The Clinical Implications of Death Domain-Associated Protein (DAXX) Expression.

BACKGROUND: Death domain-associated protein (DAXX), originally identified as a pro-apoptotic protein, is now understood to be either a pro-apoptotic or an anti-apoptotic factor with a chromatin remodeler, depending on the cell type and context. This study evaluated DAXX expression and its clinical implications in squamous cell carcinoma of the esophagus. METHODS: Paraffin-embedded tissues from 60 cases of esophageal squamous carcinoma were analyzed immunohistochemically. An immune reaction with more than 10% of tumor cells was interpreted as positive. Positive reactions were sorted into 2 groups: reactions in 11%-50% of tumor cells and reactions in more than 51% of tumor cells, and the correlations between expression and survival and clinical prognosticators were analyzed. RESULTS: Forty-three of the 60 cases (71.7%) showed strong nuclear DAXX expression, among which 19 cases showed a positive reaction (31.7%) in 11%-50% of tumor cells, and 24 cases (40.0%) showed a positive reaction in more than 51% of tumor cells. A negative reaction was found in 17 cases (28.3%). These patterns of immunostaining were significantly associated with the N stage (p=0.005) and American Joint Committee on Cancer stage (p=0.001), but overall survival showed no significant difference. There were no correlations of DAXX expression with age, gender, or T stage. However, in stage IIB (p=0.046) and stage IV (p=0.014) disease, DAXX expression was significantly correlated with survival. CONCLUSION: This investigation found upregulation of DAXX in esophageal cancer, with a 71.7% expression rate. DAXX immunostaining could be used in clinical practice to predict aggressive tumors with lymph node metastasis in advanced-stage disease, especially in stages IIB and IV.

Induction of ER Stress-Mediated Apoptosis by α-Lipoic Acid in A549 Cell Lines.

BACKGROUND: α-Lipoic acid (α-LA) has been studied as an anticancer agent as well as a therapeutic agent for diabetes and obesity. We performed this study to evaluate the anticancer effects and mechanisms of α-LA in a lung cancer cell line, A549. MATERIALS AND METHODS: α-LA-induced apoptosis of A549 cells was detected by fluorescence-activated cell sorting analysis and a DNA fragmentation assay. Expression of apoptosis-related genes was analyzed by western blot and reverse transcription-polymerase chain reaction analyses. RESULTS: α-LA induced apoptosis and DNA fragmentation in A549 cells in a dose- and time-dependent manner. α-LA increased caspase activity and the degradation of poly (ADP-ribose) polymerase. It induced expression of endoplasmic reticulum (ER) stress-related genes, such as glucose-regulated protein 78, C/EBP-homologous protein, and the short form of X-box binding protein-1, and decreased expression of the anti-apoptotic protein, X-linked inhibitor of apoptosis protein. Reactive oxygen species (ROS) production was induced by α-LA, and the antioxidant N-acetyl-L-cysteine decreased the α-LA-induced increase in expression of apoptosis and ER stress-related proteins. CONCLUSION: α-LA induced ER stress-mediated apoptosis in A549 cells via ROS. α-LA may therefore be clinically useful for treating lung cancer.