Extracellular vesicles as an emerging tool for the early detection of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by a series of interacting pathophysiological cascades, including the aggregation of β-amyloid plaques and the formation of neurofibrillary tangles derived from hyperphosphorylated tau proteins. AD is the cause of approximately 70 % of dementia, an irreversible and untreatable syndrome at its late stage. Hence, more efforts should be devoted to identifying at-risk or preclinical AD populations for early intervention and the improved design of drug trials.

The transcription cofactor c-JUN mediates phenotype switching and BRAF inhibitor resistance in melanoma.

Most patients with BRAF-mutant metastatic melanoma display remarkable but incomplete and short-lived responses to inhibitors of the BRAF kinase or the mitogen-activated protein kinase kinase (MEK), collectively BRAF/MEK inhibitors. We found that inherent resistance to these agents in BRAF(V600)-mutant melanoma cell lines was associated with high abundance of c-JUN and characteristics of a mesenchymal-like phenotype. Early drug adaptation in drug-sensitive cell lines grown in culture or as xenografts, and in patient samples during therapy, was consistently characterized by down-regulation of SPROUTY4 (a negative feedback regulator of receptor tyrosine kinases and the BRAF-MEK signaling pathway), increased expression of JUN and reduced expression of LEF1.

Phenotype switching in melanoma: implications for progression and therapy.

Epithelial-mesenchymal transition (EMT) is a key process associated with the progression of epithelial cancers to metastatic disease. In melanoma, a similar process of phenotype switching has been reported and EMT-related genes have been implicated in promotion to a metastatic state. This review examines recent research on the role of signaling pathways and transcription factors regulating EMT-like processes in melanoma and their association with response to therapy in patients, especially response to BRAF inhibition, which is initially effective but limited by development of resistance and subsequent progression.