Epstein-Barr virus (EBV) is associated with several malignancies including nasopharyngeal carcinoma, a high incidence tumor in Chinese populations, in which tumor cells express the two EBV antigens EB nuclear antigen 1 (EBNA1) and latent membrane protein 2 (LMP2). Here, we report the phase I trial of a recombinant vaccinia virus, MVA-EL, which encodes an EBNA1/LMP2 fusion protein designed to boost T-cell immunity to these antigens. The vaccine was delivered to Hong Kong patients with nasopharyngeal carcinoma to determine a safe and immunogenic dose. The patients, all in remission more than 12 weeks after primary therapy, received three intradermal MVA-EL vaccinations at three weekly intervals, using five escalating dose levels between 5 Â 10 7 and 5 Â 10 8 plaque-forming unit (pfu). Blood samples were taken during prescreening, immediately before vaccination, one week afterward and at intervals up to one year later. Immunogenicity was tested by IFN-g ELIspot assays using complete EBNA1 and LMP2 15-mer peptide mixes and known epitope peptides relevant to patient MHC type. Eighteen patients were treated, three per dose level one to four and six at the highest dose, without dose-limiting toxicity. T-cell responses to one or both vaccine antigens were increased in 15 of 18 patients and, in many cases, were mapped to known CD4 and CD8 epitopes in EBNA1 and/or LMP2. The range of these responses suggested a direct relationship with vaccine dose, with all six patients at the highest dose level giving strong EBNA1/LMP2 responses. We concluded that MVA-EL is both safe and immunogenic, allowing the highest dose to be forwarded to phase II studies examining clinical benefit. Cancer Res; 73(6); 1676-88. Ó2012 AACR.

Background: Golgi anti-apoptotic protein (GAAP) is a regulator of intracellular Ca 2+ fluxes and apoptosis. Results: The transmembrane topology of viral GAAP is conserved in human GAAP and BI-1. Conclusion: GAAPs and BI-1 have a six membrane-spanning topology with cytosolic N and C termini and a C-terminal reentrant loop. Significance: The topology of the TMBIM family provides valuable structural information on these proteins.

hGAAP promotes cell adhesion and migration by increasing localized Ca2+-dependent activation of calpain, leading to increased focal adhesion dynamics.

Two decades of research into the role of immunosuppression and angiogenesis in tumor biology have revealed multiple links between the two. Vascular endothelial growth factor, originally thought to be solely involved in vascular growth and permeability, has emerged as a significant agent of immune tolerance in the tumor microenvironment. This review examines two major elements of this field: the research behind the role of vascular endothelial growth factor in immunosuppression, especially as pertains to dendritic cell function; and the subsequent research into the potential for using antiangiogenic therapy to both starve tumors by hypoxia and enhance the response of tumors to immunotherapy. Several strategies tested so far have yielded incomplete, yet promising, results.

Many individuals involved in the sport of powerlifting believe that the squat and deadlift have such similar lifting characteristics that the lifts yield comparable training results. The aim of this study was to compare and contrast biomechanical parameters between the conventional style deadlift and the back squat performed by 25 lifters competing in regional powerlifting championship. The 3-dimensional analysis incorporated 4 60 Hz synchronized video cameras for collecting data from 25 participants. Parameters were quantified at the sticking point specific to each lift. Kinematic variables were calculated at the hip, knee, and ankle. Paired (samples) t-tests were used to detect significant differences in the kinematic mean scores for the different lift types. The statistical analysis revealed significant differences exist between the squat (0.09 m/s) and the deadlift (0.20 m/s) vertical bar velocities. Differences were found for angular position of the hip, knee, and ankle between lifts. The sticking point thigh angles were quantified as 32.54 +/- 3.02 and 57.42 +/- 4.57 for the squat and deadlift, respectively. Trunk angles were 40.58 +/- 6.29 (squat) and 58.30 +/- 7.15 (deadlift). The results indicate the back squat represents a synergistic or simultaneous movement, whereas the deadlift demonstrates a sequential or segmented movement. The kinematic analysis of the squat and the conventional deadlift indicate that the individual lifts are markedly different (p < 0.01), implying that no direct or specific cross-over effect exists between the individual lifts.