MicroRNAs (miRNAs) are short, non-coding RNAs that target and silence protein coding genes through 3-UTR elements. Evidence increasingly assigns an immunosuppressive role for miRNAs in immunity, but relatively few miRNAs have been studied, and an overall understanding of the importance of these regulatory transcripts in complex in vivo systems is lacking.Here we have applied multiple technologies to globally analyze miRNA expression and function in allergic lung disease, an experimental model of asthma. Deep sequencing and microarray analyses of the mouse lung short RNAome revealed numerous extant and novel miRNAs and other transcript classes. Similar to mRNAs, lung miRNA expression changed dynamically during the transition from the naive to the allergic state, suggesting numerous functional relationships. A possible role for miRNA editing in altering the lung mRNA target repertoire was also identified. Multiple members of the highly conserved let-7 miRNA family were the most abundant lung miRNAs, and we confirmed in vitro that interleukin 13 (IL-13), a cytokine essential for expression for allergic lung disease, is regulated by mmulet-7a. However, inhibition of let-7 miRNAs in vivo using a locked nucleic acid profoundly inhibited production of allergic cytokines and the disease phenotype. Our findings thus reveal unexpected complexity in the miRNAome underlying allergic lung disease and demonstrate a proinflammatory role for let-7 miRNAs. MicroRNAs (miRNAs)3 are short regulatory RNAs with the potential to target and suppress multiple genes across diverse signaling pathways comprising biologically meaningful networks. Consequently, miRNAs that are inappropriately expressed in the context of specific diseases are of particular interest as therapeutic targets if they can be shown to coordinate such networks. Initially transcribed as relatively long primary transcripts, pri-miRNAs are subsequently modified by the nuclear RNAses Drosha and Pasha to yield precursor miRNAs (pre-miRNAs) that are further processed by the cytoplasmic RNase III Dicer to form short double-stranded miR-miR* duplexes, one strand of which (miR) is then integrated into the RNA-induced silencing complex that includes the enzymes Dicer and Argonaute (Ago). The mature miRNAs (ϳ17-24 nt) direct the RNA-induced silencing complex to specific target sites located within the 3Ј-UTR of target genes. Once bound to target sites, miRNAs repress translation through mRNA decay, translational inhibition, and/or sequestration into processing bodies (1-3).Recent estimates indicate that over 60% of protein-coding genes carry 3Ј-UTR miRNA target sites, suggesting a role for miRNAs in the control of gene expression in diverse processes (4). Indeed, miRNAs have now been firmly linked to the regulation of early development (5), cell proliferation, and cell death (6); apoptosis and fat metabolism (7); and cell differentiation (8). In addition, studies of miRNA expression in chronic lymphocytic leukemia (9), colonic adenocarcinoma (10), Burkitt lymphoma, and cardiac ...

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In our institutional analysis of patients treated with SRS and various systemic immunologic and targeted melanoma agents, significant differences in distant MBM control and OS are noted. Prospective evaluation of the potential synergistic effect between these agents and SRS is warranted.

RT for MCC was associated with improved LRC and survival. RT appeared to be beneficial regardless of margin status.

Patients with Medicaid insurance more often present with locally advanced HNC and experience a higher rate of treatment delays compared with non-Medicaid patients. Medicaid insurance status appears to be independently associated with deficits in LRC and OS. Improvements in the health care system, such as expediting treatment initiation, may improve the outcomes of patients with HNC. Cancer 2016;122:3529-3537. © 2016 American Cancer Society.