We have investigated the role of antigen-processing machinery (APM) component defects in HLA class I antigen downregulation in laryngeal squamous cell carcinoma (SCC) lesions and assessed the clinical significance of these defects. To this end, 63 formalin-fixed, paraffin-embedded tumor lesions were examined for APM component and HLA class I antigen expression by immunohistochemistry. Calnexin, calreticulin, and ERp57 were down-regulated in f25% of the lesions tested, whereas LMP2, TAP1, tapasin, and HLA class I antigens were down-regulated in at least 70% of the lesions tested. LMP2 and tapasin expression was significantly correlated with HLA class I antigen expression suggesting APM component defects as a mechanism underlying HLA class I antigen downregulation in laryngeal SCC lesions. The expression of most APM components and HLA class I antigens was correlated with the extent of CD8 + T cell infiltration into tumor lesions. Furthermore, LMP2 and HLA class I antigen down-regulation and low CD8 + T cell infiltration were significantly associated with reduced patients' survival. Multivariate analysis identified HLA class I antigen down-regulation as an independent unfavorable prognostic marker. This association is likely to reflect the reduction in the extent of CD8 + T cell infiltration in laryngeal SCC lesions. (Cancer Res 2006; 66(18): 9281-9)

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The purpose of this study was to investigate the hypothesis that electrical stimulation regulates the levels of gene expression related to apoptosis in denervated muscle and prevents muscle atrophy after denervation. Nineteen rats were used in this study. To denervate soleus muscle, sciatic nerve was resected under aseptic condition. Electrical stimulation with 4 mA rectangular pulses of 0.5 ms duration at 2 Hz lasting for 1 hour was delivered to lower limb including the soleus muscle using two surface electrodes. After the stimulation periods of 4 weeks, the levels of gene expression related to apoptosis were evaluated. Electrical stimulation increased valosin-containing protein (VCP) expression and decreased cleaved caspase-12 expression in denervated muscles. These results indicated that electrical stimulation to denervated muscle suppresses ER-specific apoptosis by enhancing VCP expression. We proposed that electrical stimulation would be a potential treatment for preventing atrophy of denervated skeletal muscles.

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