Phototherapy Restores Deficient Type I IFN Production and Enhances Antitumor Responses in Mycosis Fungoides.

Transcriptional profiling demonstrated markedly reduced type I IFN gene expression in untreated mycosis fungoides (MF) skin lesions compared with that in healthy skin. Type I IFN expression in MF correlated with antigen-presenting cell-associated IRF5 before psoralen plus UVA therapy and epithelial ULBP2 after therapy, suggesting an enhancement of epithelial type I IFN. Immunostains confirmed reduced baseline type I IFN production in MF and increased levels after psoralen plus UVA treatment in responding patients. Effective tumor clearance was associated with increased type I IFN expression, enhanced recruitment of CD8+ T cells into skin lesions, and expression of genes associated with antigen-specific T-cell activation. IFNk, a keratinocyte-derived inducer of type I IFNs, was increased by psoralen plus UVA therapy and expression correlated with upregulation of other type I IFNs. In vitro, deletion of keratinocyte IFNk decreased baseline and UVA-induced expression of type I IFN and IFN response genes. In summary, we find a baseline deficit in type I IFN production in MF that is restored by psoralen plus UVA therapy and correlates with enhanced antitumor responses. This may explain why MF generally develops in sun-protected skin and suggests that drugs that increase epithelial type I IFNs, including topical MEK and EGFR inhibitors, may be effective therapies for MF.

First aid for failing flaps.

Wound coverage with pedicled (local, regional, or distant) or free flaps is commonplace throughout plastic surgery. However, irrespective of the method of tissue transfer or type of tissue being transferred, inflow and outflow remain key parameters for success. Much has been written detailing complex tissue transfers and delineating arterial and venous anatomy. Despite this, simple venous insufficiency causing venous congestion is common. In experimental models, when arterial inflow is impaired, even mild venous inadequacy affects flap survival. Furthermore, studies have shown that venous congestion is more detrimental to the rate and percentage of flap area surviving than arterial ischemia. Obviously, complete venous occlusion typically requires operative exploration and correction, but many instances occur when venous congestion occurs for reasons other than complete venous thrombosis. Here we detail the basic postoperative "first aid" techniques available to optimize venous drainage. Although these techniques are not a substitute for sound anatomic flap selection, good surgical technique, or re-operation when a significant underlying problem exists, they do offer additional options to improve flap outcomes.

Induction of apoptosis and transient increase of phosphorylated MAPKs by diallyl disulfide treatment in human nasopharyngeal carcinoma CNE2 cells.

This study was undertaken to elucidate the effect of diallyl disulfide (DADS), an oil-soluble organosulfur compound found in garlic, in suppressing human nasopharyngeal carcinoma cells. A potent increase (of at least 9-fold) in apoptotic cells has accompanied 1) a decrease in cell viability, 2) a increase of the fraction of S-phase cells by up to 63.8%, and 3) a transient increase of the phospho-p38 and phospho-p42/44 (phosphorylated p38 MAPK and phosphorylated p42/44 MAPK) in a time- and concentration-dependent manner. These results indicate that DADS can induce apoptosis in human nasopharyngeal carcinoma cells via, at least partly, S-phase block of the cell cycle, related to a rise in MAPK phosphorylation.