Systemic Therapy for Melanoma Brain and Leptomeningeal Metastases.

Melanoma has a high propensity to metastasize to the brain which portends a poorer prognosis. With advanced radiation techniques and targeted therapies, outcomes however are improving. Melanoma brain metastases are best managed in a multi-disciplinary approach, including medical oncologists, neuro-oncologists, radiation oncologists, and neurosurgeons.

Neutral ceramidase secreted by endothelial cells is released in part associated with caveolin-1.

Neutral ceramidase (CDase) is a key enzyme of sphingomyelin (SM) metabolism implicated in cell signaling triggered by a variety of extracellular ligands. Previously it was shown that in murine endothelial cells a portion of neutral CDase is localized in detergent-resistant light membranes. In this study subcellular distribution of neutral CDase was further investigated.

Localization of neutral ceramidase in caveolin-enriched light membranes of murine endothelial cells.

Sphingomyelinase (SMase) and ceramidase (CDase) activities participate in sphingomyelin (SM) metabolism and have a role in the signal transduction of a variety of ligands. In this study evidence is presented that caveolin-enriched light membranes (CELMs) of murine endothelial cells, characterized by high SM, ceramide (Cer) and cholesterol content, bear acid and neutral SMase as well as neutral CDase activities. Localization of neutral CDase in CELMs was confirmed by Western analysis.

Permissive role of protein kinase C alpha but not protein kinase C delta in sphingosine 1-phosphate-induced Rho A activation in C2C12 myoblasts.

Rho GTPases participate in various important signaling pathways and have been implicated in myogenic differentiation. Here the first evidence is provided that in C2C12 myoblasts sphingosine 1-phosphate (SPP) rapidly and transiently induced membrane association of Rho A in a pertussis toxin-insensitive manner. The bioactive lipid preferentially relocalized the GTPase to Golgi-enriched membrane.

Neutral/alkaline and acid ceramidase activities are actively released by murine endothelial cells.

Ceramidases (CDase(s)) play a key role in sphingolipid metabolism by hydrolyzing ceramide into sphingosine. Here we report that murine endothelial cells, macrophages, and human fibroblasts are all able to release acid as well as neutral/alkaline CDase activities in the culture medium. Endothelial cells were characterized by the highest specific activity of cellular as well as secreted CDases.