Yessotoxin inhibits phagocytic activity of macrophages

Yessotoxin (YTX) is a sulphated polyether compound produced by some species of dinoflagellate algae, that can be accumulated in bivalve mollusks and ingested by humans upon eating contaminated shellfish. Experiments in mice have demonstrated the lethal effect of YTX after intraperitoneal injection, whereas its oral administration has only limited acute toxicity, coupled with an alteration of plasma membrane protein turnover in the colon of the animals. In vitro studies have shown that this effect is due to the inhibition of endocytosis induced by the toxin. In this work, we investigated the effects of YTX on phagocytosis by using the J774 macrophage cell line. We found that macrophages exposed to 10 or 1 nM YTX display a reduced phagocytic activity against Candida albicans; moreover, phagosome maturation is also inhibited in these cells. Such results were confirmed with resident peritoneal macrophages from normal mice. The inhibition of both phagocytosis and phagosome maturation likely involves cytoskeletal alterations, since a striking rearrangement of the F-actin organization occurs in YTX-treated J774 macrophages. Surprisingly, YTX also enhances cytokine production (TNF-α, MIP-1α and MIP-2) by J774 macrophages. Overall, our results show that low doses of YTX significantly affect both effector and secretory functions of macrophages.     

Incidence and mortality trends for four major cancers in the elderly and middle-aged adults: An international comparison

BackgroundTime trends comparisons by age are important to understand the specific needs of elderly cancer patients and to improve clinical procedures. The aim is to compare 1998–2005 cancer incidence and mortality trends in Italy and the US for both sexes and for two age groups, namely 50–69 year old and 70+ year old.MethodsCancer incidence and mortality data came from 22 Cancer Registries (CRs) of the Italian association of cancer registries (AIRTUM), while the US incidence records were provided by 13 SEER CRs and the mortality statistics provided by the WHO Database. Trends were analysed by the Joinpoint Regression Program in order to obtain Annual Percent Changes and Joinpoints.ResultsColorectal cancer incidence trends were favourable in the US for both sexes and in both age groups, whilst the rates increased in Italian elderly individuals and mortality rates fell markedly only in the US. For lung cancer, incidence and mortality decreased in men but increased in women in the two geographical areas. Breast cancer incidence and mortality declined both in Italy and the US for younger women, but the trends were less favourable in the Italian elderly individuals. The increase of prostate incidence slowed down and mortality diminished for every age group in the US, whilst in Italy only in the younger group.ConclusionsFor major cancers, the Italian elderly experienced less favourable trends than the middle-aged patients whereas, in the US, the trends were similar for both age groups and favourable also for the elderly.     

Plasma and dietary vitamin C levels and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)

Vitamin C is an antioxidant and inhibitor of carcinogenic N-nitroso compound production in the stomach. Higher dietary vitamin C consumption is associated with decreased risk of gastric cancer (GC) in numerous case-control studies, but data from prospective studies are limited, particularly so for blood measures of vitamin C. The objective of this study was to determine the association of plasma and dietary vitamin C levels with the risk of GC in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 European countries. Using a fluorometric method, vitamin C was measured in pre-diagnostic plasma from 215 GC cases (matched controls = 416). Conditional logistic regression models adjusted by body mass index, total energy intake, smoking status/duration/intensity and Helicobacter pylori infection status were used to estimate relative cancer risks. No association with GC risk was observed for dietary vitamin C, whereas an inverse GC risk was observed in the highest versus lowest quartile of plasma vitamin C [odds ratio (OR) = 0.55, 95% confidence interval (CI) = 0.31-0.97, P(trend) = 0.043], which was maintained after exclusion of cases with 相似文献   

Italian mediterranean index and risk of colorectal cancer in the Italian section of the EPIC cohort

Colorectal cancer is among the commonest cancers worldwide. Dietary factors have been linked to colorectal cancer risk, however, few studies have evaluated the relationship between a priori dietary patterns and colorectal cancer risk. We evaluated the effect of adherence to a Mediterranean dietary pattern, as measured by the Italian Mediterranean Index, on the risk of colorectal cancer in the 45,275 participants of the Italian section of the EPIC study who completed a dietary questionnaire. Hazard ratios (HRs) with 95% confidence intervals (CIs) for colorectal cancer in relation to categories of Italian Mediterranean Index score were estimated by multivariate Cox models adjusted for known risk factors, on the whole cohort, on men and women and according to cancer subsite. During a mean follow‐up of 11.28 years, 435 colorectal cancer cases were identified. The Italian Mediterranean Index was inversely associated with colorectal cancer risk (HR: 0.50; 95% CI: 0.35–0.71 for the highest category compared to the lowest, P‐trend: 0.043). Results did not differ by sex. Highest Italian Mediterranean Index score was also significantly associated with reduced risks of any colon cancer (HR: 0.54, 95% CI: 0.36–0.81), distal colon cancer (HR: 0.44, 95% CI: 0.26–0.75) and rectal cancer (HR: 0.41, 95% CI: 0.20–0.81), but not of proximal colon cancer. These findings suggest that adherence to a Mediterranean diet (as measured by the Italian Mediterranean Index) protects against colorectal cancer in general but not against cancer developing in the proximal colon.     

The effect of occasional smoking on smoking-related cancers

Objective

Most studies on tobacco smoking have focused on daily-smokers. Occasional smokers, who have never smoked daily, have often been included in the reference group of never-smokers. We have investigated the association between occasional smoking and cancer of the bladder, kidney, pancreas, upper aero-digestive tract and lung.

Methods

The study population consisted of 158,488 persons, who provided information on occasional smoking, within the European Prospective Investigation into Cancer and Nutrition (EPIC), 780 of whom developed a smoking-related cancer. We used Cox proportional hazard model, stratified by gender and country to estimate incidence rate ratios (IRR) for smoking-related cancers.

Results

The results suggest that occasional smokers have a higher risk of bladder cancer (IRR: 1.92, 95% confidence interval (CI) 0.93–3.98) and of the major smoking-related cancers combined (IRR: 1.24, 95% CI 0.80–1.94) than true never-smokers. Including occasional smokers in the reference group resulted in a lower risk estimate for former and current smokers.

Conclusions

Occasional smoking should be discouraged.     

Anti‐Müllerian hormone and risk of ovarian cancer in nine cohorts

Animal and experimental data suggest that anti‐Müllerian hormone (AMH) serves as a marker of ovarian reserve and inhibits the growth of ovarian tumors. However, few epidemiologic studies have examined the association between AMH and ovarian cancer risk. We conducted a nested case‐control study of 302 ovarian cancer cases and 336 matched controls from nine cohorts. Prediagnostic blood samples of premenopausal women were assayed for AMH using a picoAMH enzyme‐linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable‐adjusted conditional logistic regression. AMH concentration was not associated with overall ovarian cancer risk. The multivariable‐adjusted OR (95% CI), comparing the highest to the lowest quartile of AMH, was 0.99 (0.59–1.67) (P_trend: 0.91). The association did not differ by age at blood draw or oral contraceptive use (all P_{heterogeneity}: ≥0.26). There also was no evidence for heterogeneity of risk for tumors defined by histologic developmental pathway, stage, and grade, and by age at diagnosis and time between blood draw and diagnosis (all P_{heterogeneity}: ≥0.39). In conclusion, this analysis of mostly late premenopausal women from nine cohorts does not support the hypothesized inverse association between prediagnostic circulating levels of AMH and risk of ovarian cancer.     

Ovarian cancer early detection by circulating CA125 in the context of anti‐CA125 autoantibody levels: Results from the EPIC cohort

CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non‐cases. Anti‐CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether these antibodies (1) can serve as early detection markers, providing evidence of an immune response to a developing tumor, and (2) modify the discriminatory capacity of CA125 by either masking CA125 levels (resulting in lower discrimination) or acting synergistically to improve discrimination between cases and non‐cases. We investigated these objectives using a nested case–control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to four matched controls. Circulating CA125 antigen and antibody levels were quantified using an electrochemiluminescence assay. Adjusted areas under the curve (aAUCs) by 2‐year lag‐time intervals were calculated using conditional logistic regression calibrated toward the absolute risk estimates from a pre‐existing epidemiological risk model as an offset‐variable. Anti‐CA125 levels alone did not discriminate cases from controls. For cases diagnosed <2 years after blood collection, discrimination by CA125 antigen was suggestively higher with higher anti‐CA125 levels (aAUC, highest antibody tertile: 0.84 [0.76–0.92]; lowest tertile: 0.76 [0.67–0.86]; p_het = 0.06). We provide the first evidence of potentially synergistic discrimination effects of CA125 and anti‐CA125 antibodies in ovarian early detection. If these findings are replicated, evaluating CA125 in the context of its antibody may improve ovarian cancer early detection.     

Contemporary Assessment of Survival Rates in Stage I Testicular Seminoma: A Population-Based Comparison Between Surveillance and Active Treatment After Orchiectomy

BackgroundWe tested contemporary surveillance and active treatment (AT) that included chemotherapy (CHT) and radiotherapy (RT) rates for stage I testicular seminoma patients, as well as cancer-specific mortality (CSM) and other-cause mortality (OCM) rates.Patients and MethodsWithin the Surveillance, Epidemiology, and End Results database (1988-2015) we identified 11,206 stage I testicular seminoma patients. Surveillance versus CHT versus RT use rates were investigated using estimated annual percentage change (EAPC) analyses. After propensity score (PS) matching, cumulative incidence plots and multivariable competing risks regression models (MCRRMs) tested for CSM and OCM.ResultsOf all 11,206 patients, 4434 (40%), 918 (8%), and 5854 (52%), respectively, underwent surveillance, CHT, or RT after initial orchiectomy. Surveillance (EAPC: 7.5%; P < .001) and CHT (EAPC: 13.5%; P < .001) rates increased over time, whereas RT rates decreased (EAPC: ?3.8%; P < .001). After PS matching, in MCRRMs surveillance was an independent predictor of CSM, relative to AT (hazard ratio [HR], 2.59; P = .04). Conversely, surveillance versus AT did not affect OCM (HR, 1.52; P = .051). All other analyses that focused on CSM and OCM, namely surveillance versus RT, surveillance versus CHT, and RT versus CHT resulted in nonsignificant differences (all P > .5).ConclusionSurveillance and CHT use in stage I testicular seminoma rates increased, whereas RT rate decreased over time. A protective effect of AT defined as either RT or CHT was identified on CSM, relative to surveillance. This protective effect was not described for OCM. No differences in survival were recorded, when individual management strategies (surveillance vs. RT vs. CHT) were compared with each other.     

EGFR ligands as pharmacodynamic biomarkers in metastatic colorectal cancer patients treated with cetuximab and irinotecan

This study was conducted to describe the modulation of plasma epidermal growth factor receptor (EGFR) ligands in EGFR-positive metastatic colorectal cancer (mCRC) patients during treatment with cetuximab and irinotecan and to explore the clinical implication of plasma levels’ variations as potential biomarkers of benefit. Plasma amphiregulin (AR), epidermal growth factor (EGF), transforming growth factor-α, and heparin binding-EGF were assessed by ELISA in 45 chemorefractory mCRC patients, treated with cetuximab and irinotecan. Plasma levels were measured before and 1 h after the first administration of cetuximab, before and 1 h after the second administration, and before the third and the fifth cycles. KRAS and BRAF mutational status were determined. EGFR ligands’ levels were differently modulated according to tumor KRAS and BRAF mutational status. In KRAS wild-type patients (n?=?34), AR and EGF early increased and higher increases were significantly associated with worse clinical outcome. By adopting a specific cut-off value, patients with higher levels of AR 1 h after the first administration had significantly worse response rate, progression free survival, and overall survival. This hypothesis-generating study shows that EGFR ligands are significantly modulated by cetuximab plus irinotecan according to KRAS and BRAF mutational status, and they warrant further investigation as pharmacodynamic markers of resistance to anti-EGFRs.     

Dietary intake of heme iron and risk of gastric cancer in the European prospective investigation into cancer and nutrition study

Even though recent studies suggest that a high intake of heme iron is associated with several types of cancer, epidemiological studies in relation to gastric cancer (GC) are lacking. Our previous results show a positive association between red and processed meat and non cardia gastric cancer, especially in Helicobacter pylori infected subjects. The aim of the study is to investigate the association between heme iron intake and GC risk in the European prospective investigation into cancer and nutrition (EURGAST-EPIC). Dietary intake was assessed by validated center-specific questionnaires. Heme iron was calculated as a type-specific percentage of the total iron content in meat intake, derived from the literature. Antibodies of H. pylori infection and vitamin C levels were measured in a sub-sample of cases and matched controls included in a nested case-control study within the cohort. The study included 481,419 individuals and 444 incident cases of GC that occurred during an average of 8.7 years of followup. We observed a statistically significant association between heme iron intake and GC risk (HR 1.13 95% CI: 1.01-1.26 for a doubling of intake) adjusted by sex, age, BMI, education level, tobacco smoking and energy intake. The positive association between heme iron and the risk of GC was statistically significant in subjects with plasma vitamin C <39 mmol/l only (log2 HR 1.54 95% CI (1.01-2.35). We found a positive association between heme iron intake and gastric cancer risk.