Osteosarcomas are bone tumors that frequently metastasize to the lung. Aberrant expression of the transcription factor, runt‐related transcription factor 2 (RUNX2), is a key pathological feature in osteosarcoma and associated with loss of p53 and miR‐34 expression. Elevated RUNX2 may transcriptionally activate genes mediating tumor progression and metastasis, including the RUNX2 target gene osteopontin (OPN/SPP1). This gene encodes a secreted matricellular protein produced by osteoblasts to regulate bone matrix remodeling and tissue calcification. Here we investigated whether and how the RUNX2/OPN axis regulates lung metastasis of osteosarcoma. Importantly, RUNX2 depletion attenuates lung metastasis of osteosarcoma cells in vivo. Using next‐generation RNA‐sequencing, protein‐based assays, as well as the loss‐ and gain‐of‐function approaches in selected osteosarcoma cell lines, we show that osteopontin messenger RNA levels closely correlate with RUNX2 expression and that RUNX2 controls the levels of secreted osteopontin. Elevated osteopontin levels promote heterotypic cell–cell adhesion of osteosarcoma cells to human pulmonary microvascular endothelial cells, but not in the presence of neutralizing antibodies. Collectively, these findings indicate that the RUNX2/OPN axis regulates the ability of osteosarcoma cells to attach to pulmonary endothelial cells as a key step in metastasis of osteosarcoma cells to the lung.

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Prognosis for patients with Wilms tumor treated on TWPINDA-99 seems to be better than previous national trials and is similar to developed countries.

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Hypercalcemia is an infrecuent complication in pediatric oncology, with an incidence between 0,5 and 3%. It can occur at diagnosis, during the disease course or at relapse, and it is resolved by treating the underlying pathology, requiring in some cases the use of specifi c therapy such as calcitonin and biphosphonates. This article presents 3 cases of children with cancer and hypercalcemia during their illness, analyzing its clinical presentation, pathophysiology and treatment. (Key words: Tumoral hypercalcemia, pediatric oncology, paraneoplasic syndrome). Rev Chil Pediatr 2010; 81 (4): 347-352 RESUMENLa hipercalcemia es una complicación infrecuente en niños con cáncer, con una incidencia que oscila entre 0,5 y 3%. Se puede presentar al diagnóstico, durante el tratamiento o en la recaída de una neoplasia, se resuelve al tratar la enfermedad de base, pudiendo además, requerir el uso de terapia específi ca como calcitonina y bifosfonatos. En el presente artículo se revisan 3 casos clínicos de niños con cáncer que presentaron hipercalcemia en algún momento de su enfermedad, se discute su forma de presentación, fi siopatología y manejo. (Palabras clave: Hipercalcemia Tumoral, cáncer Infantil, Síndrome paraneoplásico). Rev Chil Pediatr 2010; 81 (4): 347-352 CASO CLÍNICO CLINICAL CASE Rev Chil Pediatr 2010; 81 (4): 347-352Trabajo recibido el 13 de noviembre de 2009, devuelto para corregir el 28 de diciembre de 2009, segunda versión el 24 de mayo de 2010, aceptado para publicación el 01 de junio de 2010.