The increasing cost of the basic foods required to promote health in Queensland

Objective: To assess changes in the cost and availability of a standard basket of healthy food items (the Healthy Food Access Basket [HFAB]) in Queensland over time. Design and participants: A series of four cross-sectional surveys (in 1998, 2000, 2001 and 2004) describing the cost and availability of foods in the HFAB over time. In the latest survey, 97 Queensland food stores across the five Australian Bureau of Statistics remoteness categories were compared. Main outcome measures: Cost comparisons for HFAB items by remoteness category for the 97 stores surveyed in 2004; changes in cost and availability of foods in the 81 stores surveyed since 2000; comparisons of food prices in the 56 stores surveyed in 1998, 2000, 2001 and 2004. Results: In 2004, the Queensland mean cost of the HFAB was $395.28 a fortnight. The cost of the HFAB was 29.6%($113.89) higher in “very remote” areas than in “major cities” (P<0.001). Between 2001 and 2004, the Queensland mean cost of the HFAB increased by 14.0% ($48.45), while in very remote areas the cost increased by 18.0% ($76.93) (P<0.001). Since 2000, the annualised per cent increase in cost of the HFAB has been higher than the increase in Consumer Price Index for food in Brisbane. The cost of healthy foods has risen more than the cost of some less nutritious foods, so that the latter are now relatively more affordable. Conclusions: Consumers, particularly those in very remote locations, need to pay substantially more for basic healthy foods than they did a few years ago. Higher prices are likely to be a barrier to good health among people of low socioeconomic status and other vulnerable groups. Interventions to make basic healthy food affordable and accessible to all would help reduce the high burden of chronic disease.

Education of health professionals for preventing diabetic foot ulceration (Protocol)

This is the protocol for a review and there is no abstract. The objectives are as follows: To investigate the effects of educational interventions on the behaviour and clinical practice of health professionals, and subsequent patient outcomes related to prevention of foot ulceration in people with diabetes.

A longitudinal study of the impact of chronic psychological stress on health-related quality of life and clinical biomarkers : protocol for the Australian Healthy Aging of Women Study

BACKGROUND: Despite advancements in our understanding of the importance of stress reduction in achieving good health, we still only have limited insight into the impact of stress on cellular function. Recent studies have suggested that exposure to prolonged psychological stress may alter an individual's physiological responses, and contribute to morbidity and mortality. This paper presents an overview of the study protocol we are using to examine the impact of life stressors on lifestyle factors, health-related quality of life and novel and established biomarkers of stress in midlife and older Australian women.The primary aim of this study is to explore the links between chronic psychological stress on both subjective and objective health markers in midlife and older Australian women. The study examines the extent to which exposure frightening, upsetting or stressful events such as natural disasters, illness or death of a relative, miscarriage and relationship conflict is correlated with a variety of objective and subjective health markers.Methods/design: This study is embedded within the longitudinal Healthy Aging of Women's study which has collected data from midlife and older Australian women at 5 yearly intervals since 2001, and uses the Allostastic model of women's health by Groer and colleagues in 2010. The current study expands the focus of the HOW study and will assess the impact of life stressors on quality of life and clinical biomarkers in midlife and older Australian women to explain the impact of chronic psychological stress in women. DISCUSSION: The proposed study hypothesizes that women are at increased risk of exposure to multiple or repeated stressors, some being unique to women, and the frequency and chronicity of stressors increases women's risk of adverse health outcomes. This study aims to further our understanding of the relationships between stressful life experiences, perceived quality of life, stress biomarkers, chronic illness, and health status in women.

Sustainability of a successful health and nutrition program in a remote Aboriginal community

OBJECTIVE: To assess the long term effect of a nutrition program in a remote Aboriginal community (Minjilang). DESIGN: Evaluation of nutritional outcomes over the three years before and the three years after a health and nutrition program that ran from June 1989 to June 1990. Turnover of food items at the community store was used as a measure of dietary intake at Minjilang and a comparison community. SETTING: A community of about 150 Aboriginal people live at Minjilang on Croker Island, 240 km north-east of Darwin. A similar community of about 300 people on another island was used as the comparison. RESULTS: The program produced lasting improvements in dietary intake of most target foods (including fruit, vegetables and wholegrain bread) and nutrients (including folate, ascorbic acid and thiamine). Sugar intake fell in both communities before the program, but the additional decrease in sugar consumption during the program at Minjilang "rebounded" in the next year. Dietary improvements in the comparison community were delayed and smaller than at Minjilang. CONCLUSIONS: The success of the program at Minjilang was linked to an ongoing process of social change, which in turn provided a stimulus for dietary improvement in the comparison community. When Aboriginal people themselves control and maintain ownership of community-based intervention programs, nutritional improvements can be initiated and sustained.

Survival tucker : improved diet and health indicators in an Aboriginal community

The poor nutritional status of Aboriginal Australians is a serious and complex public health concern. We describe an unusually successful health and nutrition project initiated by the people of Minjilang, which was developed, implemented and evaluated with the community. Apparent community dietary intake, assessed by the ‘store-turnover’ method, and biochemical, anthropometric and haematological indicators of health and nutritional status were measured before intervention and at three-monthly intervals during the intervention year. Following intervention, there was a significant decrease in dietary intake of sugar and saturated fat, an increase in micronutrient density, corresponding improvements in biochemical indices (for example, a 12 per cent decrease in mean serum cholesterol, increases in serum and red cell folate, serum vitamin B6 and plasma ascorbic acid), decrease in mean systolic and diastolic blood pressures, a normalisation of body mass index, and a normalisation of haematologic indices. The success of this project demonstrates that Aboriginal communities can bring about improvements in their generally poor nutritional status, and that the store-turnover method provides a valid, inexpensive and noninvasive method for evaluating the resultant changes in community diet. Although the project was undoubtedly effective in the short term, further work is in progress to assess individual strategies with respect to sustainability, cost-effectiveness and generalisability.

The potential role of lycopene for the prevention and therapy of prostate cancer : from molecular mechanisms to clinical evidence

Lycopene is a phytochemical that belongs to a group of pigments known as carotenoids. It is red, lipophilic and naturally occurring in many fruits and vegetables, with tomatoes and tomato-based products containing the highest concentrations of bioavailable lycopene. Several epidemiological studies have linked increased lycopene consumption with decreased prostate cancer risk. These findings are supported by in vitro and in vivo experiments showing that lycopene not only enhances the antioxidant response of prostate cells, but that it is even able to inhibit proliferation, induce apoptosis and decrease the metastatic capacity of prostate cancer cells. However, there is still no clearly proven clinical evidence supporting the use of lycopene in the prevention or treatment of prostate cancer, due to the only limited number of published randomized clinical trials and the varying quality of existing studies. The scope of this article is to discuss the potential impact of lycopene on prostate cancer by giving an overview about its molecular mechanisms and clinical effects. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

Delineating breast cancer cell interactions with engineered bone microenvironments

The mechanisms leading to colonization of metastatic breast cancer cells (BCa) in the skeleton are still not fully understood. Here, we demonstrate that mineralized extracellular matrices secreted by primary human osteoblasts (hOBM) modulate cellular processes associated with BCa colonization of bone. A panel of four BCa cell lines of different bone-metastatic potential (T47D, SUM1315, MDA-MB-231, and the bone-seeking subline MDA-MB-231BO) was cultured on hOBM. After 3 days, the metastatic BCa cells had undergone morphological changes on hOBM and were aligned along the hOBM's collagen type I fibrils that were decorated with bone-specific proteins. In contrast, nonmetastatic BCa cells showed a random orientation on hOBM. Atomic force microscopy-based single-cell force spectroscopy revealed that the metastatic cell lines adhered more strongly to hOBM compared with nonmetastatic cells. Function-blocking experiments indicated that β1-integrins mediated cell adhesion to hOBM. In addition, metastatic BCa cells migrated directionally and invaded hOBM, which was accompanied by enhanced MMP-2 and -9 secretion. Furthermore, we observed gene expression changes associated with osteomimickry in BCa cultured on hOBM. As such, osteopontin mRNA levels were significantly increased in SUM1315 and MDA-MB-231BO cells in a β1-integrin-dependent manner after growing for 3 days on hOBM compared with tissue culture plastic. In conclusion, our results show that extracellular matrices derived from human osteoblasts represent a powerful experimental platform to dissect mechanisms underlying critical steps in the development of bone metastases.

Breast cancer cells induce osteolytic bone lesions in vivo through a reduction in osteoblast activity in mice

Bone metastases are severely debilitating and have a significant impact on the quality of life of women with metastatic breast cancer. Treatment options are limited and in order to develop more targeted therapies, improved understanding of the complex mechanisms that lead to bone lesion development are warranted. Interestingly, whilst prostate-derived bone metastases are characterised by mixed or osteoblastic lesions, breast-derived bone metastases are characterised by osteolytic lesions, suggesting unique regulatory patterns. This study aimed to measure the changes in bone formation and bone resorption activity at two time-points (18 and 36 days) during development of the bone lesion following intratibial injection of MDA-MB-231 human breast cancer cells into the left tibiae of Severely Combined Immuno-Deficient (SCID) mice. The contralateral tibia was used as a control. Tibiae were extracted and processed for undecalcified histomorphometric analysis. We provide evidence that the early bone loss observed following exposure to MDA-MB-231 cells was due to a significant reduction in mineral apposition rate, rather than increased levels of bone resorption. This suggests that osteoblast activity was impaired in the presence of breast cancer cells, contrary to previous reports of osteoclast-dependent bone loss. Furthermore mRNA expression of Dickkopf Homolog 1 (DKK-1) and Noggin were confirmed in the MDA-MB-231 cell line, both of which antagonise osteoblast regulatory pathways. The observed bone loss following injection of cancer cells was due to an overall thinning of the trabecular bone struts rather than perforation of the bone tissue matrix (as measured by trabecular width and trabecular separation, respectively), suggesting an opportunity to reverse the cancer-induced bone changes. These novel insights into the mechanisms through which osteolytic bone lesions develop may be important in the development of new treatment strategies for metastatic breast cancer patients.

Metastasis of ovarian cancer is mediated by kallikrein related peptidases

Ovarian cancer, in particular epithelial ovarian cancer (EOC), is commonly diagnosed when the tumor has metastasized into the abdominal cavity with an accumulation of ascites fluid. Combining histopathology and genetic variations, EOC can be sub-grouped into Type-I and Type-II tumors, of which the latter are more aggressive and metastatic. Metastasis and chemoresistance are the key events associated with the tumor microenvironment that lead to a poor patient outcome. Kallikrein-related peptidases (KLKs) are aberrantly expressed in EOC, in particular, in the more metastatic Type-II tumors. KLKs are a family of 15 serine proteases that are expressed in diverse human tissues and involved in various patho-physiological processes. As extracellular enzymes, KLKs function in the hydrolysis of growth factors, proteases, cell membrane bound receptors, adhesion proteins, and cytokines initiating intracellular signaling pathways and their downstream events. High KLK levels are differentially associated with the prognosis of ovarian cancer patients, suggesting that they not only have application as biomarkers but also function in disease progression, and therefore are potential therapeutic targets. Recent studies have demonstrated the function of these proteases in promoting and/or suppressing the invasive behavior of ovarian cancer cells in metastasis in vitro and in vivo. Both conventional cell culture methods and three-dimensional platforms have been applied to mimic the ovarian cancer microenvironment of patients, such as the solid stromal matrix and ascites fluid. Here we summarize published studies to provide an overview of our understanding of the role of KLKs in EOC, and to lay the foundation for future research directions.

A bioengineered 3D ovarian cancer model for the assessment of peptidase-mediated enhancement of spheroid growth and intraperitoneal spread

Cancer-associated proteases promote peritoneal dissemination and chemoresistance in malignant progression. In this study, kallikrein-related peptidases 4, 5, 6, and 7 (KLK4-7)-cotransfected OV-MZ-6 ovarian cancer cells were embedded in a bioengineered three-dimensional (3D) microenvironment that contains RGD motifs for integrin engagement to analyze their spheroid growth and survival after chemotreatment. KLK4-7-cotransfected cells formed larger spheroids and proliferated more than controls in 3D, particularly within RGD-functionalized matrices, which was reduced upon integrin inhibition. In contrast, KLK4-7-expressing cell monolayers proliferated less than controls, emphasizing the relevance of the 3D microenvironment and integrin engagement. In a spheroid-based animal model, KLK4-7-overexpression induced tumor growth after 4 weeks and intraperitoneal spread after 8 weeks. Upon paclitaxel administration, KLK4-7-expressing tumors declined in size by 91% (controls: 87%) and showed 90% less metastatic outgrowth (controls: 33%, P<0.001). KLK4-7-expressing spheroids showed 53% survival upon paclitaxel treatment (controls: 51%), accompanied by enhanced chemoresistance-related factors, and their survival was further reduced by combination treatment of paclitaxel with KLK4/5/7 (22%, P=0.007) or MAPK (6%, P=0.006) inhibition. The concomitant presence of KLK4-7 in ovarian cancer cells together with integrin activation drives spheroid formation and proliferation. Combinatorial approaches of paclitaxel and KLK/MAPK inhibition may be more efficient for late-stage disease than chemotherapeutics alone as these inhibitory regimens reduced cancer spheroid growth to a greater extent than paclitaxel alone.

Secretome and degradome profiling shows that Kallikrein-related peptidases 4, 5, 6, and 7 induce TGFβ-1 signaling in ovarian cancer cells

Kallikrein-related peptidases, in particular KLK4, 5, 6 and 7 (4-7), often have elevated expression levels in ovarian cancer. In OV-MZ-6 ovarian cancer cells, combined expression of KLK4-7 reduces cell adhesion and increases cell invasion and resistance to paclitaxel. The present work investigates how KLK4-7 shape the secreted proteome ("secretome") and proteolytic profile ("degradome") of ovarian cancer cells. The secretome comparison consistently identified >900 proteins in three replicate analyses. Expression of KLK4-7 predominantly affected the abundance of proteins involved in cell-cell communication. Among others, this includes increased levels of transforming growth factor β-1 (TGFβ-1). KLK4-7 co-transfected OV-MZ-6 cells share prominent features of elevated TGFβ-1 signaling, including increased abundance of neural cell adhesion molecule L1 (L1CAM). Augmented levels of TGFβ-1 and L1CAM upon expression of KLK4-7 were corroborated in vivo by an ovarian cancer xenograft model. The degradomic analysis showed that KLK4-7 expression mostly affected cleavage sites C-terminal to arginine, corresponding to the preference of kallikreins 4, 5 and 6. Putative kallikrein substrates include chemokines, such as growth differentiation factor 15 (GDF 15) and macrophage migration inhibitory factor (MIF). Proteolytic maturation of TGFβ-1 was also elevated. KLK4-7 have a pronounced, yet non-degrading impact on the secreted proteome, with a strong association between these proteases and TGFβ-1 signaling in tumor biology. © 2013 Federation of European Biochemical Societies.

PITX2 and non-canonical Wnt pathway interaction in metastatic prostate cancer

The non-canonical Wnt pathway, a regulator of cellular motility and morphology, is increasingly implicated in cancer metastasis. In a quantitative PCR array analysis of 84 Wnt pathway associated genes, both non-canonical and canonical pathways were activated in primary and metastatic tumors relative to normal prostate. Expression of the Wnt target gene PITX2 in a prostate cancer (PCa) bone metastasis was strikingly elevated over normal prostate (over 2,000-fold) and primary prostate cancer (over 200-fold). The elevation of PITX2 protein was also evident on tissue microarrays, with strong PITX2 immunostaining in PCa skeletal and, to a lesser degree, soft tissue metastases. PITX2 is associated with cell migration during normal tissue morphogenesis. In our studies, overexpression of individual PITX2A/B/C isoforms stimulated PC-3 PCa cell motility, with the PITX2A isoform imparting a specific motility advantage in the presence of non-canonical Wnt5a stimulation. Furthermore, PITX2 specific shRNA inhibited PC-3 cell migration toward bone cell derived chemoattractant. These experimental results support a pivotal role of PITX2A and non-canonical Wnt signaling in enhancement of PCa cell motility, suggest PITX2 involvement in homing of PCa to the skeleton, and are consistent with a role for PITX2 in PCa metastasis to soft and bone tissues. Our findings, which significantly expand previous evidence that PITX2 is associated with risk of PCa biochemical recurrence, indicate that variation in PITX2 expression accompanies and may promote prostate tumor progression and metastasis.

Serum HE4 as a prognostic marker in endometrial cancer : a population based study

Objective HE4 has emerged as a promising biomarker in gynaecological oncology. The purpose of this study was to evaluate serum HE4 as a biomarker for high-risk phenotypes in a population-based endometrial cancer cohort. Methods Peri-operative serum HE4 and CA125 were measured in 373 patients identified from the prospective Australian National Endometrial Cancer Study (ANECS). HE4 and CA125 were quantified on the ARCHITECT instrument in a clinically accredited laboratory. Receiver operator curves (ROC), Spearman rank correlation coefficient, and chi-squared and Mann–Whitney tests were used for statistical analysis. Survival analysis was performed using Kaplan–Meier and Cox multivariate regression analyses. Results Median CA125 and HE4 levels were higher in stage III and IV tumours (p < 0.001) and in tumours with outer-half myometrial invasion (p < 0.001). ROC analysis demonstrated that HE4 (area under the curve (AUC) = 0.76) was a better predictor of outer-half myometrial invasion than CA125 (AUC = 0.65), particularly in patients with low-grade endometrioid tumours (AUC 0.77 vs 0.64 for CA125). Cox multivariate analysis demonstrated that elevated HE4 was an independent predictor of recurrence-free survival (HR = 2.40, 95% CI 1.19–4.83, p = 0.014) after adjusting for stage and grade of disease, particularly in the endometrioid subtype (HR = 2.86, 95% CI 1.25–6.51, p = 0.012). Conclusion These findings demonstrate the utility of serum HE4 as a prognostic biomarker in endometrial cancer in a large, population-based study. In particular they highlight the utility of HE4 for pre-operative risk stratification to identify high-risk patients within low-grade endometrioid endometrial cancer patients who might benefit from lymphadenectomy.