Background:Prostate-specific antigen (PSA) screening has low specificity. Assessment of methylation status in body fluids may complement PSA screening if the test has high specificity.Method:The purpose of this study was to conduct a meta-analysis of the sensitivity and specificity for prostate cancer detection of glutathione-s-transferase–π (GSTP1) methylation in body fluids (plasma, serum, whole blood, urine, ejaculate, and prostatic secretions). We conducted a comprehensive literature search on Medline (Pubmed). We included studies if they met all four of the following criteria: (1) measurement of DNA methylation in body fluids; (2) a case-control or case-only design; (3) publication in an English journal; and (4) adult subjects. Reviewers conducted data extraction independently using a standardised protocol. Twenty-two studies were finally included in this paper. Primer sequences and methylation method in each study were summarised and evaluated using meta-analyses. This paper represents a unique cross-disciplinary approach to molecular epidemiology.Results:The pooled specificity of GSTP1 promoter methylation measured in plasma, serum, and urine samples from negative-biopsy controls was 0.89 (95% CI, 0.80–0.95). Stratified analyses consistently showed a high specificity across different sample types and methylation methods (include both primer sequences and location). The pooled sensitivity was 0.52 (95% CI, 0.40–0.64).Conclusions:The pooled specificity of GSTP1 promoter methylation measures in plasma, serum, and urine was excellent and much higher than the specificity of PSA. The sensitivity of GSTP1 was modest, no higher than that of PSA. These results suggest that measurement of GSTP1 promoter methylation in plasma, serum, or urine samples may complement PSA screening for prostate cancer diagnosis.

Introduction Biomarkers of oxidative stress and advanced glycation end products (AGE) have been linked to the development of prostate cancer, but evidence from human studies is either scarce or controversial. Materials and Methods We conducted a prospective nested case-control study among 48 men (24 prostate cancer cases and 24 controls) aged 48–76 years at baseline. The participants of our study were a part of the Fernald Community Cohort (FCC). Prostate cancer cases and controls were matched individually on age (± 3 years) with 1:1 ratio. Biomarkers included urine F2-isoprostanes (markers of lipid oxidation), plasma fluorescent oxidation products (FlOPs; markers of global oxidation) and carboxymethyllysine (CML; a major end-stage AGE). Results At baseline, cases had similar age, body mass index, proportion of family history of prostate cancer, history of benign prostatic hyperplasia, history of hypertension, history of diabetes, smokers and plasma glucose levels as compared to controls. Levels of plasma CML were significantly higher in cases than in controls (182 vs. 152 μg/ml, P < 0.05). In the conditional logistic regression model, an increase in CML equivalent to one standard deviation was associated with increased risk of incident prostate cancer (Relative risk = 1.79, 95% confidence interval = 1.00–3.21), and accounted for ~8% variance of prostate cancer liability. Urine F2-isoprostanes and plasma FlOPs were not associated with prostate cancer incidence. Conclusion Higher levels of plasma CML were associated with increased risk of prostate cancer. This suggests a potential new pathway for prostate cancer prediction and treatment.

Our goal is to apply an anti-idiotype (Id) antibody based vaccine approach for the treatment of Her-2/neu-positive human cancer. Amplification and/or over-expression of Her-2/neu occur in multiple human malignancies and are associated with poor prognosis. Her-2/neu proto-oncogene is a suitable target for cancer immunotherapy. We have developed and characterized a murine monoclonal anti-Id antibody, 6D12 that mimics a specific epitope of Her-2/neu and can be used as a surrogate antigen for Her-2/neu. In this study, the efficacy of 6D12 as a tumor vaccine was evaluated in a murine tumor model. Immunization of immunocompetent C57BL/6 mice with 6D12 conjugated to keyhole limpet hemocyanin and mixed with Freund's adjuvant or 6D12 combined with the adjuvant QS21 induced anti-6D12 as well as anti-Her-2/neu immunity. Her-2/neu-positive human breast carcinoma cells, SK-BR-3 reacted with immunized mice sera as determined by ELISA and flow cytometry. Flow cytometry analysis also demonstrated strong reactivity of immunized mice sera with human Her-2/neu transfected EL4 cells (EL4-Her-2), but no reactivity with nontransfected parental EL4 cells. Antibody dependent cellular cytotoxicity against EL4-Her-2 cells was also observed in presence of immune sera. Mice immunized with 6D12 were protected against a challenge with lethal doses of EL4-Her-2 cells, whereas no protection was observed against parental EL4 cells or when mice were immunized with an unrelated anti-Id antibody and challenged with EL4-Her-2 cells. These data suggest that anti-Id 6D12 vaccine can induce protective Her-2/neu specific antitumor immunity and may serve as a potential network antigen for the treatment of patients with Her-2/neu-positive tumors.