RESUMEN
Many antitumor drugs have a limited ability to penetrate more than a few cell diameters from blood vessels into solid tumors, which limits their effectiveness. In this study, we investigated whether the biological activity of endostatin can be enhanced by the addition of an integrin-targeting and permeability-enhancing sequence. The internalization RGD (CRGDKGPDC; iRGD) sequence was added at the carboxyl terminus of endostatin. Modification of endostatin with the iRGD motif showed specific and increased binding to endothelial cells; the increased binding correlated with an improved antiangiogenic property. iRGD-modified endostatin was more effective than human endostatin in inhibiting liver cancer growth in athymic mice. The finding indicates that addition of a vascular targeting and permeability sequence can enhance the biological activity of an antiangiogenic molecule and tumor targeting.
Asunto(s)
Endostatinas/administración & dosificación , Endostatinas/farmacocinética , Oligopéptidos/administración & dosificación , Oligopéptidos/farmacocinética , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/farmacocinética , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Secuencia de Bases , Permeabilidad Capilar , Bovinos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Péptidos de Penetración Celular/administración & dosificación , Péptidos de Penetración Celular/genética , Péptidos de Penetración Celular/farmacocinética , Embrión de Pollo , Endostatinas/genética , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Endotelio Vascular/citología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Femenino , Humanos , Integrinas/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Ratones , Ratones Desnudos , Datos de Secuencia Molecular , Oligopéptidos/genética , Unión Proteica , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/farmacocinéticaRESUMEN
Nitrobenzene is one of the toxic compounds. Much work had focused on biodegradation of it sofar. Two main pathways for nitrobenzene biodegradation, oxidative and partial reductive pathways, were reviewed in this article. The mechanism of these pathways including involved enzymes and genes was introduce in details. Comparative analysis of the pathways would provide basis for the development and application of biodegradation technology for nitrobenzene and other organic pollutants.