RESUMEN
Autoimmune diseases are chronic, life threatening, and of burgeoning public health concern. They rank among the 10 most common causes of death in women, and some have incidence rates surpassing those of heart disease and cancer. Emerging information regarding molecular and cellular mechanisms affords opportunities for the discovery of novel therapeutic strategies or the repurposing of FDA-approved pharmacologic agents. Yet, obstacles to drug development amplify as an inverse function of the incidence of rare autoimmune disease; challenges include heterogeneous clinical presentation, paucity of definitive biomarkers, and poorly validated measures of therapeutic response. An integrative continuum model to address these challenges is being applied to neuromyelitis optica (NMO)-a potentially devastating neurodegenerative process that has had limited therapeutic options. This model links target discovery with pharmacologic application to accelerate improved clinical efficacy. The application of such innovative strategies may help researchers overcome barriers to therapeutic advances in NMO and other rare autoimmune diseases.
Asunto(s)
Enfermedades Autoinmunes/tratamiento farmacológico , Neuromielitis Óptica/epidemiología , Enfermedades Raras/epidemiología , Animales , Enfermedades Autoinmunes/inmunología , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Femenino , Humanos , Neuromielitis Óptica/tratamiento farmacológico , Neuromielitis Óptica/inmunología , Salud Pública , Enfermedades Raras/tratamiento farmacológico , Enfermedades Raras/inmunología , Estados Unidos , United States Food and Drug AdministrationRESUMEN
A diagnosis of parathyroid hormone-related protein (PTH-rP)-secreting metastatic uterine epithelioid leiomyosarcoma was made in a 61-year-old woman with humoral hypercalcemia of malignancy. A primary uterine tumor had been removed 10 years previously, which had been associated with a short history of hypercalcemia. The original uterine tumor was diagnosed as a smooth muscle tumor of uncertain malignant potential. To the best of our knowledge, this is the first reported case of a PTH-rP-secreting uterine leiomyosarcoma. We demonstrate the dramatic changes in serum calcium, phosphorus, PTH, and PTH-rP levels after tumor resection. Extensive biochemical analysis and detailed immunohistochemical and ultrastructural characterization demonstrate several features of this tumor.