção por estereotaxia), microorganismo identificado e resultado do tratamento. Apresentamos, a seguir, a discussão dos casos e revisão da literatura...
Subject(s)
Male , Female , Adult , Middle Aged , Humans , Brain Abscess/surgery , Brain Abscess/diagnosis , Brain Abscess/therapy , Brain StemABSTRACT
A anastomose termino-terminal entre os segmentos esofagicos, embora constitua a melhor tecnica cirurgica para a correcao da atresia do esofago do recem-nascido, pode resultar em fistulas, deiscencias ou estenoses devidas a tensao na linha de sutura, principalmente nos casos de grande distancia entre os cotos. A miotomia circular do segmento proximal proposta por Livaditis e a manobra de alongamento mais utilizada. No presente trabalho, procurou-se verificar se esta tecnica diminui o indice de deiscencia de anastomose entre cotos esofagicos sob grande tensao e estudar se ela promove...
Subject(s)
Animals , Male , Female , Dogs , Anastomosis, Roux-en-Y , Esophageal Atresia/surgery , Wound Healing , Pilot Projects , Esophagus/surgery , Gastrointestinal TransitABSTRACT
A anastomose termino-terminal entre os segmentos esofagicos , embora constitua a melhor solucao para a atresia do esofago do recem-nascido, pode resultar em fistulas, deiscencias ou estenoses devidas a tensao na linha de sutura, principalmente nos casos de grande distancia entre os cotos. A miotomia circular do segmento proximal (manobra de Livaditis) e a tecnica de alongamento esofagico mais utilizada. No presente trabalho experimental, realizado em caes, procurou-se verificar se esta tecnica diminui o indice de deiscencia de anastomose entre cotos sob grande tensao e estudar se ela promove alteracoes morfologicas na cicatriz da anastomose...
