Promotion of the mediterranean diet incancer long-survivors by means of the Med-Food Anticancer Program: a pilot study.

BACKGROUND: The intervention "Med-Anticancer Food Program" has proven to be effective in promoting the Mediterranean Diet, significantly increasing the Mediterranean Adequacy Index in healthy subjects. There are no studies that have investigated the effectiveness of this intervention in individuals who have had a diagnosis of cancer. OBJECTIVE: To perform a pilot study to assess the opportunity of employing the methodology of the Med-Anticancer Food Program in order to encourage "long-term cancer survivors" to adhere to the Mediterranean Diet, as well as healthy people, and this in order to apply the program to larger groups. METHODS: From the residents' register of Foggia, a city in southern Italy, forty adults of both sexes, over 25 years of age, were recruited at random and assigned (1:1) as follows: - Twenty healthy subjects to the intervention-1 group - Twenty long-term cancer survivors to the intervention-2 group. The Med-Anticancer Food Program was applied to both groups with an articulated intervention 11 weeks long, followed by a 52-week period of follow up. By means of a food diary of the last 3 days, the Mediterranean Adequacy Index values were calculated before intervention (T0), after a period of 11 weeks of interventions (T1) and at the end of the 52 weeks of follow-up period (T2). The H0 hypothesis of the study was that there are no differences between the two interventions in reaching by T1, and maintaining at T2, values of Mediterranean Adequacy Index around 7, considered the optimum for adherence to the Mediterranean diet. RESULTS: Out of the subjects assigned to the intervention-1 group (n = 20), 11 subjects have completed the 52-months follow-up (55.0% ); for intervention-2, 16 (80%) out of 20 have completed it. The average age of subjects was 52.1 years. The Mediterranean Adequacy Index, of intervention-1 group significantly increased from 2.8 (T0) to 9.2 (T1) and to 9.0 (T2) (p <0.0001); whereas, in the intervention-2 group, Mediterranean Adequacy Index moved from 2.4 (T0) to 10.2 (T1) and to 9.3 (T2) (p <0.0001). The difference of Mediterranean Adequacy Index between the two study groups at T1 and T2 was not significant. Such non-significance persists also after the stratification by sex and age obtained with Mantel-Haenszel procedure. The performance of the values of the laboratory parameters considered (folic acid, total cholesterol, alkyl resorcinol) was similar in the subjects of both intervention 1 and 2, without any difference, while considered at a basal level T0, at T1 and at the end of the follow-up period (T2). CONCLUSIONS: The results of our work suggest the feasibility of conducting the Med-Anticancer Food Program in long-term cancer survivors. The results of the pilot study show that such intervention, carried on a small number of long term cancer survivors, is adequate to assess its feasibility but, due to the limited size of our study, a confirmation is required through larger nutritional prevention intervention studies.

Dopamine transporter (DAT1/SLC6A3) polymorphism and the association between being born small for gestational age and symptoms of ADHD.

Being small for gestational age (SGA) has been established as a risk factor for Attention Deficit Hyperactivity Disorder (ADHD). Likewise, several molecular genetic studies have found a link between DAT1 and ADHD. This study investigated whether SGA moderates the effect of dopamine transporter gene variants on the risk of ADHD. A total of 546 children of European descent were genotyped at age 11 for seven DAT1 SNPs (rs6347, rs11564774, rs40184, rs1042098, rs2702, rs8179029 and rs3863145). The Strengths and Difficulties Questionnaire was used to measure symptoms of ADHD at ages 3.5, 7 and 11. We found significant gene-environment interactions between birth weight and DAT1 SNPs (rs6347, rs40184, rs1042098, rs3863145) on ADHD symptoms at 3.5 years only. Results suggest that genotypic variation of DAT1 may confer a relative protective effect against ADHD in SGA individuals. This study supports the idea that being born SGA moderates the effect of the DAT1 gene on ADHD symptoms in the preschool years and may help to explain some of the heterogeneity in ADHD outcomes.

A quinazoline-based HDAC inhibitor affects gene expression pathways involved in cholesterol biosynthesis and mevalonate in prostate cancer cells.

Chronic inflammation can lead to the development of cancers and resolution of inflammation is an ongoing challenge. Inflammation can result from dysregulation of the epigenome and a number of compounds that modify the epigenome are in clinical use. In this study the anti-inflammatory and anti-cancer effects of a quinazoline epigenetic-modulator compound were determined in prostate cancer cell lines using a non-hypothesis driven transcriptomics strategy utilising the Affymetrix PrimeView® Human Gene Expression microarray. GATHER and IPA software were used to analyse the data and to provide information on significantly modified biological processes, pathways and networks. A number of genes were differentially expressed in both PC3 and DU145 prostate cancer cell lines. The top canonical pathways that frequently arose across both cell lines at a number of time points included cholesterol biosynthesis and metabolism, and the mevalonate pathway. Targeting of sterol and mevalonate pathways may be a powerful anticancer approach.

Differential modification of genetic susceptibility to childhood eczema by two probiotics.

BACKGROUND: In a double-blind, randomized, placebo-controlled birth cohort, we have recently shown a beneficial effect of Lactobacillus rhamnosus HN001 (HN001) for the prevention of eczema in children through to 6 years of age but no effect of Bifidobacterium animalis subsp lactis HN019 (HN019). OBJECTIVE: Among this cohort of children, we aim to investigate whether these probiotics could modify the expression of genetic predisposition to eczema conferred by genetic variation in susceptibility genes. METHODS: Thirty-three eczema susceptibility SNPs (in eleven genes) were genotyped in 331 children of European ancestry. RESULTS: Children who carried a genetic variant that put them at a high risk of developing eczema were less likely to develop eczema if they had been randomized to the HN001 intervention group compared to those in the placebo group. HN019 was also able to protect against the effects of some SNPs. As well as modifying genetic susceptibility to childhood eczema, HN001 was also found to modify genetic susceptibility to eczema severity and atopy risk. CONCLUSION AND CLINICAL RELEVANCE: This is the first study to show an effect of a probiotic on reducing eczema risk amongst those with particular eczema-associated genotypes. Our findings suggest that Lactobacillus rhamnosus HN001 may be particularly effective in preventing eczema in children with specific high-risk genotypes.

Training the teachers for improving primary schoolchildren's fruit and vegetables intake: a randomized controlled trial.

Effectiveness comparison of different school-based nutrition education interventions to improve fruit and vegetable (F&V) consumption in schoolchildren not yet well researched. We evaluated the effectiveness of two school-based interventions promoting fruit and vegetable intake among Italian schoolchildren. In this randomized intervention trials, the first intervention was conducted by schoolteachers who attended a nutritionist-led training course (group-1), the second intervention conducted by schoolteachers who performed a self-training course (group-2). Thirty-two second to fifth-grade elementary classes enrolling 96 schoolteachers and 813 schoolchildren were randomized, and assigned to the two different nutrition education interventions. 804 students completed the study. By the end of the study, the group-1 (n = 409) followed by the teachers who attended a nutritionist-led course successfully increased the consumption of fruit and vegetables: in 183 (44.7%) and 157 (38.3%) schoolchildren respectively; the group-2 (n = 395) with teachers who performed a self-training course reported an increased consumption of fruit and vegetables in 81 (20.5%) and 76 (19.2%), respectively. This study indicates that a school-based nutrition education conducted by teachers who attended a nutritionist-led training course has a significant impact on primary school-age children's F&V intake.

Randomized, controlled nutrition education trial promotes a Mediterranean diet and improves anthropometric, dietary, and metabolic parameters in adults.

Several studies have shown that uptake of a Mediterranean diet could prevent many chronic diseases, such as cancer. However, the effectiveness of Mediterranean diet promotion interventions has not been well researched. The aim of this study was to evaluate the effectiveness of a nutrition education intervention for promoting the Mediterranean diet, by assessing changes in anthropometric, physical activity, dietetic and metabolic parameters in healthy adult subjects, before and after the intervention. Eighty participants, both sexes, aged 51-59 years, were randomly assigned in a 1:1 ratio to the intervention or the control group. The intervention group participated in the Med-Food Anticancer Program (MFAP), designed to promote a Mediterranean diet. This was organized into 15 weeks of intensive training and 10 weeks of consolidation. Participants of the two groups were assessed at baseline (T0) and after 25 weeks (T1) for anthropometric, physical activity, dietetic, and metabolic parameters. The hypothesis was that subjects participating in MFAP would show an improvement in these parameters. The primary endpoint was an improvement of the Mediterranean Adequacy Index (MAI), calculated by dividing the percentage of total energy from typical Mediterranean food groups by the percentage of total energy from non-typical Mediterranean food groups. At T1, the intervention group showed a significant decrease in body weight (-8.3%, P = 0.045), body mass index (-12.4%, P = 0.05), cheese (53.0%, P < 0.0001) and meat (-49.3%, P = 0.005) intake, fasting glycaemia (-9.2%, P = 0.012), and fasting insulin (-32.6%, P = 0.014), C-Reactive Protein (-34.0%, P = 0.005). They showed a significant increase in MAI (+213, P < 0.0001), physical activity (expressed in steps per day, +200.4%, P < 0.0001), fruit (+38.8, P < 0.0001), vegetables (29.3%, P < 0.0001), and dietary fiber (+38.6%, P = 0.04) intake. In contrast, the control group presented non-significant variations in measured parameters, for exception of cheese intake (+18.2%, P < 0.0001). The MFAP was found to promote uptake of the Mediterranean diet, and improve anthropometric, physical activity, dietary, and metabolic parameters in healthy subjects.

[Nutrition prevention intervention for cancers: "Med-Food Anticancer Program"]. / L'intervento di prevenzione nutrizionale dei tumori: "Med-Food Anticancer Program".

Several studies recommend the Mediterranean diet and daily physical activity to prevent cancer development. These recommendations, however must be transformed into public health structured programmes, so that they assume operational effectiveness. The aim of the diet and lifestyle intervention called Med-Food Anticancer Program (MFAP) is to promote the Mediterranean diet and physical activity in the adult population. In particular; the target for participants in the intervention is the increased consumption of legumes, fish, whole grain bread and cereals, fruits and vegetables, and the decreased consumption of meat, cheese and foods of animal origin. At the same time, it is recommended to make at least ten thousand steps a day. Two studies have shown the effectiveness of MFAP.

PTPN2 but not PTPN22 is associated with Crohn's disease in a New Zealand population.

Recent genome-wide association studies have provided evidence for the involvement of the genes PTPN2 and PTPN22 in the pathogenesis of Crohn's disease (CD). We investigated whether genetic variants in these genes were associated with CD in a New Zealand population. Single-nucleotide polymorphisms (SNPs) rs2542151 (PTPN2) and rs2476601 (PTPN22) were genotyped in 315 CD cases and 481 controls. In this sample, we were able to confirm an association between CD and PTPN2 (genotypic P = 0.019 and allelic P = 0.011), and phenotypic analysis showed an association of this SNP with late age at first diagnosis, inflammatory and penetrating CD behaviour, requirement of bowel resection and being a smoker at diagnosis. There was no evidence for an association with PTPN22.

15-week long school-based nutritional education program to promote Italian primary schoolchildren's fruit and vegetable intake.

A short-version (15-week long) of school-based nutrition education program called "Bring Fruit to School" to enhance primary schoolchildren's fruit and vegetable (F&V) intake was evaluated. We recruited 199 primary schoolchildren from 8 classes (grade 2-5). The primary end-point was an increase in the children's F&V intake. The intervention period lasted 15 weeks, and was divided into three phases: weeks 1-5, weeks 6-10 and weeks 11-15. The F&V intake of the schoolchildren was also monitored in a subsequent follow-up period (16th-32nd week). By week 15, 92 (46.2%, P < .001) schoolchildren increase fruit intake and 91 (45.7%, P < .001) increase vegetable intake. The F&V intake increased during the intervention period and was constant in follow-up. The BFtS program is an effective means to promote primary schoolchildren's F&V intake, and was implemented in Italy by the Food and Nutrition Service of Foggia's Local Health Authority. It could be extended to many other countries by local nutrition agencies, such as associations for nutrition.

Single nucleotide polymorphisms in human Paneth cell defensin A5 may confer susceptibility to inflammatory bowel disease in a New Zealand Caucasian population.

BACKGROUND: Human Paneth cell alpha-defensins, especially DEFA5, are involved in maintaining homeostasis of the human microbial microflora. Since breakdown of normal mucosal antibacterial defence occurs in inflammatory bowel disease (IBD), variants in the DEFA5 gene could be associated with IBD risk. SUBJECTS: A cohort of 25 patients with indeterminate colitis (IC), 405 with ulcerative colitis (UC), and 385 with Crohn's disease (CD), were compared with 201 control individuals from the Canterbury region in New Zealand. METHODS: A 15 kb haplotype block surrounding DEFA5 contained 35 HapMap markers which were polymorphic in Caucasians. Four markers (A-D) were selected to tag 27 of the 35 markers at r(2)>0.68, and were genotyped in DNA samples. RESULTS: Minor allele frequencies for all single nucleotide polymorphisms (SNPs) were somewhat elevated in patients. Subgroup analysis showed SNP A had odds ratio 1.44 in UC patients with pancolitis (95% C.I. 1.07-1.94), SNP B odds ratio 2.37 in CD patients with onset prior to 17 years age (95% C.I. 1.12-5.03), SNP C odds ratio 1.68 in UC patients with left colonic localisation (95% C.I. 1.12-2.52), and SNP D had odds ratio 1.56 in CD patients with one or more relatives with IBD (95% C.I. 1.03-2.35). Two two-marker haplotypes and one three-marker haplotype were associated with UC (p-values 0.025-0.05). CONCLUSIONS: The SNPs genotyped in our study were surrogates for common variants, and observed associations between these and IBD status are likely due to linkage disequilibrium with a functional common DEFA5 variant. Identifying such functional variants will be prioritized in subsequent work.

Gender-stratified analysis of DLG5 R30Q in 4707 patients with Crohn disease and 4973 controls from 12 Caucasian cohorts.

BACKGROUND: DLG5 p.R30Q has been reported to be associated with Crohn disease (CD), but this association has not been replicated in most studies. A recent analysis of gender-stratified data from two case-control studies and two population cohorts found an association of DLG5 30Q with increased risk of CD in men but not in women and found differences between 30Q population frequencies for males and females. Male-female differences in population allele frequencies and male-specific risk could explain the difficulty in replicating the association with CD. METHODS: DLG5 R30Q genotype data were collected for patients with CD and controls from 11 studies that did not include gender-stratified allele counts in their published reports and tested for male-female frequency differences in controls and for case-control frequency differences in men and in women. RESULTS: The data showed no male-female allele frequency differences in controls. An exact conditional test gave marginal evidence that 30Q is associated with decreased risk of CD in women (p = 0.049, OR = 0.87, 95% CI 0.77 to 1.00). There was also a trend towards reduced 30Q frequencies in male patients with CD compared with male controls, but this was not significant at the 0.05 level (p = 0.058, OR = 0.87, 95% CI 0.74 to 1.01). When data from this study were combined with previously published, gender-stratified data, the 30Q allele was found to be associated with decreased risk of CD in women (p = 0.010, OR = 0.86, 95% CI 0.76 to 0.97), but not in men. CONCLUSION: DLG5 30Q is associated with a small reduction in risk of CD in women.

Nutrigenomics in the whole-genome scanning era: Crohn's disease as example.

Nutrigenomics has the potential to tailor diets to optimize health, based on knowledge of key genetic polymorphisms. Identification of candidate genes is often based on a priori knowledge of disease processes. However, genome-wide association methods are not only validating previously identified genes and polymorphisms, but also revealing new gene-disease associations not anticipated from prior knowledge. In Crohn's disease (CD), such studies not only confirm the importance of caspase-activated recruitment domain 15 and major histocompatibility complex II molecules, but also reveal strong associations with the proinflammatory cytokine interleukin-23 receptor and autophagy-related 16-like gene. Genes identified to date in CD can be linked into two interrelated pathways: receptor-mediated cytokine induction or autophagocytosis. New genomic technologies need to be matched with innovative methodologies to characterize the likely impact of foods and to take the field to another dimension of value for human diet development and optimized health.

Mechanisms by which resistant starches and non-starch polysaccharide sources affect the metabolism and disposition of the food carcinogen, 2-amino-3-methylimidazo[4,5-f]quinoline.

Although both non-starch polysaccharides (NSP) and resistant starches (RS) are included in current definitions of dietary fibre, our previous work has suggested fundamental differences in the way in which these two classes of material affect the disposition and absorption of a dietary carcinogen. The present studies explore whether different effects on carcinogen metabolism could play a role in the contrasting patterns seen previously. Groups of female Wistar rats were pre-fed for 4 weeks one of five types of defined diet (AIN-76). The control diet contained 35% maize starch and no dietary fibre. The RS-containing diets had all the maize starch substituted with either Hi-maize or potato starch. In the NSP-containing diets, 10% of the maize starch was substituted with dietary fibre in the form of either lignified plant cell walls (wheat straw) or soluble dietary fibre (apple pectin). Pre-fed rats were gavaged with the food carcinogen, [2-14C] 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and plasma and urinary metabolites characterized using HPLC at various time intervals after administration. After 4 h gavage, plasma from rats on both RS-containing diets contained significantly higher levels of intact IQ and lower levels of the major metabolites, IQ-5-O-glucuronide and IQ-5-sulfate, as compared with plasma from the negative control group at this time. In contrast, plasma from animals on the NSP-containing wheat straw diet (and to a lesser extent the apple pectin diet) showed significantly lower levels of intact IQ, and significantly higher levels of the two major metabolites, as compared with those from the control rats. These different metabolite profiles were also reflected in different urinary excretion profiles. Urine from rats pre-fed RS-containing diets revealed significantly slower metabolite excretion as compared with urine from rats that had been given the NSP-containing diets. Western blotting methodologies also profiled differences between the effects of these two types of dietary fibre in the expression of xenobiotic metabolizing enzymes. We conclude that changes in activity and expression of xenobiotic metabolising enzymes could play a role in the contrasting effects of these two types of dietary fibre on carcinogen uptake and disposition.

The 10 basic requirements for a scientific paper reporting antioxidant, antimutagenic or anticarcinogenic potential of test substances in in vitro experiments and animal studies in vivo.

There is increasing evidence that chemicals/test substances cannot only have adverse effects, but that there are many substances that can (also) have a beneficial effect on health. As this journal regularly publishes papers in this area and has every intention in continuing to do so in the near future, it has become essential that studies reported in this journal reflect an adequate level of scientific scrutiny. Therefore a set of essential characteristics of studies has been defined. These basic requirements are default properties rather than non-negotiables: deviations are possible and useful, provided they can be justified on scientific grounds. The 10 basic requirements for a scientific paper reporting antioxidant, antimutagenic or anticarcinogenic potential of test substances in in vitro experiments and animal studies in vivo concern the following areas: (1) Hypothesis-driven study design; (2) The nature of the test substance; (3) Valid and invalid test systems; (4) The selection of dose levels and gender; (5) Reversal of the effects induced by oxidants, carcinogens and mutagens; (6) Route of administration; (7) Number and validity of test variables; (8) Repeatability and reproducibility; (9) Statistics; and (10) Quality Assurance.

Evidence for epidermal growth factor receptor-enhanced chemosensitivity in combinations of cisplatin and the new irreversible tyrosine kinase inhibitor CI-1033.

Irreversible inhibitors of the epidermal growth factor receptor (EGFR) are showing promise in clinical trials. This report is the first to show that inhibition of the EGFR tyrosine kinase by an irreversible binder synergizes with cisplatin, at least in EGFR-overexpressing tissue culture cell lines in vitro. Unlike previous synergies demonstrated between ErbB2 blockade and DNA-damaging drugs, the synergy between the irreversible EGFR inhibitor and cisplatin does not appear to involve the repair of DNA-cisplatin adducts. Given the current clinical data, this combination may be of more than theoretical interest.