Objective To explore the expressions of CK20, S100A7 and substance P (SP) in different stages of psoriatic lesions and their relationship. Methods A total of 19 patients, who had received irregular treatment for psoriasis and had both progressive and healed psoriatic lesions, were enrolled in this study. Skin tissue specimens were obtained from perilesional normal skin, progressive lesions and healed lesions of these patients and subjected to immunohistochemical analysis of expressions of CK20, S100A7 and SP. Results The relative expression level (absorbance value obtained from immunohistochemical analysis) was 7683.80 ± 6134.55,18305.04 ± 13171.30, 7257.53 ± 4417.75 for CK20, 8789.05 ± 6240.91, 18058.01 ± 16537.18, 9295.65 ±9310.02 for S100A7, 3242.51 ± 3775.41, 9364.98 ± 7596.64, 2910.85 ± 3349.46 for SP, respectively, in normal skin, progressive lesions and healed psoriatic lesions. A significant increase was observed in the expressions of CK20, S100A7 and SP in progressive lesions compared with normal skin and healed lesions, whereas no statistical difference was noted in those between normal skin and healed lesions (P ＞ 0.05 ). The expression of CK20 was positively correlated with that of S100A7 and SP (r = 0.779, 0.876, both P ＜ 0.05 ). Conclusion The pathogenesis of psoriasis seems to be associated with the changes in the number of Merkel cells.

TNF-related apoptosis-inducing ligand (TRAIL) has been proposed as a promising cancer therapy that preferentially induces apoptosis in cancer cells, but not most normal tissues. However, many cancers are resistant to TRAIL by mechanisms that are poorly understood. In this study, we showed that tunicamycin, a naturally occurring antibiotic, was a potent enhancer of TRAIL-induced apoptosis through downregulation of survivin. The tunicamycin-mediated sensitization to TRAIL was efficiently reduced by forced expression of survivin, suggesting that the sensitization was mediated at least in part through inhibition of survivin expression. Tunicamycin also repressed expression of cyclin D1, a cell cycle regulator commonly overexpressed in thyroid carcinoma. Furthermore, silencing cyclin D1 by RNA interference reduced survivin expression and sensitized thyroid cancer cells to TRAIL; in contrast, forced expression of cyclin D1 attenuated tunicamycin-potentiated TRAIL-induced apoptosis via over-riding downregulation of survivin. Collectively, our results demonstrated that tunicamycin promoted TRAIL-induced apoptosis, at least in part, by inhibiting the expression of cyclin D1 and subsequent survivin. Of note, tunicamycin did not sensitize the differentiated thyroid epithelial cells to TRAIL-induced apoptosis. Thus, combined treatment with tunicamycin and TRAIL may offer an attractive strategy for safely treating resistant thyroid cancers.
Anti-Bacterial Agents/*pharmacology ; *Apoptosis ; Cell Line, Tumor ; Cyclin D1/*antagonists & inhibitors/metabolism ; *Down-Regulation ; Humans ; Microtubule-Associated Proteins/*genetics/metabolism ; TNF-Related Apoptosis-Inducing Ligand/*metabolism ; Tunicamycin/*pharmacology

TNF-related apoptosis-inducing ligand (TRAIL) has been proposed as a promising cancer therapy that preferentially induces apoptosis in cancer cells, but not most normal tissues. However, many cancers are resistant to TRAIL by mechanisms that are poorly understood. In this study, we showed that tunicamycin, a naturally occurring antibiotic, was a potent enhancer of TRAIL-induced apoptosis through downregulation of survivin. The tunicamycin-mediated sensitization to TRAIL was efficiently reduced by forced expression of survivin, suggesting that the sensitization was mediated at least in part through inhibition of survivin expression. Tunicamycin also repressed expression of cyclin D1, a cell cycle regulator commonly overexpressed in thyroid carcinoma. Furthermore, silencing cyclin D1 by RNA interference reduced survivin expression and sensitized thyroid cancer cells to TRAIL; in contrast, forced expression of cyclin D1 attenuated tunicamycin-potentiated TRAIL-induced apoptosis via over-riding downregulation of survivin. Collectively, our results demonstrated that tunicamycin promoted TRAIL-induced apoptosis, at least in part, by inhibiting the expression of cyclin D1 and subsequent survivin. Of note, tunicamycin did not sensitize the differentiated thyroid epithelial cells to TRAIL-induced apoptosis. Thus, combined treatment with tunicamycin and TRAIL may offer an attractive strategy for safely treating resistant thyroid cancers.
Anti-Bacterial Agents/*pharmacology ; *Apoptosis ; Cell Line, Tumor ; Cyclin D1/*antagonists & inhibitors/metabolism ; *Down-Regulation ; Humans ; Microtubule-Associated Proteins/*genetics/metabolism ; TNF-Related Apoptosis-Inducing Ligand/*metabolism ; Tunicamycin/*pharmacology