RESUMO
INTRODUCTION: Hydrocephaly is a disease that affects not only the dynamics of the cerebrospinal fluid, but also other structures of the central nervous system. Although shunt is effective in reducing ventriculomegaly, many neurological damages are not reversed with surgery. Several studies demonstrate that oxidative stress is involved in the genesis of hydrocephalus lesions. OBJECTIVE: Evaluate the neuroprotective response of quercetin in hydrocephalus. MATERIALS AND METHODS: Male newborns rats were used, which received the 15% kaolin injection in the cisterna magna for induction of hydrocephalus. They were divided into control group (C), untreated hydrocephalic (HN), shunted hydrocephalic (HD), hydrocephalic treated with distilled water (HA), hydrocephalic treated with distilled water and shunt (HDA), hydrocephalic treated with quercetin peritoneal (HQp), hydrocephalic treated with quercetin peritoneal and shunt (HDQp), hydrocephalic treated with quercetin by gavage (HQg), and hydrocephalus treated with quercetin by gavage and shunt (HDQg). RESULTS: Quercetin significantly improved the immunohistochemical markers, mainly caspase and GFAP. There were no significant changes in clinical/behavioral assessment. The use of isolated quercetin does not alter the volume and ventricular size, and the realization of ventriculo-subcutaneous shunt in newborn rats with hydrocephalus presents a high morbi-mortality. CONCLUSION: The use of quercetin shows laboratory improvement of the effects of glial lesion and corpus callosum fibers and is therefore not justified by the use of the routine substance as neuroprotective.
Assuntos
Encéfalo/efeitos dos fármacos , Hidrocefalia/patologia , Fármacos Neuroprotetores/farmacologia , Quercetina/farmacologia , Animais , Antioxidantes/farmacologia , Encéfalo/patologia , Modelos Animais de Doenças , Masculino , RatosRESUMO
In pituitary tumors, P27(CDKN1B) is underexpressed. We aimed to clarify whether translational regulation underlies this phenomenon. This study evaluated the expression of P27/CDKN1B, its targets (CCNE1, CDK2) and translational regulators (DKC1, RPS13, miR221, miR222) and screened for DKC1 variants in sporadic pituitary adenomas. Samples were obtained during transsphenoidal surgery from 48 patients with pituitary adenomas: 10 ACTH-, 17 GH-secreting, and 21 nonfunctioning (NFPA). The control group comprised 7 normal pituitaries (NP) obtained during autopsies. Gene expression was assessed by RT-PCR and protein expression by immunohistochemistry. The 15 exons of DKC1 were sequenced. P27 protein underexpression was observed in all adenomas subtypes (p=0.001). CCNE1 mRNA (p=0.01) overexpression, but not protein, was observed in NFPA. No differential gene expression among groups was observed in CDKN1B regulators RPS13 (p=0.23) and DKC1 (p=0.34). The expression of miR221 and miR222 was similar among tumors and NP. Frequent DKC1 variants (SNPs) were found in exon 14 and in the 3'-UTR in similar frequency to NCBI-dsSNP databases. We also observed rare DKC1 variants in 11% of the studied tumor samples, indicating a high prevalence in pituitary adenomas, however, in silico studies failed to indicate deleterious effects. The high frequency of DKC1 variants may influence, in some extent, pituitary tumors development, without clear role in its tumorigenesis. Our data reinforce the P27 underexpression in pituitary adenomas and provide further evidence of the post-translational machinery involvement, although this phenomenon cannot be explained either by mis-expression of P27 translational regulators - DKC1, RPS13, miR221, miR222 - or directly by DKC1 mutations.
Assuntos
Carcinogênese/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Neoplasias Hipofisárias/metabolismo , Biossíntese de Proteínas , Sequência de Bases , Carcinogênese/patologia , Proteínas de Ciclo Celular/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Hipófise/metabolismo , Hipófise/patologia , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Padrões de ReferênciaRESUMO
PURPOSE: Telomere dysfunction and telomerase activation underlie cancer transformation. This study aims to investigate the contribution of telomere biology to pituitary tumor behavior. SUBJECTS AND METHODS: Samples from 50 patients with pituitary tumors (11 ACTH-secreting, 18 GH-secreting, and 21 non-secreting tumors) and 7 subjects without pituitary lesions were collected. The expressions of telomerase essential components TERT and TERC and tumor telomere content were measured by quantitative PCR techniques. RESULTS: Telomerase (TERT) expression was detected in 36% of tumors. No correlation was observed between TERT and TERC expression level and tumor size in any tumor type. There was no association between gene expression and clinical findings. Telomere content (T/S ratio) was similar between pituitary adenomas (0.39 ± 0.16) and normal pituitaries (0.47 ± 0.12; p = 0.24) and also was between the different adenoma types: ACTH-secreting (0.43 ± 0.08), GH-secreting (0.31 ± 0.12), and non-secreting (0.42 ± 0.20; p = 0.10) tumors. CONCLUSIONS: The telomere content and expression of telomerase components are comparable between normal pituitary glands and tumor tissues, suggesting that telomere biology does not play an important role in pituitary tumor development.
Assuntos
Expressão Gênica/fisiologia , Neoplasias Hipofisárias/metabolismo , Telomerase/metabolismo , Telômero/metabolismo , Adulto , Humanos , Pessoa de Meia-Idade , Neoplasias Hipofisárias/enzimologia , RNA/metabolismoRESUMO
Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98 th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL). In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence.
Assuntos
Cerebelo/metabolismo , Miosina Tipo V/metabolismo , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Cadáver , Criança , Pré-Escolar , Eletroforese em Gel de Ágar , Feminino , Humanos , Immunoblotting , Imuno-Histoquímica , Lactente , Recém-Nascido , Masculino , Adulto JovemRESUMO
Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL). In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence.
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Adulto Jovem , Cerebelo/metabolismo , Miosina Tipo V/metabolismo , Fatores Etários , Cadáver , Eletroforese em Gel de Ágar , Immunoblotting , Imuno-HistoquímicaRESUMO
Febrile seizures (FS) affect almost 2-5 percent of children and factors related to an increase susceptibility of children to FS may involve an imbalance of inflammatory cytokines and genetic factors. FS had low morbidity, but may be associated with the occurrence of late chronic epilepsy. Here we describe factors related to FS and its possible correlation with SUDEP.
Crises febris (CF) afetam aproximadamente 2-5 por cento das crianças e os fatores envolvidos com essa maior susceptibilidade das crianças às CF podem estar relacionados com uma ação inadequada de citocinas inflamatórias, além de fatores genéticos. As CF têm baixa morbidade, mas podem estar associadas à ocorrência de epilepsia crônica. Nós discutiremos os fatores relacionados com CF, considerando-se sua possível associação com SUDEP.
Assuntos
Criança , Humanos , Morte Súbita/etiologia , Epilepsia/complicações , Convulsões Febris/complicaçõesRESUMO
People with epilepsy have an increased risk of dying prematurely and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). SUDEP is mainly a problem for patients with chronic uncontrolled epilepsy. The ultimate goal of research in SUDEP is to develop new methods to prevent it and actions other than medical and surgical therapies that could be very useful. Nutritional aspects, i.e., omega-3 fatty acids deficiency, could have an interesting role in this scenario. Some animal and clinical studies have suggested that omega-3 fatty acids could be useful in the prevention and treatment of epilepsy and hence SUDEP. It has been ascertained that the only foods that provide large amounts of omega-3 are seafood (fish and shellfish); however, some fish are contaminated with methylmercury, which may counteract the positive effects of omega-3 fatty acids. Our update review summarises the knowledge of the role of fish consumption on epilepsy research.
Assuntos
Morte Súbita/etiologia , Morte Súbita/prevenção & controle , Suplementos Nutricionais , Epilepsia/complicações , Ácidos Graxos Ômega-3/administração & dosagem , Produtos Pesqueiros/análise , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Humanos , Compostos de Metilmercúrio/análiseRESUMO
People with epilepsy have an increased risk of dying prematurely and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). SUDEP is mainly a problem for patients with chronic uncontrolled epilepsy. The ultimate goal of research in SUDEP is to develop new methods to prevent it and actions other than medical and surgical therapies that could be very useful. Nutritional aspects, i.e., omega-3 fatty acids deficiency, could have an interesting role in this scenario. Some animal and clinical studies have suggested that omega-3 fatty acids could be useful in the prevention and treatment of epilepsy and hence SUDEP. It has been ascertained that the only foods that provide large amounts of omega-3 are seafood (fish and shellfish); however, some fish are contaminated with methylmercury, which may counteract the positive effects of omega-3 fatty acids. Our update review summarises the knowledge of the role of fish consumption on epilepsy research.
Pessoas com epilepsia têm um risco aumentado de morrer de forma prematura e a causa mais comum de morte relacionada à epilepsia encontra-se na categoria de morte súbita inesperada em epilepsia (SUDEP). SUDEP é um problema significativo para pacientes com epilepsia crônica não controlada. O principal objetivo nas pesquisas em SUDEP é o desenvolvimento de métodos capazes de levar à sua prevenção e ações outras que não medicamentosas e cirúrgicas que podem ser úteis. Os aspectos nutricionais, como por exemplo, a deficiência do ácido graxo ômega-3 pode ter um papel interessante neste cenário. Alguns estudos animais e clínicos têm sugerido que os ácidos graxos ômega-3 podem ser úteis na prevenção e no tratamento da epilepsia e, consequentemente, na SUDEP. Os únicos alimentos que contêm grandes proporções de ômega-3 são os frutos do mar (peixes e mariscos). No entanto, alguns peixes podem estar contaminados com metilmercúrio, o que pode levar a um efeito contrário ao benefício trazido pelos ácidos graxos ômega-3. Aqui, resumimos o conhecimento do papel do consumo de peixe nas pesquisas em epilepsia.
Assuntos
Humanos , Suplementos Nutricionais , Morte Súbita/etiologia , Morte Súbita/prevenção & controle , Epilepsia/complicações , /administração & dosagem , Produtos Pesqueiros/análise , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Compostos de Metilmercúrio/análiseRESUMO
People with epilepsy have an increased risk of dying prematurely and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). SUDEP is mainly a problem for patients with chronic uncontrolled epilepsy. The ultimate goal of research in SUDEP is to develop new methods to prevent it and actions other than medical and surgical therapies that could be very useful. Nutritional aspects, i.e., omega-3 fatty acids deficiency, could have an interesting role in this scenario. Some animal and clinical studies have suggested that omega-3 fatty acids could be useful in the prevention and treatment of epilepsy and hence SUDEP. It has been ascertained that the only foods that provide large amounts of omega-3 are seafood (fish and shellfish); however, some fish are contaminated with methylmercury, which may counteract the positive effects of omega-3 fatty acids. Our update review summarises the knowledge of the role of fish consumption on epilepsy research.(AU)
Pessoas com epilepsia têm um risco aumentado de morrer de forma prematura e a causa mais comum de morte relacionada à epilepsia encontra-se na categoria de morte súbita inesperada em epilepsia (SUDEP). SUDEP é um problema significativo para pacientes com epilepsia crônica não controlada. O principal objetivo nas pesquisas em SUDEP é o desenvolvimento de métodos capazes de levar à sua prevenção e ações outras que não medicamentosas e cirúrgicas que podem ser úteis. Os aspectos nutricionais, como por exemplo, a deficiência do ácido graxo ômega-3 pode ter um papel interessante neste cenário. Alguns estudos animais e clínicos têm sugerido que os ácidos graxos ômega-3 podem ser úteis na prevenção e no tratamento da epilepsia e, consequentemente, na SUDEP. Os únicos alimentos que contêm grandes proporções de ômega-3 são os frutos do mar (peixes e mariscos). No entanto, alguns peixes podem estar contaminados com metilmercúrio, o que pode levar a um efeito contrário ao benefício trazido pelos ácidos graxos ômega-3. Aqui, resumimos o conhecimento do papel do consumo de peixe nas pesquisas em epilepsia.(AU)
Assuntos
Ingestão de Alimentos/normas , Peixes/classificação , Epilepsia/dietoterapia , Ácidos Graxos Ômega-3/administração & dosagem , Coração , Produtos Pesqueiros/toxicidade , Ácidos Graxos Ômega-3/uso terapêutico , Ácidos Graxos Insaturados/uso terapêuticoRESUMO
Biochemical markers for remission on acromegaly activity are controversial. We studied a subset of treated acromegalic patients with discordant nadir GH levels after oral glucose tolerance test (oGTT) and IGF-I values to refine the current consensus on acromegaly remission. We also compared GH results by two GH immunoassays. From a cohort of 75 treated acromegalic patients, we studied 13 patients who presented an elevated IGF-I despite post-oGTT nadir GH of < or =1 microg/l. The 12-h daytime GH profile (GH-12 h), nadir GH after oGTT, and basal IGF-I levels were studied in patients and controls. Bland-Altman method showed high concordance between GH assays. Acromegalic patients showed higher mean GH-12 h values (0.71+/-0.36 vs. 0.31+/-0.28 microg/l; p<0.05) and nadir GH after oGTT (0.48+/-0.32 vs. 0.097+/-0.002 microg/l; p<0.05) as compared to controls. Nadir GH correlated with mean GH-12 h (r=0.92, p<0.05). The mean GH-12 h value from upper 95% CI of controls (0.54 microg/l) would correspond to a theoretical normal nadir GH of < or =0.27 microg/l. Patients with GH nadir < or =0.3 microg/l had IGF-I between 100-130% ULNR (percentage of upper limit of normal range) and mean GH-12 h of 0.35+/-0.15, and patients with GH nadir >0.3 and < or =1 microg/l had IGF-I >130% ULNR and mean GH-12 h of 0.93+/-0.24 microg/l. Our data integrate daytime GH secretion, nadir GH after oGTT, and plasma IGF-I concentrations showing a continuum of mild residual activity in a subgroup of treated acromegaly with nadir GH values < or =1 microg/l. The degree of increased IGF-I levels and nadir GH after oGTT are correlated with the subtle abnormalities of daytime GH secretion.
Assuntos
Acromegalia/metabolismo , Hormônio do Crescimento Humano/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Acromegalia/radioterapia , Acromegalia/cirurgia , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Glucose/metabolismo , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Moyamoya disease (MMD) is an uncommon cerebrovascular disorder characterized by progressive stenosis of the terminal portion of the internal carotid artery and its main branches. Direct and indirect bypass techniques have been devised with the aim of promoting neoangiogenesis. The current study aimed to investigate the role of multiple cranial burr hole (MCBH) operations in the prevention of cerebral ischemic attacks in children with MMD. Seven children suffering from progressive MMD were submitted to the MCBH and arachnoid opening technique. Ten to 20 burr holes were drilled in the fronto-temporo-parieto-occipital area of each hemisphere in each patient, depending on the site and extent of the disease. All patients were evaluated pre- and postoperatively by means of Barthel index (BI), CT, MR, angio-MR, and angiography. Patients had no recurrence of ischemic attacks postoperatively. Neoangiogenesis was observed in both hemispheres. One patient developed a persistent subdural collection after surgery, thus requiring placement of a subdural-peritoneal shunt. Postoperative BI was statistically significantly improved (P=0.02). This report suggests that MCBH for revascularization in MMD is a simple procedure with a relatively low risk of complications and effective for preventing cerebral ischemic attacks in children. In addition, MCBH may be placed as an adjunct to other treatments for MMD.
Assuntos
Revascularização Cerebral/métodos , Ataque Isquêmico Transitório/etiologia , Ataque Isquêmico Transitório/prevenção & controle , Doença de Moyamoya/cirurgia , Trepanação/métodos , Adolescente , Criança , Pré-Escolar , Craniotomia/métodos , Feminino , Humanos , Angiografia por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Doença de Moyamoya/complicações , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
Cadherins are cell-to-cell adhesion molecules that play an important role in the establishment of adherent-type junctions by mediating calcium-dependent cellular interactions. The CDH1 gene encodes the transmembrane glycoprotein E-cadherin which is important in maintaining homophilic cell-cell adhesion in epithelial tissues. E-cadherin interacts with catenin proteins to maintain tissue architecture. Structural defects or loss of expression of E-cadherin have been reported as a common feature in several human cancer types. This study aimed to evaluate the expression of E-cadherin and their correlation with clinical features in microdissected brain tumor samples from 81 patients, divided into 62 astrocytic tumors grades I to IV and 19 medulloblastomas, and from 5 white matter non-neoplasic brain tissue samples. E-cadherin (CDH1) gene expression was analyzed by quantitative real-time polymerase chain reaction. Mann-Whitney, Kruskal-Wallis, Kaplan-Meir, and log-rank tests were performed for statistical analyses. We observed a decrease in expression among pathological grades of neuroepithelial tumors. Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than did neuroepithelial tumors. Expression of E-cadherin gene was higher in astrocytic than embryonal tumors (P = 0.0168). Low-grade malignancy astrocytomas (grades I-II) showed higher CDH1 expression than did high-grade malignancy astrocytomas (grades III-IV) and medulloblastomas (P < 0.0001). Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than grade I malignancy astrocytomas, considered as benign tumors (P = 0.0473). These results suggest that a decrease in E-cadherin gene expression level in high-grade neuroepithelial tumors may be a hallmark of malignancy in dedifferentiated tumors and that it may be possibly correlated with their progression and dissemination.
Assuntos
Caderinas/genética , Perfilação da Expressão Gênica , Neoplasias Neuroepiteliomatosas/genética , Adolescente , Adulto , Encéfalo/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Neoplasias Neuroepiteliomatosas/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
INTRODUCTION: Maternal folic acid deficiency is the most important metabolic factor in the etiology of neural tube defects (NTD) and is reduced by ethanol, which is extensively consumed by young women. OBJECTIVE: The objective of the study was to determine whether folic acid supplementation in dietary saccharose is efficient in the prevention NTD induced by ethanol in fetuses of Swiss mice. MATERIALS AND METHODS: Pregnant mice were divided into four groups of six animals each: control (C), ethanol (E), deficient-supplemented (DS), and deficient-supplemented + ethanol (DSE). Groups C and E received commercial mouse chow (containing 3 mg/kg folic acid) throughout the experiment, while groups DS and DSE received a folic acid-free diet with the addition of saccharose supplemented with folic acid (2 mg/kg folic acid) in water. Group E and DSE animals received ethanol (4 g/kg) administered intraperitoneally from the seventh to the ninth gestational day (gd) and were euthanized on the 18th gd, while groups C and DS received saline. RESULTS: Congenital anomalies were observed in groups E and DSE. The fetal weight and length of the animals in group E were lower than in groups C and DS and, in group DSE, were lower than in groups C and DS. The placental diameter of group E was smaller than that of group C, and the placental weight of group C animals was lower than that of groups E, DSE, and DS. CONCLUSION: The study demonstrated that dietary supplementation with folate in saccharose is an accessible means of consumption that could be further diffused but in an increased dose than recommended to reduce the teratogenic effects of ethanol.
Assuntos
Anormalidades Induzidas por Medicamentos/prevenção & controle , Etanol/toxicidade , Ácido Fólico/uso terapêutico , Sacarose/química , Administração Oral , Animais , Depressores do Sistema Nervoso Central/administração & dosagem , Depressores do Sistema Nervoso Central/toxicidade , Suplementos Nutricionais , Etanol/administração & dosagem , Feminino , Retardo do Crescimento Fetal/induzido quimicamente , Retardo do Crescimento Fetal/prevenção & controle , Peso Fetal/efeitos dos fármacos , Ácido Fólico/administração & dosagem , Ácido Fólico/química , Idade Gestacional , Injeções Intraperitoneais , Masculino , Exposição Materna , Camundongos , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/prevenção & controle , Gravidez , Resultado da Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/prevenção & controleRESUMO
Cadherins are cell-to-cell adhesion molecules that play an important role in the establishment of adherent-type junctions by mediating calcium-dependent cellular interactions. The CDH1 gene encodes the transmembrane glycoprotein E-cadherin which is important in maintaining homophilic cell-cell adhesion in epithelial tissues. E-cadherin interacts with catenin proteins to maintain tissue architecture. Structural defects or loss of expression of E-cadherin have been reported as a common feature in several human cancer types. This study aimed to evaluate the expression of E-cadherin and their correlation with clinical features in microdissected brain tumor samples from 81 patients, divided into 62 astrocytic tumors grades I to IV and 19 medulloblastomas, and from 5 white matter non-neoplasic brain tissue samples. E-cadherin (CDH1) gene expression was analyzed by quantitative real-time polymerase chain reaction. Mann-Whitney, Kruskal-Wallis, Kaplan-Meir, and log-rank tests were performed for statistical analyses. We observed a decrease in expression among pathological grades of neuroepithelial tumors. Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than did neuroepithelial tumors. Expression of E-cadherin gene was higher in astrocytic than embryonal tumors (P = 0.0168). Low-grade malignancy astrocytomas (grades I-II) showed higher CDH1 expression than did high-grade malignancy astrocytomas (grades III-IV) and medulloblastomas (P < 0.0001). Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than grade I malignancy astrocytomas, considered as benign tumors (P = 0.0473). These results suggest that a decrease in E-cadherin gene expression level in high-grade neuroepithelial tumors may be a hallmark of malignancy in dedifferentiated tumors and that it may be possibly correlated with their progression and dissemination.
Assuntos
Humanos , Adolescente , Adulto , Pessoa de Meia-Idade , Caderinas/genética , Perfilação da Expressão Gênica , Neoplasias Neuroepiteliomatosas/genética , Cérebro/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Neuroepiteliomatosas/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
The advances in the cure rates observed in the oncology field in the past decades were not fully assembled by primary brain tumors. In this heterogeneous group of diseases, resistance to either chemotherapy or radiotherapy still is a major problem to be addressed. Several genetic and epigenetic events may directly influence the response to treatment in these tumors. Throughout recent discoveries, drug resistance in brain tumors was better understood as a final product of different and complexes pathways that interact and modulate cell performance to treatment. The last years experienced a new paradigm in the way brain tumor drug-resistance genes are elected out of the vast human genomic universe. In the former era, models of cell resistance that were documented on solid tumors other than brain were investigated at the central nervous system's counterpart. Nowadays, genomic-based hypothesis generation, supported by modern genetic technique tolls, seem effective in revealing new candidate-genes that might confer the resistance phenotype. Nevertheless, new treatment approaches and novel drugs based on the pharmacogenomic resistance profile, particularly for brain tumors, are just starting to become a reality for clinical purposes.
Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Resistencia a Medicamentos Antineoplásicos/genética , Epigênese Genética/genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/prevenção & controle , Epigênese Genética/efeitos dos fármacos , Predisposição Genética para Doença/genética , HumanosRESUMO
We describe the relative frequency, clinical features, neuroimaging and pathological results, and outcome after pharmacological or surgical intervention for a series of pediatric patients with temporal lobe epilepsy (TLE) from an epilepsy center in Brazil. The medical records of children younger than 12 years with features strongly suggestive of TLE were reviewed from January 1999 to June 1999. Selected children were evaluated regarding clinical, EEG, and magnetic resonance imaging (MRI) investigation and divided into three groups according to MRI: group 1 (G1, N = 9), patients with hippocampal atrophy; group 2 (G2, N = 10), patients with normal MRI, and group 3 (G3, N = 12), patients with other specific temporal lesions. A review of 1732 records of children with epilepsy revealed 31 cases with TLE (relative frequency of 1.79 percent). However, when the investigation was narrowed to cases with intractable seizures that needed video-EEG monitoring (N = 68) or epilepsy surgery (N = 32), the relative frequency of TLE increased to 19.11 (13/68) and 31.25 percent (10/32), respectively. At the beginning of the study, 25 of 31 patients had a high seizure frequency (80.6 percent), which declined to 11 of 31 (35.5 percent) at the conclusion of the study, as a consequence of pharmacological and/or surgical therapy. This improvement in seizure control was significant in G1 (P < 0.05) and G3 (P < 0.01) mainly due to good postsurgical outcome, and was not significant in G2 (P > 0.1, McNemar's test). These results indicate that the relative frequency of TLE in children was low, but increased considerably among cases with pharmacoresistant seizures. Patients with specific lesions were likely to undergo surgery, with good postoperative outcomes.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Epilepsia do Lobo Temporal/cirurgia , Hipocampo/patologia , Lobo Temporal/patologia , Atrofia , Eletroencefalografia/métodos , Imageamento por Ressonância Magnética , Período Pós-Operatório , Estudos Retrospectivos , Resultado do Tratamento , Gravação em VídeoRESUMO
We describe the relative frequency, clinical features, neuroimaging and pathological results, and outcome after pharmacological or surgical intervention for a series of pediatric patients with temporal lobe epilepsy (TLE) from an epilepsy center in Brazil. The medical records of children younger than 12 years with features strongly suggestive of TLE were reviewed from January 1999 to June 1999. Selected children were evaluated regarding clinical, EEG, and magnetic resonance imaging (MRI) investigation and divided into three groups according to MRI: group 1 (G1, N = 9), patients with hippocampal atrophy; group 2 (G2, N = 10), patients with normal MRI, and group 3 (G3, N = 12), patients with other specific temporal lesions. A review of 1732 records of children with epilepsy revealed 31 cases with TLE (relative frequency of 1.79%). However, when the investigation was narrowed to cases with intractable seizures that needed video-EEG monitoring (N = 68) or epilepsy surgery (N = 32), the relative frequency of TLE increased to 19.11 (13/68) and 31.25% (10/32), respectively. At the beginning of the study, 25 of 31 patients had a high seizure frequency (80.6%), which declined to 11 of 31 (35.5%) at the conclusion of the study, as a consequence of pharmacological and/or surgical therapy. This improvement in seizure control was significant in G1 (P < 0.05) and G3 (P < 0.01) mainly due to good postsurgical outcome, and was not significant in G2 (P > 0.1, McNemar's test). These results indicate that the relative frequency of TLE in children was low, but increased considerably among cases with pharmacoresistant seizures. Patients with specific lesions were likely to undergo surgery, with good postoperative outcomes.
Assuntos
Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Lobo Temporal/patologia , Atrofia , Criança , Pré-Escolar , Eletroencefalografia/métodos , Epilepsia do Lobo Temporal/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Período Pós-Operatório , Estudos Retrospectivos , Resultado do Tratamento , Gravação em VídeoRESUMO
BACKGROUND: Although neuroimage and surgical techniques have improved substantially, the prognosis of patients with astrocytic tumors remains unchanged. The purpose of this study was to evaluate the proliferative activity in astrocytic tumors in different grades of malignancy and correlate it to other clinical features. PATIENTS AND METHODS: From archival paraffin-embedded surgical specimens of 40 patients of the Ribeirão Preto Medical School with World Health Organization grade II (n = 10), grade III (n = 5) and grade IV astrocytomas (n = 25), the MIB-1 labeling index (LI) was determined using at least a half of the blocks per case. The results were correlated to the biological behavior of the tumors. The aims of this study were to determine the level of MIB-1 LI values (cut-off) that reflect differences in biological behavior of these tumors, the impact on survival of clinical features such as age, tumor location or extension of surgical removal as well as the adjuvant therapy. RESULTS AND CONCLUSIONS: As expected, a wide range of MIB-1 LI values was disclosed (mean of 2.35% in grade II astrocytomas to 12.28% in glioblastomas). A close relationship was found between MIB-1 LI and survival of patients with astrocytomas according to the histological grade. All but 1 recurrent tumor presented higher MIB-1 LI in the second biopsy, and the mean MIB-1 LI of the patients who died in the immediate postoperative period (n = 7) was higher in comparison to the MIB-1 LI of the respective grade. Postoperative radiation therapy was an important factor that affected the survival of patients with high-grade astrocytomas (p = 0.006). MIB-1 LI cut-off of 3% divided the astrocytomas in 2 groups with significantly different survival (p < 0.001): median survival time of 12 months (low-grade) versus 45 months (high-grade). On the other hand, univariate analysis did not show any correlation between survival and extension of surgical resection (radical versus partial), tumor's location or patient's age at surgery.
Assuntos
Astrocitoma/metabolismo , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/metabolismo , Antígeno Ki-67/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Astrocitoma/mortalidade , Astrocitoma/patologia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Valores de Referência , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Studies in animals lacking the cellular prion protein (PrP(c)) gene (Prnp) showed higher neuronal excitability in vitro and increased sensitivity to seizures in vivo. The authors previously reported a rare polymorphism at codon 171 (Asn-->Ser) of human Prnp to be associated with mesial temporal lobe epilepsy related to hippocampal sclerosis. They demonstrated that the same variant allele is also associated with symptomatic epilepsies related to different forms of malformations of cortical development.
Assuntos
Substituição de Aminoácidos , Amiloide/genética , Córtex Cerebral/anormalidades , Epilepsia/genética , Polimorfismo de Nucleotídeo Único , Precursores de Proteínas/genética , Adolescente , Adulto , Alelos , Apoptose , Brasil/epidemiologia , Divisão Celular , Movimento Celular , Córtex Cerebral/patologia , Criança , Anormalidades Congênitas/epidemiologia , Anormalidades Congênitas/genética , Anormalidades Congênitas/patologia , Análise Mutacional de DNA , Epilepsia/epidemiologia , Epilepsia/patologia , Etnicidade/genética , Europa (Continente)/epidemiologia , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Proteínas Priônicas , PríonsRESUMO
BACKGROUND: Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) is the most common surgically remediable epileptic syndrome. Ablation of the cellular prion protein (PrP(c)) gene (PRNP) enhances neuronal excitability of the hippocampus in vitro and sensitivity to seizure in vivo, indicating that PrP(c) might be related to epilepsy. OBJECTIVE: To evaluate the genetic contribution of PRNP to MTLE-HS. METHODS: The PRNP coding sequence of DNA from peripheral blood cells of 100 consecutive patients with surgically treated MTLE-HS was compared to that from a group of healthy controls adjusted for sex, age, and ethnicity (n = 180). The presence of PRNP variant alleles was correlated with clinical and presurgical parameters as well as surgical outcome. RESULTS: A variant allele at position 171 (Asn-->Ser), absent in controls, was found in heterozygosis (Asn171Ser) in 23% of patients (p < 0.0001). The PRNP genotypes were not correlated with any clinical or presurgical data investigated. However, patients carrying the Asn171Ser variant had a five times higher chance of continuing to have seizures after temporal lobectomy (95% CI 1.65 to 17.33, p = 0.005) than those carrying the normal allele. At 18 months after surgery, 91.8% of patients with the normal allele at codon 171 were seizure free, in comparison to 68.2% of those carrying Asn171Ser (p = 0.005). CONCLUSIONS: The PRNP variant allele Asn171Ser is highly prevalent in patients with medically untreatable MTLE-HS and influences their surgical outcome. The results suggest that the PRNP variant allele at codon 171 (Asn171Ser) is associated with epileptogenesis in MTLE-HS.