RESUMO
The aim of this study was to find related pathogenic genes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in (CADASIL)-like patients. The direct sequencing and high-throughput multiplex polymerase chain reaction (PCR) was performed to screen for related genes. The clinical and imaging data of a CADASIL-like patient (the pro-band) and his family members were collected. At first, the known hereditary cerebral vascular genes of the pro-band were screened with direct sequencing to find candidate gene mutations. High-throughput multiplex PCR was then used to analyze the single nucleotide polymorphism of the candidate gene in the family members. The results showed that there was missense mutation of the high temperature requirement protease A1 (HTRA1) gene in the pro-band, which may be a pathogenic factor according to the biological software analysis. The following SNP results revealed that the other family members also had the HTRA1 gene mutation. Thus, the CADASIL-like family disease may be caused by heterozygous HTRA1 gene mutation, which leads to autosomal dominant hereditary cerebral small vessel disease.
Assuntos
CADASIL/genética , Serina Peptidase 1 de Requerimento de Alta Temperatura A/genética , Mutação de Sentido Incorreto/genética , Adulto , Feminino , Predisposição Genética para Doença , Genótipo , Heterozigoto , Humanos , Masculino , Reação em Cadeia da Polimerase Multiplex , Linhagem , Polimorfismo de Nucleotídeo ÚnicoAssuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Glipicanas/antagonistas & inibidores , Neoplasias Hepáticas/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Antineoplásicos/química , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Citocinas/imunologia , Ensaios de Seleção de Medicamentos Antitumorais , Glipicanas/imunologia , Humanos , Ligantes , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Linfócitos T/imunologiaRESUMO
The aim of this study was to find related pathogenic genes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in (CADASIL)-like patients. The direct sequencing and high-throughput multiplex polymerase chain reaction (PCR) was performed to screen for related genes. The clinical and imaging data of a CADASIL-like patient (the pro-band) and his family members were collected. At first, the known hereditary cerebral vascular genes of the pro-band were screened with direct sequencing to find candidate gene mutations. High-throughput multiplex PCR was then used to analyze the single nucleotide polymorphism of the candidate gene in the family members. The results showed that there was missense mutation of the high temperature requirement protease A1 (HTRA1) gene in the pro-band, which may be a pathogenic factor according to the biological software analysis. The following SNP results revealed that the other family members also had the HTRA1 gene mutation. Thus, the CADASIL-like family disease may be caused by heterozygous HTRA1 gene mutation, which leads to autosomal dominant hereditary cerebral small vessel disease.
Assuntos
Humanos , Masculino , Feminino , Adulto , Mutação de Sentido Incorreto/genética , CADASIL/genética , Serina Peptidase 1 de Requerimento de Alta Temperatura A/genética , Linhagem , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase Multiplex , Genótipo , HeterozigotoRESUMO
Glioblastoma (GBM) is a highly angiogenic malignancy that is resistant to standard therapy; neo-formed vessels of this aggressive malignancy are thought to arise by sprouting of pre-existing brain capillaries. However, the conventional anti-angiogenic therapy, which seemed promising initially, shows transitory and incomplete efficacy. The discovery of vasculogenic mimicry (VM) has offered a new horizon for understanding tumor vascularization. VM is a tumor cell-constituted, matrix-embedded fluid-conducting meshwork that is independent of endothelial cells and is positively correlated with poor prognosis. Therefore, a better understanding of GBM vasculature is needed to optimize anti-angiogenic therapy. This review focuses on the signaling molecules and cascades involved in VM in relation to ongoing glioma research, as well as the clinical translational advances in GBM that have been offered by the development of optimized anti-angiogenesis treatment modalities.
RESUMO
Glioma is the most common malignancy of the central nervous system. Approximately 40 percent of intracranial tumors are diagnosed as gliomas. Difficulties in treatment are associated closely with the malignant phenotype, which is characterized by excessive proliferation, relentless invasion, and angiogenesis. Although the comprehensive treatment level of brain glioma is continuously progressing, the outcome of this malignancy has not been improved drastically. Therefore, the identification of new biomarkers for diagnosis and therapy of this malignancy is of significant scientific and clinical value. FRAT1 is a positive regulator of the Wnt/ß-catenin signaling pathway and is overexpressed in many human tumors. In the present study, we investigated the expression status of FRAT1 in 68 patients with human gliomas and its correlation with the pathologic grade, proliferation, invasion, angiogenesis, and prognostic significance. These findings suggest that FRAT1 may be an important factor in the tumorigenesis and progression of glioma and could be explored as a potential biomarker for pathological diagnosis, an indicator for prognosis, and a target for biological therapy of malignancy.