Fowlpox virus recombinants expressing HPV-16 E6 and E7 oncogenes for the therapy of cervical carcinoma elicit humoral and cell-mediated responses in rabbits

Background: Around half million new cases of cervical cancer arise each year, making the development of an effective therapeutic vaccine against HPV a high priority. As the E6 and E7 oncoproteins are expressed in all HPV-16 tumour cells, vaccines expressing these proteins might clear an already established tumour and support the treatment of HPV-related precancerous lesions. Methods: Three different immunisation regimens were tested in a pre-clinical trial in rabbits to evaluate the humoral and cell-mediated responses of a putative HPV-16 vaccine. Fowlpoxvirus (FP) recombinants separately expressing the HPV-16 E6 (FPE6) and E7 (FPE7) transgenes were used for priming, followed by E7 protein boosting. Results: All of the protocols were effective in eliciting a high antibody response. This was also confirmed by interleukin-4 production, which increased after simultaneous priming with both FPE6 and FPE7 and after E7 protein boost. A cell-mediated immune response was also detected in most of the animals. Conclusion: These results establish a preliminary profile for the therapy with the combined use of avipox recombinants, which may represent safer immunogens than vaccinia-based vectors in immuno-compromised individuals, as they express the transgenes in most mammalian cells in the absence of a productive replication

Efficacy of B vitamins in lowering homocysteine in older men: Maximal effects for those with B12 deficiency and hyperhomocysteinemia

Background and Purpose— A higher plasma concentration of total homocysteine (tHcy) is associated with a greater risk of cardiovascular events. Previous studies, largely in younger individuals, have shown that B vitamins lowered tHcy by substantial amounts and that this effect is greater in people with higher tHcy and lower folate levels. Methods— We undertook a 2-year, double-blind, placebo-controlled, randomized trial in 299 men aged 75 years, comparing treatment with a daily tablet containing 2 mg of folate, 25 mg of B6, and 400 µg of B12 or placebo. The study groups were balanced regarding age (mean±SD, 78.9±2.8 years), B vitamins, and tHcy at baseline. Results— Among the 13% with B12 deficiency, the difference in mean changes in treatment and control groups for tHcy was 6.74 µmol/L (95% CI, 3.94 to 9.55 µmol/L) compared with 2.88 µmol/L (95% CI, 0.07 to 5.69 µmol/L) for all others. Among the 20% with hyperhomocysteinaemia, the difference between mean changes in treatment and control groups for men with high plasma tHcy compared with the rest of the group was 2.8 µmol/L (95% CI, 0.6 to 4.9 µmol/L). Baseline vitamin B12, serum folate, and tHcy were significantly associated with changes in plasma tHcy at follow-up (r=0.252, r=0.522, and r=–0.903, respectively; P=0.003, <0.001, and <0.001, respectively) in the vitamin group. Conclusions— The tHcy-lowering effect of B vitamins was maximal in those who had low B12 or high tHcy levels. Community-dwelling older men, who are likely to be deficient in B12 or have hyperhomocysteinemia, may be most likely to benefit from treatment with B vitamins.Leon Flicker, Samuel D. Vasikaran, Jenny Thomas, John M. Acres, Paul Norman, Konrad Jamrozik, Graeme J. Hankey and Osvaldo P. Almeid

Predictors of impaired cognitive function in men over the age of 80 years: results from the Health in Men Study

Leon Flicker, Osvaldo P. Almeida, John Acres, Max T. Q. Le, Raywin J. Tuohy, Konrad Jamrozik, Graeme Hankey and Paul Norma