No abstract

Here, we demonstrate that electroporation-enhanced immunization with a rationally designed HPV DNA vaccine (GX-188E), preferentially targeting HPV antigens to dendritic cells, elicits a significant E6/E7-specific IFN-γ-producing T-cell response in all nine cervical intraepithelial neoplasia 3 (CIN3) patients. Importantly, eight out of nine patients exhibit an enhanced polyfunctional HPV-specific CD8 T-cell response as shown by an increase in cytolytic activity, proliferative capacity and secretion of effector molecules. Notably, seven out of nine patients display complete regression of their lesions and viral clearance within 36 weeks of follow up. GX-188E administration does not elicit serious vaccine-associated adverse events at all administered doses. These findings indicate that the magnitude of systemic polyfunctional CD8 T-cell response is the main contributing factor for histological, cytological and virological responses, providing valuable insights into the design of therapeutic vaccines for effectively treating persistent infections and cancers in humans.

Glucose uptake and glycolytic metabolism are enhanced in cancer cells compared to normal cells and tissues. Increased expression of glucose transporter 1 (GLUT1) has been reported in human malignant cells. The aim of this study is to determine the expression of the facilitative glucose transporter protein GLUT1 in human breast carcinomas and a possible correlation between GLUT1 expression and clinical outcome including disease-free or overall survival. One hundred consecutive formalin-fixed, paraffin-embedded sections of invasive breast carcinomas were evaluated by means of immunohistochemical staining of GLUT1. Forty-seven (47%) of 100 breast carcinomas showed positive staining for GLUT1. Expression of GLUT1 correlated significantly with nuclear grade (P < < < <0.001), estrogen receptor status (P = = = =0.002), and progesterone receptor statusThe mean disease-free survival periods of GLUT1-positive and -negative patients were 47 ± ± ± ±2.4 months and 54.3± ± ± ±1.3 months, respectively (P = = = =0.017). The mean overall survival periods of GLUT1-positive and -negative patients were 48.7 ± ± ± ±2.2 and 56.1 ± ± ± ±1.3 months, respectively (P = = = =0.043).In the multivariate analysis, disease-free survival correlated significantly with GLUT1, tumor size, and lymph node involvement (P = = = =0.043, P = = = =0.014, and P = = = =0.045, respectively). In analysis of overall survival, however, lymph node involvement, tumor size, and nuclear grade were statistically significant (P = = = =0.024, P = = = =0.023, and P = = = =0.003, respectively). Our data suggest that absence of GLUT1 expression significantly increases disease-free survival. These findings demonstrate that GLUT1 expression in breast carcinoma can be a marker of aggressive biological behavior and identifies a worse prognosis in breast carcinoma patients.