Alcohol Increases Microglial Expression of Chemokine MIP-1 and MCP-1 mRNA

Fetal exposure to alcohol can lead to extensive pathology in the CNS causing fetal alcohol syndrome or alcohol-related neurodevelopmental disorder. Our previous research has revealed that alcohol has detrimental effects on development of neurons and glial cells, including microglia. However, the effects of alcohol on microglial function as well as interactions between microglia and neurons remain relatively unexplored. Microglia produce immunomodulatory cytokines and chemokines that directly control the survival, development, and function of neurons and glia. In this study, mouse N9 microglial cells were treated with 0.5% (w/v) ethanol for 12-48 hr with or without subsequent challenge with the cellular activator lipopolysaccharide. Microglial expression of the cytokines IL1,IL6,IL10,IL12, TNFcc, IFNy, and MIF, and the chemokines MCP-1, MIP-loc,MIP-1p, MIP-2, IP-10, TCA-3, and RANTES was quantified by ribonuclease protection assay of cellular RNA. The mRNA levels of MIP-1P, MlP-la, and MCP-1 RNA were increased 94% (

Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies