Here we report a long-term persistence of HIV-1 structural proteins and glycoproteins in germinal centers (GCs) of lymph nodes (LNs) in the absence of detectable virus replication in patients under highly active antiretroviral therapy (HAART). The persistence of viral structural proteins and glycoproteins in GCs was accompanied by specific antibody responses to HIV-1. Seven patients during the chronic phase of HIV-1 infection were analyzed for the presence of the capsid protein (HIV-1p24), matrix protein (HIV-1p17), and envelope glycoproteins (HIV-1gp120͞gp41), as well as for viral RNA (vRNA) in biopsy specimens from LNs obtained before initiation of therapy and during HAART that lasted from 5 to 13 months. In parallel, these patients were also monitored for viremia and specific anti-HIV-1 antibody responses to structural proteins and glycoproteins both before and during treatment. Before-therapy viral levels, as determined by RT-PCR, ranged from 3 ؋ 10 3 to 6.3 ؋ 10 5 copies of vRNA per ml, whereas during treatment, vRNA was under detectable levels (<25 copies per ml). The pattern of vRNA detection in peripheral blood was concordant with in situ hybridization results of LN specimens. Before treatment, vRNA associated with follicular dendritic cells (FDCs) was readily detected in GCs of LNs of the patients, whereas during therapy, vRNA was consistently absent in the GCs of LN biopsies of treated patients. In contrast to vRNA hybridization results, viral structural proteins and glycoproteins, evaluated by immunohistochemical staining, were present and persisted in the GC light zone of LNs in abundant amounts not only before initiation of therapy but also during HAART, when no vRNA was detected in GCs. Consistent with immunohistochemical findings, specific antibody responses to HIV1p17, -p24, and -gp120͞gp41, as evaluated by ELISA and virus neutralization, persisted in patients under therapy for up to 13 months of follow-up. The implications of these findings are discussed in relation to HIV-1 persistence in infected individuals and the potential role of chronic antigenic stimulation by the deposited structural proteins in GCs for AIDS-associated B cell malignancies.

Background Few studies have examined the relationship of lifestyle factors with mortality among colorectal cancer patients. Methods Among NIH-AARP Diet and Health study participants we identified 4,213 colon and 1,514 rectal cancer cases through linkage to state cancer registries and determined date and cause of death using the National Death Index. Lifestyle factors were assessed at baseline and included: healthy diet (measured by Healthy Eating Index 2005; HEI-2005), body mass index (BMI), physical activity, alcohol consumption and smoking. We examined the association of factors individually and combined into a lifestyle score with five-year mortality from all-causes, colorectal cancer, and cardiovascular disease (CVD). We estimated relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards models. Results Among colon cancer survivors, smokers had increased risk of total mortality (RR 1.74; 95% CI 1.45–2.08) and colorectal cancer mortality (1.46; 1.17–1.82), compared to never smokers. Obese (BMI ≥30) individuals had increased risk of all death (1.19; 1.02–1.39) and CVD death (1.84; 1.05–3.23), compared to normal weight (BMI 18.5 to <25) individuals. Compared to those with the lowest lifestyle score, those with the highest score had a 34% lower risk of all-cause mortality (0.66; 0.50–0.87). Among rectal cancer survivors, individuals in the highest quintile of HEI-2005 scores had reduced all-cause mortality (0.60; 0.42–0.86) compared to those in the lowest. Higher combined lifestyle scores were associated with a 46% lower risk of total mortality (0.54; 0.32–0.91). Conclusion Healthier lifestyle before cancer diagnosis was associated with improved overall survival after diagnosis with colorectal cancer.

Background Observational studies report inconsistent associations of fat and fatty acids with prostate cancer. Methods We investigated associations between dietary fats and fatty acids and risk of prostate cancer in the National Institutes of Health (NIH)-AARP Diet and Health Study. Diet was assessed at baseline with self-administered food-frequency questionnaires. Cases were determined by linkage with state cancer registries. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models. Results Among 288,268 men with average follow-up of 9 years, 23,281 prostate cancer cases (18,934 non-advanced and 2,930 advanced including 725 fatal cases) were identified. Total fat, and mono- and polyunsaturated fat INTAKES were not associated with incidence of prostate cancer. Saturated fat intake was related to increased risk of advanced prostate cancer (HRQuintile 5 vs. Qunitile 1 (Q1 vs. Q5)1.21; 95% CI 1.00–1.46; p-for-trend=0.03) and fatal prostate cancer (HR Q5 vs. Q1 1.47; 95% CI 1.01–2.15; p-for-trend=0.04). Alpha-linolenic acid (ALA) intake was related to increased risk of advanced prostate cancer (HRQ5 vs. Q1 1.17; 95 % CI:1.04–1.31; p-for-trend 0.01). Eicosapentanoic acid (EPA) intake was related to decreased risk of fatal prostate cancer (HR Q5 vs. Q1 0.82; 95% CI 0.64–1.04; p-for-trend 0.02). Conclusion Our study suggests that the associations of fat and fatty acids differ by prostate cancer severity. Saturated fat, ALA and EPA intakes were related to the risk of advanced or fatal prostate cancer, but not to non-advanced prostate cancer. Impact identifying factors associated with advanced prostate cancer could reduce morbidity and mortality.