Integrated Genomic Analysis of Primary Prostate Tumor Foci and Corresponding Lymph Node Metastases Identifies Mutations and Pathways Associated with Metastasis.

Prostate cancer is a highly heterogeneous disease and mortality is mainly due to metastases but the initial steps of metastasis have not been well characterized. We have performed integrative whole exome sequencing and transcriptome analysis of primary prostate tumor foci and corresponding lymph node metastases (LNM) from 43 patients enrolled in clinical trial. We present evidence that, while there are some cases of clonally independent primary tumor foci, 87% of primary tumor foci and metastases are descended from a common ancestor.

Chimera RNA interference knockdown of γ-synuclein in human cortical astrocytes results in mitotic catastrophe.

Elevated levels of γ-synuclein (γ-syn) expression have been noted in the progression of glioblastomas, and also in the cerebrospinal fluid of patients diagnosed with neurodegenerative diseases. γ-Syn can be either internalized from the extracellular milieu or expressed endogenously by human cortical astrocytes. Internalized γ-syn results in increased cellular proliferation, brain derived neurotrophic factor release and astroprotection.

γ-Synuclein Induces Human Cortical Astrocyte Proliferation and Subsequent BDNF Expression and Release.

γ-Synuclein (γ-syn) is expressed by astrocytes in the human nervous system, and increased extracellularly in the brain and cerebrospinal fluid of individuals diagnosed with Alzheimer's disease. Upregulation of γ-syn also coincides with proliferation of glioblastomas and other cancers. In order to better understand regulation and function of extracellular γ-syn, primary human cortical astrocytes were treated with γ-syn conditioned media at various physiological concentrations (50, 100, 150 nM) after cell synchronization.