Role of the Benzodioxole Group in the Interactions between the Natural Alkaloids Chelerythrine and Coptisine and the Human Telomeric G-Quadruplex DNA. A Multiapproach Investigation.

The binding properties toward the human telomeric G-quadruplex of the two natural alkaloids coptisine and chelerythrine were studied using spectroscopic techniques, molecular modeling, and X-ray diffraction analysis. The results were compared with reported data for the parent compounds berberine and sanguinarine. Spectroscopic studies showed modest, but different rearrangements of the DNA-ligand complexes, which can be explained considering particular stereochemical features for these alkaloids, in spite of the similarity of their skeletons. In fact, the presence of a dioxolo moiety rather than the two methoxy functions improves the efficiency of coptisine and sanguinarine in comparison to berberine and chelerythrine, and the overall stability trend is sanguinarine > chelerythrine ≈ coptisine > berberine. Accordingly, the X-ray diffraction analysis confirmed the involvement of the benzodioxolo groups in the coptisine/DNA binding by means of π···π, O···π, and CH···O interactions. Similar information is provided by modeling studies, which, additionally, evidenced reasons for the quadruplex vs double-helix selectivity shown by these alkaloids. Thus, the analyses shed light on the key role of the benzodioxolo moieties in strengthening the interaction with the G4-folded human telomeric sequence and indicated the superior G4 stabilizing properties of the benzophenanthridine scaffold with respect to the protoberberine one and conversely the better G4 vs dsDNA selectivity profile of coptisine over the other alkaloids.

Vitamin E intake from natural sources and head and neck cancer risk: a pooled analysis in the International Head and Neck Cancer Epidemiology consortium.

BACKGROUND: Evidence for the possible effect of vitamin E on head and neck cancers (HNCs) is limited. METHODS: We used individual-level pooled data from 10 case-control studies (5959 cases and 12 248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium to assess the association between vitamin E intake from natural sources and cancer of the oral cavity/pharynx and larynx. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models applied to quintile categories of non-alcohol energy-adjusted vitamin E intake. RESULTS: Intake of vitamin E was inversely related to oral/pharyngeal cancer (OR for the fifth vs the first quintile category=0.59, 95% CI: 0.49-0.71; P for trend <0.001) and to laryngeal cancer (OR=0.67, 95% CI: 0.54-0.83, P for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral/pharyngeal cancer. Inverse associations were generally observed for the anatomical subsites of oral and pharyngeal cancer and within covariate strata for both sites. CONCLUSION: Our findings suggest that greater vitamin E intake from foods may lower HNC risk, although we were not able to explain the heterogeneity observed across studies or rule out certain sources of bias.

Nutrient-based dietary patterns and nasopharyngeal cancer: evidence from an exploratory factor analysis.

BACKGROUND: To our knowledge, no study assessed the association between dietary patterns and nasopharyngeal carcinoma (NPC) in low-incidence areas. METHODS: We examined this association in a hospital-based case-control study carried out in Italy between 1992 and 2008, including 198 incident NPC cases and 594 controls. A posteriori dietary patterns were identified through principal component factor analysis performed on 28 nutrients and minerals derived from a 78-item food-frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models on tertiles of factor scores. RESULTS: We identified five dietary patterns named Animal products, Starch-rich, Vitamins and fibre, Animal unsaturated fatty acids (AUFAs), and Vegetable unsaturated fatty acids (VUFAs). The Animal product (OR=2.62, 95% CI=1.67-4.13, for the highest vs lowest score tertile), Starch-rich (OR=2.05, 95% CI=1.27-3.33), and VUFA (OR=1.90, 95% CI=1.22-2.96) patterns were positively associated with NPC. The AUFA pattern showed a positive association of borderline significance, whereas the Vitamins and fibre pattern was nonsignificantly but inversely associated with NPC. CONCLUSIONS: These findings suggest that diets rich in animal products, starch, and fats are positively related to NPC risk in this low-incidence country.

Efficacy of cosmetic products in cellulite reduction: systematic review and meta-analysis.

BACKGROUND: The number of original articles investigating the efficacy of cosmetic products in cellulite reduction increased rapidly in the last decade; however, to our knowledge, no systematic review and meta-analysis has been performed so far. OBJECTIVE: We conducted a systematic review of in vivo studies on humans adopting the PRISMA guidelines. Moreover, we used a meta-analytic approach to estimate the overall effect of cosmetic creams in cellulite treatment from controlled trials with more than 10 patients per arm, using thigh circumference reduction as the outcome measure. METHODS: Medline and Embase were searched up to August 2012 to identify eligible studies. RESULTS: Twenty-one original studies were included in the present systematic review. All studies were clinical trials, most of them recruited women only and 67% had an intra-patient study design. About half of the active cosmetic creams tested only contained one active ingredient among xanthenes, herbals or retinoids. The other studies tested cosmetic creams with more complex formulations and most of them included xanthenes. A total of seven controlled trials satisfied the inclusion criteria for the meta-analysis. The pooled mean difference of thigh circumference reduction between the treated and the controlled group was -0.46 cm (95% confidence intervals, CI: -0.85, -0.08), with significant heterogeneity between studies (P < 0.001). CONCLUSION: This article provides a systematic evaluation of the scientific evidence of the efficacy of cosmetic products in cellulite reduction and supports a moderate efficacy in thigh circumference reduction.

The role of Mediterranean diet on the risk of pancreatic cancer.

BACKGROUND: The Mediterranean diet has been shown to have a beneficial role on various neoplasms, but data are scanty on pancreatic cancer. METHODS: We analysed data from two case-control studies conducted in Italy between 1983 and 2008, including 362 and 326 pancreatic cancer cases and 1552 and 652 hospital-controls, respectively. A Mediterranean Diet Score (MDS) summarising major characteristics of the Mediterranean diet was used in the two studies separately and overall. Two further scores of adherence to the Mediterranean diet were applied in the second study only, the Mediterranean Dietary Pattern Adherence Index (MDP) and the Mediterranean Adequacy Index (MAI). RESULTS: Odds ratios (ORs) for increasing levels of the scores (i.e., increasing adherence) were estimated using multiple logistic regression models. Odds ratio for a MDS score ≥6 compared with <3 was 0.57 (95% confidence interval (CI) 0.34-0.95) in the first study, 0.51 (95% CI 0.29-0.92) in the second study, and 0.48 (95% CI 0.35-0.67) overall. A trend of decreasing risk was observed also for the MDP and MAI the ORs for the highest vs the lowest quintile being 0.44 (95% CI 0.27-0.73) for MDP and 0.68 (95% CI 0.42-1.11) for the MAI. The results were consistent across strata of age, sex, education, body mass index, alcohol drinking, tobacco smoking, and diabetes. CONCLUSION: Our study provides evidence that a priori-defined scores measuring adherence to the Mediterranean diet are favourably associated with pancreatic cancer risk.

Proanthocyanidins and other flavonoids in relation to endometrial cancer risk: a case-control study in Italy.

BACKGROUND: Because of their antioxidant and antimutagenic properties, flavonoids may reduce cancer risk. Some flavonoids have antiestrogenic effects that can inhibit the growth and proliferation of endometrial cancer cells. METHODS: In order to examine the relation between dietary flavonoids and endometrial cancer, we analysed data from an Italian case-control study including 454 incident, histologically confirmed endometrial cancers and 908 hospital-based controls. Information was collected through a validated food-frequency questionnaire. We applied data on food and beverage composition to estimate the intake of flavanols, flavanones, flavonols, anthocyanidins, flavones, isoflavones, and proanthocyanidins. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from multiple logistic regression models conditioned on age and study centre and adjusted for major confounding factors. RESULTS: Women in the highest quartile category of proanthocyanidins with ≥3 mers vs the first three quartile categories had an OR for endometrial cancer of 0.66 (95% CI=0.48-0.89). For no other class of flavonoids, a significant overall association was found. There was a suggestion of an inverse association for flavanones and isoflavones among women with body mass index <25 kg m(-2), and, for flavanones, among parous or non-users of hormone-replacement therapy women. CONCLUSION: High consumption of selected proanthocyanidins may reduce endometrial cancer risk.

Family history of cancer and the risk of cancer: a network of case-control studies.

BACKGROUND: The risk of many cancers is higher in subjects with a family history (FH) of cancer at a concordant site. However, few studies investigated FH of cancer at discordant sites. PATIENTS AND METHODS: This study is based on a network of Italian and Swiss case-control studies on 13 cancer sites conducted between 1991 and 2009, and including more than 12 000 cases and 11 000 controls. We collected information on history of any cancer in first degree relatives, and age at diagnosis. Odds ratios (ORs) for FH were calculated by multiple logistic regression models, adjusted for major confounding factors. RESULTS: All sites showed an excess risk in relation to FH of cancer at the same site. Increased risks were also found for oral and pharyngeal cancer and FH of laryngeal cancer (OR = 3.3), esophageal cancer and FH of oral and pharyngeal cancer (OR = 4.1), breast cancer and FH of colorectal cancer (OR = 1.5) and of hemolymphopoietic cancers (OR = 1.7), ovarian cancer and FH of breast cancer (OR = 2.3), and prostate cancer and FH of bladder cancer (OR = 3.4). For most cancer sites, the association with FH was stronger when the proband was affected at age <60 years. CONCLUSIONS: Our results point to several potential cancer syndromes that appear among close relatives and may indicate the presence of genetic factors influencing multiple cancer sites.

Dietary patterns and gastric cancer risk: a systematic review and meta-analysis.

BACKGROUND: Declines in gastric cancer (GC) incidence and mortality have been related to improvements in diet. It is therefore important to consider dietary patterns. DESIGN: We conducted a systematic review and meta-analysis of the literature through Medline and Embase databases. RESULTS: We identified 16 papers, of these 9 derived dietary patterns through an a posteriori method, 5 through a priori scores, and 2 used both approaches. Eight studies that used the a posteriori approach were considered for the meta-analysis. A favorable role on GC emerged for the 'Prudent/healthy', with an odds ratio (OR) of 0.75 [95% confidence interval (CI): 0.63-0.90], for the highest versus the lowest category. Similar results emerged for separate anatomical subtypes. An unfavorable role on GC emerged for the 'Western/unhealthy' dietary pattern, with an OR of 1.51 (95% CI: 1.21-1.89). This association was weaker for the distal/NOS (not otherwise specified) category (OR = 1.36) compared with the cardia GC (OR = 2.05). Among the a priori scores, the ORs ranged from 0.2 to 0.7 for the favorable and from 1.8 to 6.9 for the unfavorable ones. CONCLUSION: There is a ~2-fold difference in GC risk between a 'Prudent/healthy' diet-rich in fruits and vegetables, and a 'Western/unhealthy' diet-rich in starchy foods, meat and fats.

Dietary patterns and upper aerodigestive tract cancers: an overview and review.

BACKGROUND: The relationship between diet and cancers of the upper aerodigestive tract (UADT) has been investigated through dietary patterns. DESIGN: Published studies on the relationship between a priori and a posteriori dietary patterns and UADT cancers were selected through a Medline search. RESULTS: Twenty-four case-control studies were identified. Most of them identified a posteriori dietary patterns, mainly using principal component factor analysis, and a few used a priori dietary patterns, based on the available evidence on known effects of dietary habits on UADT cancers. In one study, no association was found between the identified patterns and UADT cancers. All the remaining 23 papers reported at least one favorable or unfavorable dietary pattern related to UADT cancers. The most consistent findings are the beneficial role of a dietary pattern based on fruit and vegetables or nutrients mostly contained in such foods, and the unfavorable role of an alcohol drinker pattern. A possible unfavorable role of patterns based on meats and animal products emerged as well. CONCLUSION: The consistency of results among populations indicates that diets rich in fruit and vegetables, and poor in alcohol and animal products are favorable for UADT cancers.

Adherence to the European food safety authority's dietary recommendations and colorectal cancer risk.

BACKGROUND/OBJECTIVE: The European Food Safety Authority (EFSA) recently published dietary guidelines for the intakes of carbohydrates, fiber, fats and water. We evaluated their role on the risk of a specific disease, known to be related to diet. SUBJECTS/METHODS: We used data from an Italian case-control study including 1953 colorectal cancer (CRC) cases and 4154 controls. We developed a so-called EFSA index summing up 1 point for adherence to each EFSA guideline. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of CRC and its subsites were derived from unconditional multiple logistic regression models, for both the index and its components. RESULTS: When each EFSA index component was analyzed separately, we found significant increased risks of CRC for non adherence to the guidelines on linoleic (OR=1.20, 95% CI, 1.07-1.36) and alpha-linolenic fatty acids (OR=1.19, 95% CI, 1.06-1.34). When all the guidelines were included in the same model, no significant association emerged. Compared with minimal adherence, the ORs of CRC for subsequent EFSA index scores were 1.03 (95% CI, 0.72-1.47), 1.05 (95% CI, 0.75-1.48), 1.04 (95% CI, 0.81-1.60), 0.99 (95% CI, 0.69-1.43), and 1.04 (95% CI, 0.67-1.61). No significant association emerged for colon and rectal cancer separately, and for males and females. CONCLUSIONS: Overall adherence to the EFSA dietary guidelines is not associated to colorectal, colon and rectal cancer risk in our population. Adherence to guidelines on linoleic and alpha-linolenic fatty acids may have a modest beneficial role on CRC risk.

Dietary patterns and the risk of esophageal cancer.

BACKGROUND: The role of dietary habits on esophageal cancer risk has been rarely considered in terms of dietary patterns. PATIENTS AND METHODS: We analyzed data from an Italian case-control study, including 304 cases with squamous cell carcinoma of the esophagus and 743 hospital controls. Dietary habits were evaluated using a food frequency questionnaire. A posteriori dietary patterns were identified through principal component factor analysis performed on 28 selected nutrients. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained from multiple logistic regression models applied on quartiles of factor scores, adjusting for potential confounding variables. RESULTS: We identified five major dietary patterns, named 'animal products and related components', 'vitamins and fiber', 'starch-rich', 'other polyunsaturated fatty acids and vitamin D', and 'other fats'. The 'animal products and related components' pattern was positively related to esophageal cancer (OR = 1.64, 95% CI:1.06-2.55, for the highest versus the lowest quartile of factor scores category). The 'vitamins and fiber' (OR = 0.50, 95% CI: 0.32-0.78) and the 'other polyunsaturated fatty acids and vitamin D' (OR = 0.48, 95% CI: 0.31-0.74) were inversely related to esophageal cancer. No significant association was observed for the other patterns. CONCLUSION: Our findings suggest that a diet rich in foods from animal origin and poor in foods containing vitamins and fiber increase esophageal cancer risk.

A meta-analysis of coffee consumption and pancreatic cancer.

BACKGROUND: Since when in 1981 a case-control study showed a positive association between coffee and pancreatic cancer, several studies reported inconsistent results on this issue. MATERIALS AND METHODS: We conducted a systematic bibliography search updated March 2011 to identify observational studies providing quantitative estimates for pancreatic cancer risk in relation to coffee consumption. We used a meta-analytic approach to estimate overall relative risk (RR) and 95% confidence interval (CI) for the highest versus the lowest coffee consumption categories, using random-effects models. RESULTS: Based on 37 case-control and 17 cohort studies (10,594 cases), the pooled RR for the highest versus lowest intake was 1.13 (95% CI 0.99-1.29). Considering only the smoking-adjusting studies, the pooled RRs were 1.10 (95% CI 0.92-1.31) for the 22 case-control, 1.04 (95% CI 0.80-1.36) for the 15 cohort, and 1.08 (95% CI 0.94-1.25) for all studies. The pooled RR for the increment of one cup of coffee per day was 1.03 (95% CI 0.99-1.06) for the 28 smoking-adjusting studies reporting three or more coffee consumption categories. No significant heterogeneity was observed across strata of study design, sex, geographic region, and other selected characteristics. CONCLUSIONS: This meta-analysis provides quantitative evidence that coffee consumption is not appreciably related to pancreatic cancer risk, even at high intakes.

Anthropometric measures at different ages and endometrial cancer risk.

BACKGROUND: Endometrial cancer is strongly associated with body mass index (BMI), but the influence of BMI history and of different types of obesity is uncertain. METHODS: A case-control study was carried out in Italy including 454 cases and 908 controls admitted to hospital for acute non-hormone-related conditions. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using multivariate logistic and spline regression models. RESULTS: The OR for BMI >30 at diagnosis compared with 20 to <25 kg m(-2) was 4.08 (95% CI: 2.90-5.74). The association for BMI was monotonic with a possible steeper increase for BMI above 28. Conversely, waist-to-hip ratio (WHR) showed a bell shaped curve with increased OR (2.10; 95% CI: 1.43-3.09) in the intermediate tertile only. After stratification by BMI at diagnosis, history of weight loss and BMI at age 30 did not influence endometrial cancer risk. History of obesity in middle age had a weak and not significant adverse effect among obese women (OR=1.60; 95% CI: 0.52-4.96). CONCLUSION: The predominant importance of recent weight compared to lifetime history, justifies encouraging weight reduction in women at any age.

Clustering dietary habits and the risk of breast and ovarian cancers.

BACKGROUND: Limited information is available on the relationship between dietary patterns and breast and ovarian cancers. PATIENTS AND METHODS: Cases were 2569 breast cancers and 1031 ovarian cancers hospitalized in four Italian areas from 1991 to 1999. Controls were 3413 women in hospital for acute non-neoplastic diseases. Dietary habits were investigated through a validated food-frequency questionnaire. Dietary patterns were obtained from a K-means clustering on factor scores from factor analysis. Odds ratios (ORs) for both cancers were estimated using unconditional multiple logistic regression models on clusters of patients. Floating absolute risk method was used for reporting 95% floating confidence intervals (FCIs). RESULTS: We identified five groups of subjects. The G3 cluster, including subjects with the lowest intakes of any food group, was used as reference. The G5 cluster, including subjects mainly consuming bread and pasta, was unfavorable for both cancers (OR=1.23, 95% FCI=1.08-1.38 for breast cancer, OR=1.21, 95% FCI=1.03-1.42 for ovarian cancer). The G1 group, including subjects mainly consuming fruits and vegetables, was protective against ovarian cancer (OR=0.81, 95% FCI=0.67-0.98). CONCLUSIONS: A diet mainly based on bread and pasta is unfavorable for breast and ovarian cancers; a diet rich in fruits and vegetables may be associated with a reduced risk of ovarian cancer.

Laccase isoforms with unusual properties from the basidiomycete Steccherinum ochraceum strain 1833.

AIMS: To isolate and characterize the laccase isoforms from S. ochraceum 1833 - a new active producer of high extracellular laccase activity. METHODS AND RESULTS: Three laccase isoforms (laccases I, II and III) with 57.5, 59.5 and 63 kDa molecular masses respectively were purified from S. ochraceum 1833 and in contrast to the known laccases had strongly pronounced absorption at 611 nm with molar extinction coefficients ranging from 7170 to 7830 mol(-1) l cm(-1). All isoforms showed maximal activity with ABTS at low pH (

Glycemic index, glycemic load and thyroid cancer risk.

BACKGROUND: Risk of thyroid cancer has already been related to refined cereals and starch food, but the association has not been studied in terms of glycemic index (GI) and glycemic load (GL). PATIENTS AND METHODS: We analyzed data from a case-control study conducted in Italy from 1986 to 1992 and including 399 histologically confirmed and incident cases of thyroid cancer and 616 control subjects. Information on dietary habits was derived through a food-frequency questionnaire and multivariate odds ratios (ORs) for GI and GL levels were estimated with adjustment for age, education, sex, area of residence, history of diabetes, body mass index, smoking, alcohol consumption, intake of fruit and vegetables, and noncarbohydrate energy intake. RESULTS: Compared with the lowest tertile, the ORs in subsequent tertiles were 1.68 and 1.73 for GI, and 1.76 and 2.17 for GL. The OR for highest tertile of GI compared with lowest one was 1.70 for papillary and 1.57 for follicular thyroid cancer. The ORs for GL were 2.17 for papillary and 3.33 for follicular thyroid cancer. CONCLUSION: Our study shows that high dietary levels of GI and GL are associated with thyroid cancer risk.

Preliminary crystallographic analysis of salicylate 1,2-dioxygenase from Pseudaminobacter salicylatoxidans.

Salicylate 1,2-dioxygenase, a new ring-fission dioxygenase from the naphthalenesulfonate-degrading strain Pseudaminobacter salicylatoxidans which oxidizes salicylate to 2-oxohepta-3,5-dienedioic acid by a novel ring-fission mechanism, has been crystallized. Diffraction-quality crystals of salicylate 1,2-dioxygenase were obtained using the sitting-drop vapour-diffusion method at 277 K from a solution containing 10%(w/v) ethanol, 6%(w/v) PEG 400, 0.1 M sodium acetate pH 4.6. Crystals belong to the primitive tetragonal space group P4(3)2(1)2 or P4(1)2(1)2, with unit-cell parameters a = 133.3, c = 191.51 A. A complete data set at 100 K extending to a maximum resolution of 2.9 A was collected at a wavelength of 0.8423 A. Molecular replacement using the coordinates of known extradiol dioxygenases structures as a model has so far failed to provide a solution for salicylate 1,2-dioxygenase. Attempts are currently being made to solve the structure of the enzyme by MAD experiments using the anomalous signal of the catalytic Fe(II) ions. The salicylate 1,2-dioxygenase structural model will assist in the elucidation of the catalytic mechanism of this ring-fission dioxygenase from P. salicylatoxidans, which differs markedly from the known gentisate 1,2-dioxygenases or 1-hydroxy-2-naphthoate dioxygenases because of its unique ability to oxidatively cleave salicylate, gentisate and 1-hydroxy-2-naphthoate with high catalytic efficiency.

Resveratrol and breast cancer risk.

Resveratrol is a non-flavonoid polyphenol that has attracted attention as a potential anticancer agent in vitro and in vivo, but scanty epidemiological data are available. We have therefore analysed the relation between dietary intake of resveratrol and breast cancer risk using data from a case-control study conducted between 1993 and 2003 in the Swiss Canton of Vaud on 369 cases and 602 controls. Compared with the lowest tertile of total resveratrol intake, the multivariate odds ratios (OR) were 0.50 for the intermediate and 0.39 for the highest tertile, and the trend in risk was significant. A significant inverse association was observed for resveratrol from grapes (OR = 0.64 and 0.55), but not for wine. The inverse relation between resveratrol and breast cancer risk was not explained by several potential confounding factors, including detailed allowance for alcohol intake, nor attributable to a non-specific favourable effect of fruit on breast cancer risk.

Reproducibility and validity of coffee and tea consumption in Italy.

OBJECTIVE: The reproducibility and validity of coffee, decaffeinated coffee and tea intake has not been adequately studied, particularly in Italy, where coffee drinking is peculiar in terms of type and amount of coffee consumed. DESIGN: We compared coffee and tea consumption, measured by two interviewer-administered food frequency questionnaires (FFQ), with average intake derived from two 7-day dietary (DD) records (the reference method) on 395 volunteers. The Pearson correlation coefficients (r) were used to assess both reproducibility and validity of information on coffee intake. RESULTS: A satisfactory level of reproducibility and validity of the pattern consumption was observed for coffee, decaffeinated coffee and tea. The reproducibility for both sex combined showed r of 0.74-0.78 for coffee, 0.57-0.65 for decaffeinated coffee and 0.61-0.67 for tea. The validity was about 0.70 for coffee, around 0.58 for decaffeinated coffee and 0.56-0.60 for tea intake. CONCLUSIONS: The FFQ is a satisfactorily reliable and valid instrument for collecting information on coffee, decaffeinated coffee and tea intake.