14-3-3 eta depletion sensitizes glioblastoma cells to irradiation due to enhanced mitotic cell death.

14-3-3 proteins have important roles in several cellular processes such as cell cycle progression, the DNA-damage checkpoint and apoptosis. We have shown previously that depleting 14-3-3η, a 14-3-3 isoform, enhances mitotic cell death, and that combining it with microtubule agents is more effective for anticancer therapeutics. In this study, we investigated whether depleting 14-3-3η can be combined with radiotherapy to enhance its therapeutic efficacy. We found that depleting 14-3-3η resulted in a synergistic radiosensitizing effect when combined with radiotherapy in several glioblastoma cell lines, where its specific expression and correlation of its expression level with malignancy have been reported. The radiosensitizing effect was associated with enhanced mitotic cell death by 14-3-3η depletion but not with mitotic catastrophe, which is one of the major cell death mechanisms observed in response to irradiation of most solid tumors. These results suggest that 14-3-3η may be a therapeutic target to overcome radioresistance in glioblastoma.

Prognostic stratification using F-18 FDG PET/CT in patients with advanced stage (stage III and IV) non-small cell lung cancer.

F-18 FDG PET could provide prognostic information in patients with advanced resectable NSCLC. In the current study, we investigated the prognostic implication of F-18 FDG PET after chemotherapy in patients with advanced stage III and IV NSCLC. A retrospective review identified 19 patients with advanced stage (stage III and IV) NSCLC who received F-18 FDG PET/CT at diagnosis of cancer and after chemotherapy. The visual response and changes of SUV max before and after treatment on survival was investigated using Kaplan-Meier and Cox proportional hazard regression analyses. The median follow-up time was overall 24.8 month (range, 9.4-59.8 month), for surviving patients 41 month (range, 34.1-59.8 month), and for deceased patients 16.6 month (range, 9.4-29.4 month). Overall survival after baseline F-18 FDG PET/CT at 1 year was 73.7% and at 2 year was 47.4%. Comparing patients with and without F-18 FDG PET/CT response, there was statistically significant difference in overall survival between the 2 groups (median survival time, responder, 29.4 month; non-responder, 14.2 month, Chi(2)=3.91, p=0.048). Also, using the %DeltaSUV(max) for the comparison, significant difference was existed in overall survival between 2 groups (Chi(2)=12.6, p=0.0004). When the tumor reveals more than 17.85% reduction of %DeltaSUV(max), the survival could be predicted (AUC, 0857; standard error, 0.0866; 95% confidence interval, 0.622-0.971; sensitivity, 75%; specificity, 100%; p=0.0001). With Cox proportional hazard model, %DeltaSUV(max) was determined to be a potent prognostic factor for survival (Chi(2), 12.09; p=0.0005). In conclusion, using the visual and quantitative analyses of F-18 FDG PET/CT, the responder to chemotherapy in advanced stage NSCLC patients had a better prognosis. Moreover, the potent predictor of prognosis in advanced stage NSCLC patients was %DeltaSUV(max).

A novel factor isolated from Actinobacillus actinomycetemcomitans stimulates mouse B cells and human peripheral blood mononuclear cells.

A novel immunostimulating factor (ISTF) of Actinobacillus actinomycetemcomitans ATCC 29522 was isolated and characterized as inducing proliferation of mouse B cells and human peripheral blood mononuclear cells. This factor was isolated from the bacterial culture medium and purified by size exclusion chromatography, dye-ligand affinity chromatography, immunoaffinity chromatography using monoclonal antibodies, and preparative electrophoresis. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the purified ISTF migrated as a single band corresponding to a molecular mass of 13 kDa. ISTF was a proteinaceous material distinct from lipopolysaccharide; it directly induced the proliferation of B lymphocytes but had no effect on the proliferation of T lymphocytes, even in the presence of antigen-presenting cells. A B-lymphocyte-mitogenic activity of ISTF was also shown by flow cytometric analysis of responding cell subpopulations. Immunoblot analysis revealed that ISTF was a component of the outer membranes of bacteria, could exist as a soluble form, and was released by growing and/or lysed bacteria. These results suggest that ISTF produced by A. actinomycetemcomitans may play an important role in immunopathologic changes associated with A. actinomycetemcomitans infections.