RESUMEN
INTRODUCTION: Golimumab is a human anti-TNF monoclonal antibody that was derived from human antibody-transgenic mice. Golimumab demonstrated meaningful clinical benefit and tolerable safety in patients with active rheumatoid arthritis (RA) who were methotrexate (MTX)-naïve, or who inadequately responded to MTX or who had previously been treated with a TNF inhibitor. AREAS COVERED: This review summarizes published data on the clinical efficacy and safety for golimumab (including its pharmacodynamic and pharmacokinetic characteristics) from multiple global phase III and Japanese phase II/III clinical trials. In the long term extension of three Phase III studies with subcutaneous golimumab, the reported retention rate is high. EXPERT OPINION: Golimumab binds TNF with high affinity and can be delivered subcutaneously every 4 weeks. Like other IgG1 antibodies, FcγR functions suggests that antibody dependent cellular cytotoxicity is observed but the contribution of cell lysis to efficacy is unclear. Although anti-TNFα agents made it possible to achieve clinical remission in RA patients, there is still an unmet need to develop treatments that will enable them to discontinue all RA medication and maintain drug-free remission.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Antirreumáticos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Animales , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacología , Antirreumáticos/efectos adversos , Antirreumáticos/farmacología , Ensayos Clínicos Fase III como Asunto , Humanos , Metotrexato/uso terapéutico , Ratones , Ratones Transgénicos , Inducción de Remisión/métodos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresAsunto(s)
Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/inmunología , Animales , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/farmacocinética , Artritis Psoriásica/tratamiento farmacológico , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Semivida , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Ratones , Receptores Fc/fisiologíaAsunto(s)
Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Transcriptasa Inversa del VIH/farmacología , Transcriptasa Inversa del VIH/uso terapéutico , Piridazinas/farmacología , Piridazinas/uso terapéutico , Replicación Viral/efectos de los fármacos , Fármacos Anti-VIH/química , Ensayos Clínicos Fase III como Asunto , Depresión Química , Farmacorresistencia Viral , Quimioterapia Combinada , Transcriptasa Inversa del VIH/química , VIH-1/efectos de los fármacos , VIH-1/fisiología , Humanos , Nitrilos , Piridazinas/química , Pirimidinas , Ensayos Clínicos Controlados Aleatorios como AsuntoAsunto(s)
Antineoplásicos/farmacología , Ácidos Borónicos/farmacología , Ácidos Borónicos/uso terapéutico , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/uso terapéutico , Pirazinas/farmacología , Pirazinas/uso terapéutico , Animales , Antineoplásicos/uso terapéutico , Bortezomib , HumanosRESUMEN
Proteolytic enzyme-mediated degradation of the extracellular matrix (ECM) is crucial for the formation of both tumor metastasis and angiogenesis. Recently, several reports have suggested that aminopeptidases are involved in this process, but precisely how is largely unknown. We found here that aminopeptidase N (APN/CD13) was selectively expressed in vascular endothelial cells including human umbilical vein endothelial cells (HUVEC) and human aortic endothelial cells (HAEC), and was not detectable in a majority of normal cells and tumor cell lines we examined. RNA interference (RNAi) of APN resulted in the inhibition of capillary tube formation of HUVEC on Matrigel. APN siRNA suppressed the migration of HUVEC through a fibronectin-coated Transwell membrane, and reduced the cellular adhesion to Matrigel and various adhesion molecules including type IV collagen, type I collagen and fibronectin. These findings suggest that APN is a multifunctional protein with important roles in vascular endothelial morphogenesis during angiogenesis.