RESUMO
Alphastatin, an endogenous angiogenesis inhibitor, has recently been used as an anticancer agent in several tumor models. This study was to investigate whether local sustained long-term expression of alphastatin could serve to diminish tumor growth of a human xenograft glioma model. We found that the recombinant alphastatin lentiviruses were able to stably infect HUVECs, and infected HUVECs could sustainably secrete alphastatin, which exhibited potent inhibitory effects on HUVECs migration, differentiation but not proliferation induced by vascular endothelial growth factor (VEGF) or basic fibroblast growth factor(bFGF). And the expression of secreted protein alphastatin markedly decreased tumor vascularization and inhibited tumor growth. Additionally, alphastatin inhibited VEGF- or bFGF-induced initial stage of angiogenesis by reducing JNk and ERK phosphorylation in vitro. Taken together, these data demonstrate that secreted protein alphastatin inhibits VEGF- or bFGF-induced angiogenesis by suppressing JNK and ERK kinases activation pathways in HUVECs, and markedly inhibits tumor angiogenesis in vivo. Consequently lentivirus-mediated gene transfer might represent an effective strategy for expression of alphastatin to achieve inhibition of human malignant glioma proliferation and tumor progression.
Assuntos
Fibrinogênio/genética , Terapia Genética/métodos , Glioma/terapia , Neovascularização Patológica/terapia , Animais , Western Blotting , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Células Endoteliais , Técnicas de Transferência de Genes , Vetores Genéticos , Glioma/patologia , Humanos , Imuno-Histoquímica , Lentivirus/genética , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Patológica/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Personal identification is an important work in forensic investigation included sex discrimination, age and stature estimation. Human identification depended on radiological image technique analysis is a practice and proper method in forensic science field. This paper intended to understand the advantage and defect by reviewed the employing of forensic radiology in forensic science field broadly and provide a reference to perfect the application of forensic radiology in forensic science field.
