Effect of Two Aspirin Pretreatment Regimens on Niacin-Induced Cutaneous Reactions

OBJECTIVE: To compare the effects of pretreatment with two aspirin regimens and placebo on niacin-induced cutaneous reactions. DESIGN: Randomized, double-blind, placebo-controlled, crossover study. SETTING: Internal medicine clinic in an academic health center. PARTICIPANTS: Forty-two healthy subjects (22 males and 20 females) between the ages of 35 and 65 (mean age 44.2 years) were recruited and completed the study. Subjects received aspirin 325 mg, aspirin 650 mg, and placebo for 4 consecutive days, and on the fourth day also ingested 500 mg of immediate-release niacin 30 minutes after taking aspirin or placebo. They reported the intensity of flushing, headache, pruritus, tingling, and warmth on a 10-cm visual analogue scale. Reactions were evaluated at time 0 (before the niacin dose), and at 15, 30, 60, and 120 minutes following the niacin dose. Cutaneous reactions were compared at each evaluation time and scored by two other methods. The peak intensity was the highest score recorded at any of the four evaluation times after niacin administration. An intensity-time factor was calculated by totaling the scores of each of the four evaluation times. MEASUREMENT AND MAIN RESULTS: The symptom scores for flushing, itching, tingling, and warmth were all significantly reduced by both aspirin regimens (p < .05 in all cases), although there were no significant differences between the 325-mg and 650-mg doses. The results were similar for each scoring method. CONCLUSIONS: An aspirin regimen of 325 mg is effective in suppressing niacin-induced cutaneous reactions. Increasing the dose to 650 mg does not provide additional benefit

Oncolytic vaccinia virus as a vector for therapeutic sodium iodide symporter gene therapy in prostate cancer

Oncolytic strains of vaccinia virus are currently in clinical development with clear evidence of safety and promising signs of efficacy. Addition of therapeutic genes to the viral genome may increase the therapeutic efficacy of vaccinia. We evaluated the therapeutic potential of vaccinia virus expressing the sodium iodide symporter (NIS) in prostate cancer models, combining oncolysis, external beam radiotherapy and NIS-mediated radioiodide therapy. The NIS-expressing vaccinia virus (VV-NIS), GLV-1h153, was tested in in vitro analyzes of viral cell killing, combination with radiotherapy, NIS expression, cellular radioiodide uptake and apoptotic cell death in PC3, DU145, LNCaP and WPMY-1 human prostate cell lines. In vivo experiments were carried out in PC3 xenografts in CD1 nude mice to assess NIS expression and tumor radioiodide uptake. In addition, the therapeutic benefit of radioiodide treatment in combination with viral oncolysis and external beam radiotherapy was measured. In vitro viral cell killing of prostate cancers was dose-and time-dependent and was through apoptotic mechanisms. Importantly, combined virus therapy and iodizing radiation did not adversely affect oncolysis. NIS gene expression in infected cells was functional and mediated uptake of radioiodide both in vitro and in vivo. Therapy experiments with both xenograft and immunocompetent Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mouse models showed that the addition of radioiodide to VV-NIS-infected tumors was more effective than each single-agent therapy, restricting tumor growth and increasing survival. In conclusion, VV-NIS is effective in prostate cancer models. This treatment modality would be an attractive complement to existing clinical radiotherapy practice