RESUMO
BACKGROUND: Gliomas is a major challenge of current medical system, and thousands of people are struggling in the pain of this disease worldwide. In the last decade, the functions of miRNAs have been revealed by many studies, and the intervention on miRNA dysfunctions has been thought as a promising way to counter cancer. MiR-493-5p has been identified as a tumor inhibitor to suppress the progressions of several tumors while its role in gliomas remains unknown. Hence, the study investigated the expression levels of miR-493-5p in glioma tissues and cell lines. METHODS: CCK-8 assay, transwell assay and flow cytometry assay were used to observe the effects of miR-493-5p on tumor cells. The downstream targets of miR-493-5p were also searched and verified with online databases and dual-luciferase reporter assay. Moreover, the activities of P53 and PI3K/AKT pathways were also explored by western blot to illustrate the regulation mechanism of miR-493-5p on glioma development. RESULTS: The results showed that miR-493-5p was significantly downregulated in pathological tissues and glioma cell lines, and the increased miR-493-5p effectively inhibited the malignant behavior and promoted the apoptosis of glioma cells. CONCLUSIONS: E2F3 was confirmed as a target of miR-493-5p, and the effects of miR-493-5p on the phenotype of glioma cells could be partly reversed by E2F3. Besides, it was also found that miR-493-5p could effectively suppress the expression of E2F3 and then improve the dysfunctions of the P53 and PI3K/AKT pathways.
Assuntos
Neoplasias Encefálicas/etiologia , Fator de Transcrição E2F3/fisiologia , Glioma/etiologia , MicroRNAs/fisiologia , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Proteína Supressora de Tumor p53/fisiologia , Linhagem Celular Tumoral , Humanos , Transdução de SinaisRESUMO
The molecular biology of human glioma is a complex and fast-growing field in which basic research needs to meet clinical expectations in terms of anti-tumor efficacy. Although much effort is being done in molecular biology research, significant contribution to the quality of life and overall survival still lacks. The vastness of molecular biology literature makes it virtually impossible for clinicians to keep up to date in the field. This paper reviews some practical concepts regarding glioma tumorigenesis from the clinician's perspective. Five main aspects are discussed: major intracellular signaling pathways involved in glioma formation; genomic, epigenetic and transcriptomic relevant features of glioma; the prognostic and predictive values of molecular markers according to the new WHO classification of glial tumors; the importance of molecular and cellular heterogeneity in glioblastoma, responsible for its therapy resistance; and the interaction between glioma and the immune system, in view of the novel and promising targeted therapies.
Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/etiologia , Neoplasias Encefálicas/patologia , Glioma/irrigação sanguínea , Glioma/etiologia , Glioma/patologia , Humanos , Biologia Molecular , Transdução de Sinais/fisiologia , TranscriptomaRESUMO
Gliomas are the most common type of primary brain tumors. The most aggressive type, Glioblastoma multiforme (GBM), is one of the deadliest human diseases, with an average survival at diagnosis of about 1 year. Previous evidence suggests a link between human cytomegalovirus (HCMV) and gliomas. HCMV has been shown to be present in these tumors and several viral proteins can have oncogenic properties in glioma cells. Here we have investigated the presence of HCMV DNA, RNA and proteins in fifty-two gliomas of different grades of malignancy. The UL83 viral region, the early beta 2.7 RNA and viral protein were detected in 73%, 36% and 57% by qPCR, ISH and IHC, respectively. Positivity of the viral targets and viral load was independent of tumor type or grade suggesting no correlation between viral presence and tumor progression. Our results demonstrate high prevalence of the virus in gliomas from Brazilian patients, contributing to a better understanding of the association between HCMV infection and gliomas worldwide and supporting further investigations of the virus oncomodulatory properties.
Assuntos
Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/virologia , Citomegalovirus/genética , DNA Viral , Expressão Gênica , Glioma/etiologia , Glioma/patologia , Carga Viral , Brasil , Humanos , Imuno-Histoquímica , Hibridização In Situ , Gradação de Tumores , RNA Viral , Proteínas Virais/genética , Proteínas Virais/metabolismoRESUMO
Neurofibromatosis type 1 (NF1) is a genetic disorder that predisposes patients to the formation of sporadic tumors and also increases the risk of radiation-induced malignancies. The most commonly described radiation-induced tumor in NF1 patients is a malignant peripheral nerve sheath tumor. We present 2 children with NF1 who received radiation therapy and subsequently developed high-grade gliomas. We then review the current literature on radiation-induced tumors in NF1 patients. Although radiation may be the most appropriate therapy in specific situations for children with NF1, the secondary tumor risk should be carefully considered.
Assuntos
Neoplasias Encefálicas/etiologia , Glioma/etiologia , Neoplasias Induzidas por Radiação/patologia , Neurofibromatose 1/radioterapia , Criança , Pré-Escolar , Humanos , Neurofibromatose 1/patologiaRESUMO
Epidermal growth factor (EGF) plays an important role in cancer. A functional single nucleotide polymorphism (SNP) in the 5'-untranslated region of the EGF gene (+61 A>G) may influence its expression and contribute to cancer predisposition and aggressiveness. Aiming to investigate the role of EGF +61 A>G in the susceptibility to glioma and its prognosis, we performed a case-control study with 165 patients and 200 healthy controls from Brazil. Comparisons of genotype distributions and allele frequencies did not reveal any significant differences between the groups. The mean overall survival was 9.2 months for A/A, 8.2 months for A/G, and 7.7 months for G/G. When survival curves were plotted we found that the +61G allele is associated with poor overall survival (p=0.023) but not with disease-free survival (p=0.527). Our data suggest that, although there is no association between the EGF +61 A>G genotype and glioma susceptibility, this SNP is associated with shorter overall survival of glioma patients in the Brazilian population. Nevertheless, future studies utilizing a larger series are essential for a definitive conclusion.
Assuntos
Fator de Crescimento Epidérmico/genética , Glioma/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Fator de Crescimento Epidérmico/fisiologia , Feminino , Genótipo , Glioma/etiologia , Glioma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de RiscoRESUMO
The TP53 tumor suppressor gene codifies a protein responsible for preventing cells with genetic damage from growing and dividing by blocking cell growth or apoptosis pathways. A common single nucleotide polymorphism (SNP) in TP53 codon 72 (Arg72Pro) induces a 15-fold decrease of apoptosis-inducing ability and has been associated with susceptibility to human cancers. Recently, another TP53 SNP at codon 47 (Pro47Ser) was reported to have a low apoptosis-inducing ability; however, there are no association studies between this SNP and cancer. Aiming to study the role of TP53 Pro47Ser and Arg72Pro on glioma susceptibility and oncologic prognosis of patients, we investigated the genotype distribution of these SNPs in 94 gliomas (81 astrocytomas, 8 ependymomas and 5 oligodendrogliomas) and in 100 healthy subjects by the polymerase chain reaction-restriction fragment length polymorphism approach. Chi-square and Fisher exact test comparisons for genotype distributions and allele frequencies did not reveal any significant difference between patients and control groups. Overall and disease-free survivals were calculated by the Kaplan-Meier method, and the log-rank test was used for comparisons, but no significant statistical difference was observed between the two groups. Our data suggest that TP53 Pro47Ser and Arg72Pro SNPs are not involved either in susceptibility to developing gliomas or in patient survival, at least in the Brazilian population.
Assuntos
Glioma/genética , Polimorfismo de Nucleotídeo Único , Proteína Supressora de Tumor p53/genética , Adolescente , Adulto , Idoso , Apoptose/genética , Brasil , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Frequência do Gene , Genes p53 , Predisposição Genética para Doença , Genótipo , Glioma/etiologia , Glioma/mortalidade , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de SobrevidaRESUMO
The TP53 tumor suppressor gene codifies a protein responsible for preventing cells with genetic damage from growing and dividing by blocking cell growth or apoptosis pathways. A common single nucleotide polymorphism (SNP) in TP53 codon 72 (Arg72Pro) induces a 15-fold decrease of apoptosis-inducing ability and has been associated with susceptibility to human cancers. Recently, another TP53 SNP at codon 47 (Pro47Ser) was reported to have a low apoptosis-inducing ability; however, there are no association studies between this SNP and cancer. Aiming to study the role of TP53 Pro47Ser and Arg72Pro on glioma susceptibility and oncologic prognosis of patients, we investigated the genotype distribution of these SNPs in 94 gliomas (81 astrocytomas, 8 ependymomas and 5 oligodendrogliomas) and in 100 healthy subjects by the polymerase chain reaction-restriction fragment length polymorphism approach. Chi-square and Fisher exact test comparisons for genotype distributions and allele frequencies did not reveal any significant difference between patients and control groups. Overall and disease-free survivals were calculated by the Kaplan-Meier method, and the log-rank test was used for comparisons, but no significant statistical difference was observed between the two groups. Our data suggest that TP53 Pro47Ser and Arg72Pro SNPs are not involved either in susceptibility to developing gliomas or in patient survival, at least in the Brazilian population.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Glioma/genética , Polimorfismo de Nucleotídeo Único , /genética , Apoptose/genética , Brasil , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Glioma/etiologia , Glioma/mortalidade , Prognóstico , Análise de SobrevidaRESUMO
Recent studies suggest that neurocysticercosis may be a risk factor for human cancer. Pathogenetic mechanisms explaining possible oncogenic effects of cysticerci include the following: (a) parasite-induced modulation of the host immune response that may be associated with loss of regulatory mechanisms implicated in the immunological surveillance against cancer; (b) transfer of genetic material from the parasite to the host, causing DNA damage and malignant transformation of host cells, and (c) chronic inflammation with liberation of nitric oxide and inhibition of tumor suppressor genes. Further research is needed to confirm the potential role of cysticercosis in the development of cancer. These studies should determine the presence of cysticercotic factors responsible for the transfer of genetic material and potential mutations in the tumor suppressor genes in proliferating astrocytes surrounding cysticercotic lesions. Additionally, the complex interaction between the immune state of the host with variable cytokine release and the presence of inflammatory cells releasing nitric oxide that cause DNA damage and impair tumor suppressive mechanisms needs to be investigated.
Assuntos
Neoplasias/etiologia , Neurocisticercose/complicações , Animais , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/etiologia , Transformação Celular Neoplásica , Comorbidade , Cysticercus/genética , Cysticercus/imunologia , Cysticercus/patogenicidade , Suscetibilidade a Doenças , Genes de Helmintos , Glioma/epidemiologia , Glioma/etiologia , Interações Hospedeiro-Parasita , Humanos , Hospedeiro Imunocomprometido , Inflamação , Neoplasias/epidemiologia , Neoplasias/imunologia , Neurocisticercose/epidemiologia , Fatores de RiscoRESUMO
Se estudiaron durante tres años (1997-1999) los trihalometanos (subproductos de la cloración del agua) en dos plantas potabilizadoras del sudeste de Córdoba, Argentina que utilizan hipoclorito como desinfectante. Se analizó la cantidad y los tipos de trihalometanos (THMs) presentes en el agua. De acuerdo a los resultados de las aguas, el THM que predomina es el cloroformo siendo la media para la ciudad de Bell Ville de 102,6 ug/l y 100,3 ug/l para la localidad de San Marcos. Estos datos sugieren la utilización de metodologías alternativas para minimizar la cantidad de cloro a consumir por los humanos (AU)
Assuntos
Humanos , Trialometanos , Poluição Química da Água/análise , Água Potável , Carcinógenos/efeitos adversos , Argentina , Mutagênicos , Valores de Referência , Poluentes Químicos , Neoplasias da Bexiga Urinária/etiologia , Neoplasias Colorretais/etiologia , Neoplasias Renais/etiologia , Linfoma/etiologia , Neoplasias Pancreáticas/etiologia , Glioma/etiologia , Purificação da Água , Microbiologia da Água , Desinfecção da Água , Poluentes da Água/análise , Poluentes da Água/efeitos adversos , Estações de Tratamento , Exposição a Produtos QuímicosRESUMO
Se revisan los principales marcadores cutáneos congénitos de patología del sistema nervioso central, tanto los de disrafias del tubo neural, como los marcadores cutáneos no asociados a este fenómeno. Es importante tener un alto índice de sospecha al evaluar neonatos y lactantes, dado que un diagnóstico precoz puede modificar el pronóstico neurológico, mejorando la calidad de vida de estos pacientes
Assuntos
Humanos , Recém-Nascido , Anormalidades da Pele/etiologia , Disrafismo Espinal/diagnóstico , Cisto Dermoide/etiologia , Displasia Ectodérmica/etiologia , Glioma/etiologia , Hemangioma/etiologia , Hipertricose/etiologia , Meningomielocele/etiologia , Nevo Pigmentado/etiologia , Síndrome de Bandas Amnióticas/etiologia , Telangiectasia/etiologiaRESUMO
Se presenta el caso de una paciente de 3 años y 10 meses cuya sintomatología neurológica, de 3 meses de evolución, consistía en rotación externa de pie izquierdo y arrastre del pie en marcha, asociado a cambios de comportamiento. En los estudios imagenologicos con escanografía y resonancia magnética, se evidenció una gran masa en lóbulo temporal derecho heterogénea, de bordes bien delimitados. WEs llevada a cirugía y el gran reporte histológico e inmunohistoquímico GFAP (Proteína Acida Glial Fibrilar) es de Xantoastrocitoma pleomorfico, como hallazgo adicional se encontró actividad mitótica aumentada lo cual habla de mal pronostico
Assuntos
Humanos , Astrocitoma/complicações , Astrocitoma/diagnóstico , Astrocitoma/cirurgia , Glioma/diagnóstico , Glioma/etiologia , Glioma/fisiopatologiaRESUMO
Os autores relatam o caso de uma paciente de 19 anos de idade, com quadro característico de esclerose tuberosa, que evoluiu com hemorragia maciça em astrocitoma subependimário de células gigantes e óbito súbito. Aspectos da fisiopatologia do sangramento säo discutidos
Assuntos
Adulto , Humanos , Feminino , Hemorragia Cerebral/fisiopatologia , Glioma/etiologia , Esclerose Tuberosa/complicaçõesAssuntos
Humanos , Adolescente , Criança , Adulto , Astrocitoma , Astrocitoma/congênito , Astrocitoma/diagnóstico , Astrocitoma/patologia , Neoplasias , Neoplasias/classificação , Neoplasias/congênito , Neoplasias/diagnóstico , Neoplasias/etiologia , Neoplasias/metabolismo , Neoplasias/patologia , Glioma , Glioma/complicações , Glioma/congênito , Glioma/diagnóstico , Glioma/etiologia , Glioma/patologia , Glioma/radioterapia , Hemangioblastoma , Hemangioblastoma/congênito , Hemangioblastoma/diagnóstico , Hemangioblastoma/etiologia , Hemangioblastoma/patologia , Meduloblastoma , Meduloblastoma/congênito , Meduloblastoma/diagnóstico , Meduloblastoma/etiologia , Meduloblastoma/patologia , Neuroma Acústico/complicações , Neuroma Acústico/congênito , Neuroma Acústico/diagnóstico , Neuroma Acústico/etiologia , Neuroma Acústico/patologia , Neuroma Acústico/prevenção & controleRESUMO
Se expone la importancia del conocimiento de los aspectos clínicos y genéticos de los diferentes transtornos Neurocutáneos. Presentamos la serie personal del Profesor I. Pascual Castroviejo, de pacientes en el Servicio de Neurología Infantil a lo largo de 23.5 años. Esta serie está constituida por 174 casos de NEUROFIBROMATOSIS, 139 casos de Esclerosis Tuberosa, 48 casos de Incontinencia Pigmentaria Acromiante de Ito, 41 casos de síndrome de Stuger-Weber, 14 casos de Nevus Sebaceous de Jadassohn, 8 casos de Cutis Marmorata Telangiectásica congénita, 8 casos de Angioma Capilar, 8 casos de Melanosis Neurocutánea, 6 casos de síndrome de Sjogren-Larsson, 4 casos de Neuvus Fuscuceruleous de Ota, 3 casos de Incontinencia Pigmenti, 2 casos de síndrome de Goltz y 1 caso de Displasia Cerebelotrigeminal. Exponemos un seguimiento de 15 casos de NEUROFIBROMATOSIS TIPO - I entre Enero y Julio de 1990.
Assuntos
Humanos , Masculino , Feminino , Neurofibromatoses/complicações , Glioma/etiologia , Astrocitoma/etiologia , Aqueduto do Mesencéfalo/lesões , Meduloblastoma/etiologiaRESUMO
Se presentan 31 casos de quistes intracraneanos no parasitarios discriminados asi: quistes porencefálicos congénitos: 8 casos; quistes porencefálicos adquiridos (post-traumáticos, post-infeccioso, post-quirúrgico, post-accidente cerebrovascular): 6 casos; quistes aracnoideos de la fosa posterior; 3 casos; quistes aracnoideos supratentoriales; 1 caso; quistes tumorales de la fosa posterior: 3 casos; quistes tumorales supratentoriales: 3 casos; tubicamientos ventriculares: 6 casos; suprasellar: 1 caso. Se describen las diferentes técnicas utilizadas en el tratamiento de los mismos según la etiología