Assessment of factors associated with PSA level in prostate cancer cases and controls from three geographical regions.

It is being debated whether prostate-specific antigen (PSA)-based screening effectively reduces prostate cancer mortality. Some of the uncertainty could be related to deficiencies in the age-based PSA cut-off thresholds used in screening. Current study considered 2779 men with prostate cancer and 1606 men without a cancer diagnosis, recruited for various studies in New Zealand, US, and Taiwan.

Effect of androgen deprivation therapy on serum levels of sclerostin, Dickkopf-1, and osteoprotegerin: a cross-sectional and longitudinal analysis.

Androgen deprivation therapy (ADT) for men with prostate cancer (PCa) results in accelerated bone loss and increased risk of bone fracture. The aim of the present study was to evaluate serum bone markers-sclerostin, Dickkopf-1 (DKK-1) and osteoprotegerin (OPG), in a cohort of 88 PCa patients without known bone metastases, managed with and without ADT, and to analyse their relationship with bone mineral density (BMD) and sex steroids. The cross-sectional analysis between acute-, chronic- and former-ADT groups and PCa controls showed that sclerostin and OPG levels significantly differed between them (p = 0.

Selenium Supplementation and Prostate Health in a New Zealand Cohort.

Background: There is variable reporting on the benefits of a 200 μg/d selenium supplementation towards reducing prostate cancer impacts. The current analysis is to understand whether stratified groups receive supplementation benefits on prostate health.

Methods: 572 men were supplemented with 200 µg/d selenium as selinized yeast for six months, and 481 completed the protocol.

Interaction between leukocyte aldo-keto reductase 1C3 activity, genotypes, biological, lifestyle and clinical features in a prostate cancer cohort from New Zealand.

Introduction: Aldo-keto reductase 1C3 (AKR1C3) is known for multiple functions including its catalytic activity towards producing extra-testicular androgen. The present study is towards understanding interaction between biological, lifestyle and genetic impacts of AKR1C3 and their influence on clinical factors in a prostate cancer (PC) cohort from New Zealand (NZ).

Method: Characteristics of 516 PC patients were collected from the Auckland Regional Urology Facility, NZ.

Influence of lifestyle and genetic variants in the aldo-keto reductase 1C3 rs12529 polymorphism in high-risk prostate cancer detection variability assessed between US and New Zealand cohorts.

Introduction: The prostate-specific antigen (PSA) based prostate cancer (PC) screening is currently being debated. The current assessment is to understand the variability of detecting high-risk PC in a NZ cohort in comparison to a US cohort with better PSA screening facilities. Aldo-keto reductase 1C3 (AKR1C3) is known for multiple functions with a potential to regulate subsequent PSA levels.

Effect of Androgen Deprivation Therapy on Bone Mineral Density in a Prostate Cancer Cohort in New Zealand: A Pilot Study.

Introduction: Reduction in bone mineral density (BMD) is a common side effect of androgen deprivation therapy (ADT). We aimed to examine the cross-sectional and longitudinal variation in BMD and associated bone markers in patients with nonmetastatic prostate cancer (PCa) managed with and without ADT.

Methods: Bone mineral density of the total body, lumbar spine, femoral neck, ultradistal forearm, and one-third distal radius was measured in 88 patients with PCa without bone metastases at baseline and at 6 months.

Environmental factors and risk of aggressive prostate cancer among a population of New Zealand men - a genotypic approach.

Prostate cancer is one of the most significant health concerns for men worldwide. Numerous researchers carrying out molecular diagnostics have indicated that genetic interactions with biological and behavioral factors play an important role in the overall risk and prognosis of this disease. Single nucleotide polymorphisms (SNPs) are increasingly becoming strong biomarker candidates to identify susceptibility to prostate cancer.

Quality of life effects of androgen deprivation therapy in a prostate cancer cohort in New Zealand: can we minimize effects using a stratification based on the aldo-keto reductase family 1, member C3 rs12529 gene polymorphism?

Background: Androgen deprivation therapy (ADT) is an effective palliation treatment in men with advanced prostate cancer (PC). However, ADT has well documented side effects that could alter the patient's health-related quality of life (HRQoL). The current study aims to test whether a genetic stratification could provide better knowledge for optimising ADT options to minimize HRQoL effects.

Benefits of Selenium Supplementation on Leukocyte DNA Integrity Interact with Dietary Micronutrients: A Short Communication.

A male cohort from New Zealand has previously shown variability in Selenium (Se) supplementation effects on measured biomarkers. The current analysis is to understand the reasons for variability of the H₂O₂-induced DNA damage recorded after Se supplementation. We have looked at the variation of demographic, lifestyle, medication, genetic and dietary factors and biomarkers measured at baseline and post-supplementation in these two extreme subgroups A and B.

Inoculation with enterococci does not affect colon inflammation in the multi-drug resistance 1a-deficient mouse model of IBD.

Background: Intestinal bacteria are thought to play a role in the pathogenesis of human inflammatory bowel disease (IBD). We investigated whether oral inoculation with specific intestinal bacteria increased colon inflammation in the multi-drug resistance 1a-deficient (Mdr1a (-/-) ) mouse model of IBD.

Methods: Five-week-old Mdr1a (-/-) mice (FVB background) and FVB mice were randomly assigned to one of two treatment groups (Control or Inoculation, n = 12 per group).

An investigation into the association between DNA damage and dietary fatty acid in men with prostate cancer.

Prostate cancer is a growing problem in New Zealand and worldwide, as populations adopt a Western style dietary pattern. In particular, dietary fat is believed to be associated with oxidative stress, which in turn may be associated with cancer risk and development. In addition, DNA damage is associated with the risk of various cancers, and is regarded as an ideal biomarker for the assessment of the influence of foods on cancer.

Transcriptomics to study the effect of a Mediterranean-inspired diet on inflammation in Crohn's disease patients.

Background: Inflammation is an essential immune response; however, chronic inflammation results in disease including Crohn's disease. Therefore, reducing the inflammation can yield a significant health benefit, and one way to achieve this is through diet. We developed a Mediterranean-inspired anti-inflammatory diet and used this diet in a 6-week intervention in a Crohn's disease population.

Gene expression changes in the colon epithelium are similar to those of intact colon during late inflammation in interleukin-10 gene deficient mice.

In addition to their role in absorption and secretion, epithelial cells play an important role in the protection of the colon mucosa from the resident microbiota and are important for the maintenance of homeostasis. Microarray analysis of intact colon samples is widely used to gain an overview of the cellular pathways and processes that are active in the colon during inflammation. Laser microdissection of colon epithelial cells allows a more targeted analysis of molecular pathways in the mucosa, preceding and during inflammation, with potentially increased sensitivity to changes in specific cell populations.

Effects of supplementation with selenium, as selenized yeast, in a healthy male population from New Zealand.

Selenium (Se) supplementation was tested in a group of healthy men from Auckland, New Zealnd with selenized yeast (Selplex, 200 μg/day) as the supplementation mode. A set of biomarkers, including DNA damage levels and seleno-antioxidant enzyme levels, were evaluated at pre- and postsupplementation time points. Supplementation produced significant increases in serum Se levels, red blood cell (RBC) thioredoxin reductase (TR) activity and peroxide-induced DNA damage, when the mean baseline serum Se level was 110 ng/ml.

Selenium and its' role in the maintenance of genomic stability.

Selenium (Se) is an essential micronutrient for humans, acting as a component of the unusual amino acids, selenocysteine (Se-Cys) and selenomethionine (Se-Met). Where Se levels are low, the cell cannot synthesise selenoproteins, although some selenoproteins and some tissues are prioritised over others. Characterised functions of known selenoproteins, include selenium transport (selenoprotein P), antioxidant/redox properties (glutathione peroxidases (GPxs), thioredoxin reductases and selenoprotein P) and anti-inflammatory properties (selenoprotein S and GPx4).

Inhibition or enhancement by 4 Pacific Island food plants against cancers induced by 2 amino-3-methylimidazo[4,5-f]quinoline in male Fischer 344 rats.

A 1-yr carcinogenicity bioassay was conducted in rats fed 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), simultaneously with AIN-76/ high-fat (HF) diet alone, or with 10% starch replaced with kumara, pineapple, coconut, or taro, prepared as for a human diet. All of the non-IQ treated control, kumara, pineapple, or taro but not coconut-fed rats survived to 1 yr. None of the IQ-fed animals survived to 1 yr and although there were minor survival time differences among the groups, none was statistically significant.

Effects of kiwifruit extracts on colonic gene and protein expression levels in IL-10 gene-deficient mice.

Inflammatory bowel disease (IBD) is a collective term for conditions characterised by chronic inflammation of the gastrointestinal tract involving an inappropriate immune response to commensal micro-organisms in a genetically susceptible host. Previously, aqueous and ethyl acetate extracts of gold kiwifruit (Actinidia chinensis) or green kiwifruit (A. deliciosa) have demonstrated anti-inflammatory activity using in vitro models of IBD.

Serum selenium and single-nucleotide polymorphisms in genes for selenoproteins: relationship to markers of oxidative stress in men from Auckland, New Zealand.

There is controversy as to the recommended daily intake of selenium (Se), and whether current New Zealand diets are adequate in this nutrient. Various functional single-nucleotide polymorphisms (SNPs) polymorphisms may affect the efficacy of Se utilisation. These include the glutathione peroxidases GPx1 rs1050450, GPx4 rs713041, as well as selenoproteins SEPP1 rs3877899, SEL15 rs5845, SELS rs28665122 and SELS rs4965373.

Influence of dietary blueberry and broccoli on cecal microbiota activity and colon morphology in mdr1a(-/-) mice, a model of inflammatory bowel diseases.

Objective: Enteric microbiota has been shown to be associated with various pathological conditions such as inflammatory bowel disease (IBD). This study aimed to determine the anti-inflammatory colonic effects of blueberries and broccoli in mdr1a(-/-) mice (IBD mouse model) through modification of microbiota composition in the gastrointestinal tract.

Methods: The mdr1a(-/-) mice were fed either a control diet or the control diet supplemented with either 10% blueberry or broccoli for 21 wk.

Metabolomic analysis reveals differences in urinary excretion of kiwifruit-derived metabolites in a mouse model of inflammatory bowel disease.

The interleukin-10-deficient (IL-10(-/-)) mouse, a model of inflammatory bowel disease (IBD), develops intestinal inflammation unless raised in germ-free conditions. The metabolic effects of consuming extracts from the fruits of yellow (Actinidia chinensis) or green-fleshed (A. deliciosa) kiwifruit that displayed in vitro anti-inflammatory activity were investigated in IL-10(-/-) mice by metabolomic analysis of urine samples.

Comparative effects in rats of intact wheat bran and two wheat bran fractions on the disposition of the mutagen 2-amino-3-methylimidazo[4,5-f]quinoline.

Wheat bran protects against mutations and cancer, but contains different plant cell types that are likely to have different protective effects. We previously described the production and chemical characterisation of an aleurone-rich fraction (ARF) and a pericarp-rich fraction (PRF) from wheat grain. We compared these with whole bran (WB), fed to rats as 10% of a high fat AIN-76 diet.

Molecular Characterization of the Onset and Progression of Colitis in Inoculated Interleukin-10 Gene-Deficient Mice: A Role for PPARalpha.

The interleukin-10 gene-deficient (Il10(-/-)) mouse is a model of human inflammatory bowel disease and Ppara has been identified as one of the key genes involved in regulation of colitis in the bacterially inoculated Il10(-/-) model. The aims were to (1) characterize colitis onset and progression using a histopathological, transcriptomic, and proteomic approach and (2) investigate links between PPARalpha and IL10 using gene network analysis. Bacterial inoculation resulted in severe colitis in Il10(-/-) mice from 10 to 12 weeks of age.

Changes in colon gene expression associated with increased colon inflammation in interleukin-10 gene-deficient mice inoculated with Enterococcus species.

Background: Inappropriate responses to normal intestinal bacteria may be involved in the development of Inflammatory Bowel Diseases (IBD, e.g. Crohn's Disease (CD), Ulcerative Colitis (UC)) and variations in the host genome may mediate this process.

Dietary arachidonic acid-mediated effects on colon inflammation using transcriptome analysis.

Increased levels of n-6 arachidonic acid (AA), a precursor of pro-inflammatory eicosanoids, have been found in the colon mucosa of inflammatory bowel disease patients when compared with healthy subjects. The hypothesis was that dietary AA would aggravate colon inflammation by changing expression of genes in inflammatory signaling pathways. AA-enriched diet was fed to IL10 gene-deficient (Il10-/-) mice, model of a inflammatory bowel disease, and compared with Il10-/- mice fed an oleic acid control diet.

Metabolomic analysis identifies inflammatory and noninflammatory metabolic effects of genetic modification in a mouse model of Crohn's disease.

Interleukin-10 is an immunosuppressive cytokine involved in the regulation of gastrointestinal mucosal immunity toward intestinal microbiota. Interleukin-10-deficient (IL10(-/-)) mice develop Crohn's disease-like colitis unless raised in germ-free conditions. Previous gas chromatography-mass spectrometry (GC-MS) metabolomic analysis revealed urinary metabolite differences between IL10(-/-) and wildtype C57BL/6 mice.