Pre-radiotherapy plasma carotenoids and markers of oxidative stress are associated with survival in head and neck squamous cell carcinoma patients: a prospective study

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to compare plasma levels of antioxidants and oxidative stress biomarkers in head and neck squamous cell carcinoma (HNSCC) patients with healthy controls. Furthermore, the effect of radiotherapy on these biomarkers and their association with survival in HNSCC patients were investigated.</p> <p>Methods</p> <p>Seventy-eight HNSCC patients and 100 healthy controls were included in this study. Follow-up samples at the end of radiotherapy were obtained in 60 patients. Fifteen antioxidant biomarkers (6 carotenoids, 4 tocopherols, ascorbic acid, total antioxidant capacity, glutathione redox potential, total glutathione and total cysteine) and four oxidative stress biomarkers (total hydroperoxides, γ-glutamyl transpeptidase, 8-isoprostagladin F_2αand ratio of oxidized/total ascorbic acid) were measured in plasma samples. Analysis of Covariance was used to compare biomarkers between patients and healthy controls. Kaplan-Meier plots and Cox' proportional hazards models were used to study survival among patients.</p> <p>Results</p> <p>Dietary antioxidants (carotenoids, tocopherols and ascorbic acid), ferric reducing antioxidant power (FRAP) and modified FRAP were lower in HNSCC patients compared to controls and dietary antioxidants decreased during radiotherapy. Total hydroperoxides (d-ROMs), a marker for oxidative stress, were higher in HNSCC patients compared to controls and increased during radiotherapy. Among the biomarkers analyzed, high levels of plasma carotenoids before radiotherapy are associated with a prolonged progression-free survival (hazard rate ratio: 0.42, 95% CI: 0.20-0.91, p = 0.03). Additionally, high relative increase in plasma levels of d-ROMs (hazard rate ratio: 0.31, 95% CI: 0.13-0.76, p = 0.01) and high relative decrease in FRAP (hazard rate ratio: 0.42, 95% CI: 0.17-0.998, p = 0.05) during radiotherapy are also positively associated with survival.</p> <p>Conclusions</p> <p>Biomarkers of antioxidants and oxidative stress are unfavourable in HNSCC patients compared to healthy controls, and radiotherapy affects many of these biomarkers. Increasing levels of antioxidant biomarkers before radiotherapy and increasing oxidative stress during radiotherapy may improve survival indicating that different factors/mechanisms may be important for survival before and during radiotherapy in HNSCC patients. Thus, the therapeutic potential of optimizing antioxidant status and oxidative stress should be explored further in these patients.</p

Cancer chemoprevention: lessons learned and future directions

The concept of delaying or preventing epithelial transformation remains a viable and attainable goal for the future. Drug-based strategies for chemoprevention of the future may predominantly rely upon targeted therapies with tolerable but defined toxicities for treatment of individuals diagnosed with intraepithelial neoplasias. Foods, diet manipulation strategies, or nutraceuticals may be more appropriate to delay or prevent carcinogenesis progression in healthy populations with genetic or epidemiologic evidence of risk for future transformation

Occupational physical activity and risk for prostate cancer in a nationwide cohort study in Sweden

We investigated effects of occupational physical activity on relative risk for prostate cancer. From Swedish nationwide censuses in 1960 and 1970, we defined two cohorts of men whose occupational titles allowed classification of physical activity levels at work in 1960 (n=1 348 971) and in 1970 (n=1 377 629). A third cohort included only men whose jobs required a similar level of physical activity in both 1960 and 1970 (n=673 443). The incidence of prostate cancer between 1971 and 1989 was ascertained through record linkage to the Swedish Cancer Register. A total of 43 836, 28 702, and 19 670 prostate cancers, respectively, occurred in the three cohorts. In all three cohorts, the relative risk for prostate cancer increased with decreasing level of occupational physical activity (P<0.001), using Poisson regression. Among men with the same physical activity levels in 1960 and 1970, the rate ratio was 1.11 for men with sedentary jobs as compared with those whose jobs had very high/high activity levels after adjustment for age at follow-up, calendar year of follow-up and place of residence (95% CI 1.05–1.17; P for trend <0.001). There was no association between occupational activity and prostate cancer mortality. Since we had no data on other potential risk factors the observed associations for both incidence and mortality might have been confounded. Further studies are needed to better understand the potential role of physical activity for prostate cancer

Omega-3 fatty acids in high-risk cardiovascular patients: a meta-analysis of randomized controlled trials

<p>Abstract</p> <p>Background</p> <p>Multiple randomized controlled trials (RCTs) have examined the cardiovascular effects of omega-3 fatty acids and have provided unexplained conflicting results. A meta-analysis of these RCTs to estimate efficacy and safety and potential sources of heterogeneity may be helpful.</p> <p>Methods</p> <p>The Cochrane library, MEDLINE, and EMBASE were systematically searched to identify all interventional trials of omega-3 fatty acids compared to placebo or usual diet in high-risk cardiovascular patients. The primary outcome was all-cause mortality and secondary outcomes were coronary restenosis following percutaneous coronary intervention and safety. Meta-analyses were carried out using Bayesian random-effects models, and heterogeneity was examined using meta-regression.</p> <p>Results</p> <p>A total of 29 RCTs (n = 35,144) met our inclusion criteria, with 25 reporting mortality and 14 reporting restenosis. Omega-3 fatty acids were not associated with a statistically significant decreased mortality (relative risk [RR] = 0.88, 95% Credible Interval [CrI] = 0.64, 1.03) or with restenosis prevention (RR = 0.89, 95% CrI = 0.72, 1.06), though the probability of some benefit remains high (0.93 and 0.90, respectively). However in meta-regressions, there was a >90% probability that larger studies and those with longer follow-up were associated with smaller benefits. No serious safety issues were identified.</p> <p>Conclusions</p> <p>Although not reaching conventional statistical significance, the evidence to date suggests that omega-3 fatty acids may result in a modest reduction in mortality and restenosis. However, caution must be exercised in interpreting these benefits as results were attenuated in higher quality studies, suggesting that bias may be at least partially responsible. Additional high quality studies are required to clarify the role of omega-3 fatty acid supplementation for the secondary prevention of cardiovascular disease.</p