Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros












Base de datos
Intervalo de año de publicación
1.
Endocrinology ; 146(8): 3235-43, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15845617

RESUMEN

Humoral hypercalcemia of malignancy (HHM) is mediated primarily by skeletal and renal responses to tumor-derived PTHrP. PTHrP mobilizes calcium from bone by inducing the expression of receptor activator for nuclear factor-kappaB ligand (RANKL), a protein that is essential for osteoclast formation, activation, and survival. RANKL does not influence renal calcium reabsorption, so RANKL inhibition is a rational approach to selectively block, and thereby reveal, the relative contribution of bone calcium to HHM. We used the RANKL inhibitor osteoprotegerin (OPG) to evaluate the role of osteoclast-mediated hypercalcemia in two murine models of HHM. Hypercalcemia was induced either by sc inoculation of syngeneic colon (C-26) adenocarcinoma cells or by sc injection of high-dose recombinant PTHrP (0.5 mg/kg, s.c., twice per day). In both models, OPG (0.2-5 mg/kg) caused rapid reversal of established hypercalcemia, and the speed and duration of hypercalcemia suppression were significantly greater with OPG (5 mg/kg) than with high-dose bisphosphonates (pamidronate or zoledronic acid, 5 mg/kg). OPG also caused greater reductions in osteoclast surface and biochemical markers of bone resorption compared with either bisphosphonate. In both models, hypercalcemia gradually returned despite clear evidence of ongoing suppression of bone resorption by OPG. These data demonstrate that osteoclasts and RANKL are important mediators of HHM, particularly in the early stages of the condition. Aggressive antiresorptive therapy with a RANKL inhibitor therefore might be a rational approach to controlling HHM.


Asunto(s)
Adenocarcinoma/prevención & control , Resorción Ósea/prevención & control , Proteínas Portadoras/antagonistas & inhibidores , Neoplasias del Colon/prevención & control , Difosfonatos/farmacología , Glicoproteínas/farmacología , Hipercalcemia/prevención & control , Glicoproteínas de Membrana/antagonistas & inhibidores , Adenocarcinoma/sangre , Animales , Antineoplásicos/farmacología , Calcio/sangre , Línea Celular Tumoral , Neoplasias del Colon/sangre , Modelos Animales de Enfermedad , Humanos , Hipercalcemia/etiología , Ligandos , Ratones , FN-kappa B/metabolismo , Osteoprotegerina , Pamidronato , Proteína Relacionada con la Hormona Paratiroidea/fisiología , Ligando RANK , Receptor Activador del Factor Nuclear kappa-B , Receptores Citoplasmáticos y Nucleares , Receptores del Factor de Necrosis Tumoral
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...