Dietary lignan and proanthocyanidin consumption and colorectal adenoma recurrence in the Polyp Prevention Trial

Lignans and proanthocyanidins are plant polyphenols that have shown protective properties against colorectal neoplasms in some human studies. Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to prospectively evaluate the association between lignan and proanthocyanidin intake, estimated from databases linked to a food frequency questionnaire, and adenoma recurrence in 1,859 participants of the Polyp Prevention Trial. Overall, individual or total lignans or proanthocyanidins were not associated with colorectal adenoma recurrence. However, in sex-specific analyses, total lignan intake was positively associated with any adenoma recurrence in women (highest vs. lowest lignan intake quartile OR = 2.07, 95% CI: 1.223.52, p trend = 0.004) but not in men (p interaction = 0.04). To conclude, dietary lignan and proanthocyanidin consumption were not generally related to colorectal adenoma recurrence; however, high lignan intake may increase the risk of adenoma recurrence in women.This is the publisher’s final pdf. The published article is copyrighted by Wiley and can be found at: http://onlinelibrary.wiley.com/.Keywords: Proanthocyanidins, Lignans, Cancer prevention, Colorectal cancer, Colorectal adenom

Dietary cooked navy beans and their fractions attenuate colon carcinogenesis in azoxymethane-induced ob/ob mice

Based on the protective effects of cooked dry bean consumption in a human intervention study, we evaluated which fraction of cooked dry beans is responsible for its cancer-preventive effects. Cooked navy beans (whole beans), the insoluble fraction (bean residue) or soluble fraction of the 60% (vol:vol) ethanol extract of cooked navy beans (bean extract), or a modified AIN-93G diet (16.6% fat including 12.9% lard) as control diet were fed to 160 male obese ob/ob mice after 2 azoxymethane injections. In comparison to control-fed mice, dysplasia, adenomas, or adenocarcinomas were detected in fewer mice on either bean fraction diet (percent reduction from control: whole beans 54%, P = 0.10; bean residue 81%, P = 0.003 ; bean extract 91%, P = 0.007) , and any type of colon lesions, including focal hyperplasia, were found in fewer mice on each of the 3 bean diets percent reduction from control: whole bean 56%, P= 0.04; bean residue 67%, P = 0.01; bean extract 87%, 373 374 G. BOBE ET AL. P = 0.0003. These results suggest that both the soluble and the insoluble fraction of the extract contribute to the cancer-protective effect of cooked navy beans. INTRODUCTION Colorectal cancer (CRC) is the third most commonly diagnosed type of cancer and the fourth most common cause of cancer-related death worldwide (1). In the United States, CRC is the fourth leading cancer in incidence rates and the second leading cause of cancer-related mortality with a 5-yr survival rate of 64% (2). Despite the effectiveness of screening (3,4), there is limited impact for CRC prevention because of low screening rates (5). Nutrition remains critical for CRC prevention. It is estimated that nutrition could prevent 70-80% of all CRC cases (6). This is important, as the annual CRC treatment costs in the United States are estimated to be $6.5 billion (7). Two of the main risk factors for CRC, which are both diet related, are obesity and inflammation (8). Thus, ob/ob mice might provide a suitable animal model to study the link between diet and CRC because they have a mutation in the leptin gene, which results in hyperphagia, obesity, hyperinsulinemia, hyperglycemia, and increased inflammatory response to liposaccharides (9). Dry beans (Phaseolus vulgaris L.), which belong to the Leguminosae family, are a dietary staple in many Latin American, Eastern, and South African countries that potentially could prevent CRC (10,11). Ecological analysis indicates a decreased risk of death associated with colon cancer in countries with higher consumption of beans (12). In studies that have examined the association between colon cancer and individual intakes of legumes, the results indicate a protective effect in populations with higher legume consumption (13-18). In the only study that examined the effect of dry bean consumption separately, male participants, who consumed at least 31 g of cooked dry beans daily, had reduced risk of advanced adenomatous polyp recurrence in a 4-yr nutrition intervention study (Polyp Prevention Trial (19); unpublished data). In animal models, dry beans commonly consumed in the United States, such as pinto, black, and navy beans, reduced azoxymethane(AOM)-induced colon adenocarcinomas in F344 rat

Identification and monitoring of metabolite markers of dry bean consumption in parallel human and mouse studies

SCOPE: Aim of the study was to identify and monitor metabolite markers of dry bean consumption in parallel human and mouse studies that each had shown chemopreventive effects of dry bean consumption on colorectal neoplasia risk. METHODS and RESULTS: Using LC/mass spectroscopy ± ESI and GC/mass spectroscopy, serum metabolites of dry beans were measured in 46 men before and after a 4-week dry bean enriched diet (250 g/day) and 12 mice that received a standardized diet containing either 0 or 10% navy bean ethanol extract for 6 weeks; we also investigated fecal metabolites in the mice. The serum metabolites identified in these controlled feeding studies were then investigated in 212 polyp-free participants from the Polyp Prevention Trial who self-reported either increased (≥+31 g/day from baseline), high dry bean intake of ≥42 g/day in year 3 or low, unchanged dry bean consumption of <8 g/day; serum was analyzed from baseline and year 3. Serum pipecolic acid and S-methyl cysteine were elevated after dry bean consumption in human and mouse studies and reflected dry bean consumption in the Polyp Prevention Trial. CONCLUSION: Serum levels of pipecolic acid and S-methyl cysteine are useful biomarkers of dry bean consumption.Keywords: Pipecolic acid, Dry bean consumption, Metabolomics, S-methyl cysteine, Biomarker

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure