Developing a three-dimensional in-vitro cell culture model for studying breast and prostate cancer using starPEG-heparin hydrogels

Introduction Hydrogels prepared from poly(ethylene glycol) (PEG) and maleimide-functionalized heparin provide a potential matrix for use in developing three dimensional (3D) models. We have previously demonstrated that these hydrogels support the cultivation of human umbilical vein endothelial cells (HUVECs) (1). We extend this body of work to study the ability to create an extracellular matrix (ECM)-like model to study breast and prostate cancer cell growth in 3D. Also, we investigate the ability to produce a tri-culture mimicking tumour angiogenesis with cancer spheroids, HUVECs and mesenchymal stem cells (MSC). Materials and Methods The breast cancer cell lines, MCF-7 and MDA-MB-231, and prostate cancer cell lines, LNCaP and PC3, were seeded into starPEG-heparin hydrogels and grown for 14 Days to analyse the effects of varying hydrogel stiffness on spheroid development. Resulting hydrogel constructs were analyzed via Alamar Blue assays, light microscopy, and immunofluorescence staining for cytokeratin 8/18, Ki67 and E-Cadherin. Cancer cell lines were then pre-grown in hydrogels for 5-7 days and then re-seeded into starPEG-heparin hydrogels functionalised with RGD, SDF-1, bFGF and VEGF as spheroids with HUVECs and MSC and grown for 14 days as a tri-culture in Endothelial Cell Growth Medium (ECGM; Promocell). Cell lines were also seeded as a single cell suspension into the functionalised tri-culture system. Cultures were fixed in 4% paraformaldehyde and analysed via immunostaining for Von Willebrand Factor and CD31, as well as the above mentioned markers, and observed using confocal microscopy. Results Cultures prepared in MMP-cleavable starPEG-heparin hydrogels display spheroid formation in contrast to adherent growth on tissue culture plastic. Small differences were visualised in cancer spheroid growth between different gel stiffness across the range of cell lines. Cancer cell lines were able to be co-cultivated with HUVECs and MSC. HUVEC tube formation and cancer line spheroid formation occured after 3-4 days. Interaction was visualised between tumours and HUVECs via confocal microscopy. Slightly increased interaction was seen between cancer tumours and micro-vascular tubes when seeded as single cells compared with the pre-formed spheroid approach. Further studies intend to utilise cytokine gradients to further optimise the ECM environment of in situ tumour angiogenesis. Discussion and Conclusions Our results confirm the suitability of hydrogels constructed from starPEG-heparin for HUVECs and MSC co-cultivation with cancer cell lines to study cell-cell and cell-matrix interactions in a 3D environment. This represents a step forward in the development of 3D culture models to study the pathomechanisms of breast and prostate cancer. References 1. Tsurkan MV, Chwalek K, Prokoph S, Zieris A, Levental KR, Freudenberg U, Werner C. Advanced Materials. 25, 2606-10, 2013. Disclosures The authors declare no conflicts of interest

Food neophobia and its association with diet quality and weight in children aged 24 months : a cross sectional study

Background Food neophobia, the rejection of unknown or novel foods, may result in poor dietary patterns. This study investigates the cross-sectional relationship between neophobia in children aged 24 months and variety of fruit and vegetable consumption, intake of discretionary foods and weight. Methods Secondary analysis of data from 330 parents of children enrolled in the NOURISH RCT (control group only) and SAIDI studies was performed using data collected at child age 24 months. Neophobia was measured at 24 months using the Child Food Neophobia Scale (CFNS). The cross-sectional associations between total CFNS score and fruit and vegetable variety, discretionary food intake and BMI (Body Mass Index) Z-score were examined via multiple regression models; adjusting for significant covariates. Results At 24 months, more neophobic children were found to have lower variety of fruits (β=-0.16, p=0.003) and vegetables (β=-0.29, p<0.001) but have a greater proportion of daily energy from discretionary foods (β=0.11, p=0.04). There was no significant association between BMI Z-score and CFNS score. Conclusions Neophobia is associated with poorer dietary quality. Results highlight the need for interventions to (1) begin early to expose children to a wide variety of nutritious foods before neophobia peaks and (2) enable health professionals to educate parents on strategies to overcome neophobia.

Exploring urban consumers’ attitudes and intentions to purchase local food in Chile

Although local food consumption is growing in importance there remains a lack of research addressing local food consumption preferences in less-developed countries. This paper aims to examine the drivers of local food purchase intentions for Chilean consumers. A model of local food behavioral intention was developed from consumer behavior theory. The model was tested using structural equation modeling with data from Chilean shoppers located in Santiago (n=283). The analysis revealed that Chilean consumers are willing to purchase local food based on their positive attitude towards buying local food and their feelings of connectedness with the environment, but not because they have a desire to support local businesses. These findings have implications for retailers, marketers and food producers.

Mobile interaction design approaches for reducing domestic food waste

This thesis is a trans-disciplinary study of domestic food waste in Australia. Firstly, it examines why consumers are prone to waste food. Secondly, it explores several situated design interventions to reduce domestic food waste by informing consumer food supply and location awareness, and improving the level of food literacy among consumers. The thesis outcomes have implications for academic and industry domains within the fields of Human-Computer Interaction, urban informatics, environmental sustainability, food security and public health.

Literacy and Digital Culture in the Early Years

In this chapter we present data drawn from observations of kindergarten children using iPads and talk with the children, their parents/guardians and teachers. We identify a continuum of practices that extends from ‘educational apps’ teaching handwriting, sight words and so forth to uses of the iPad as a device for multimodal literacy development and substantive conversation around children’s creative work. At the current time high stakes testing and the implementation of the Australian Curriculum are prompting new public and professional conversations about literacy and digital technology. The iPad is construed as both cause of and solution to problems of traditional literacy education. In this context we describe the literacies enabled by educational software available on iPads. We higlight the time constraints which bore on teachers' capacity to enact their visions of literacy education through the iPad platform and suggest ways of reflecting on responses to this constraint.

Evolution of the docklands food hub : a design-led innovation approach to food sovereignty through local food systems

Access to nutritious, safe and culturally appropriate food is a basic human right (Mechlem, 2004). Food sovereignty defines this right through the empowerment of the people to redefine food and agricultural systems, and through ecologically sustainable production methods. At the heart of the food sovereignty movement are the interests of producers, distributors and consumers, rather than the interests of markets and corporations, which dominate the current globalized food system (Hinrichs, 2003). Food sovereignty challenges designers to enable people to innovate the food system. We are yet to develop economically viable solutions for scaling projects and providing citizens, governments and business with tools to develop and promote projects to innovate food systems and promote food sovereignty (Meroni, 2011; Murray, Caulier-Grice and Mulgan, 2010). This article examines how a design-led approach to innovation can assist in the development of new business models and ventures for local food systems: this is presented through an emerging field of research ‘Design-Led Food Communities’. Design-Led Food Communities enables citizens, governments and business to innovate local food projects through the application of design. This article reports on the case study of the Docklands Food Hub Project in Melbourne, Australia. Preliminary findings demonstrate valued outcomes, but also a deficiency in the design process to generate food solutions collaboratively between government, business and citizens.

Culture in Business Process Management: How cultural values determine BPM success

There is consensus among practitioners and academics that culture is a critical factor that is able to determine success or failure of BPM initiatives. Yet, culture is a topic that seems difficult to grasp and manage. This may be the reason for the overall lack of guidance on how to address this topic in practice. We have conducted in-depth research for more than three years to examine why and how culture is relevant to BPM. In this chapter, we introduce a framework that explains the role of culture in BPM. We also present the relevant cultural values that compose a BPM culture, and we introduce a tool to examine the supportiveness of organizational cultures for BPM. Our research results provide the basis for further empirical analyses on the topic and support practitioners in the management of culture as an important factor in BPM initiatives.

Household food insecurity, diet, and weight status in a disadvantaged district of Ho Chi Minh City, Vietnam: A cross-sectional study

Background Food security exists when all people, at all times, have physical, economic and socially acceptable access to safe, sufficient, and adequately nutritious food in order to meet their dietary needs for an active and healthy life. For high income countries and those experiencing the nutrition transition, food security is not only about the quantity of available food but also the nutritional quality as related to over- and under-nutrition. Vietnam is currently undergoing this nutrition transition, and as a result the relationship between food insecurity, socio-demographic factors and weight status is complex. The primary objective of this study was to therefore measure the prevalence of household food insecurity in a disadvantaged urban district in Ho Chi Minh City (HCMC) in Vietnam using a more comprehensive tool. This study also aims to examine the relationships between food insecurity and socio-demographic factors, weight status, and food intakes. Methods A cross-sectional study was conducted using multi-stage sampling. Adults who were mainly responsible for cooking were interviewed in 250 households. Data was collected on socioeconomic and demographic factors using previously validated tools. Food security was assessed using the Latin American and Caribbean Household Food Security Scale (ELCSA) tool and households were categorized as food secure or mildly, moderately or severely food insecure. Questions regarding food intake were based on routinely used and validated questions in HCMC, weight status was self-reported. Results Cronbach’s alpha coefficient was 0.87, showing the ELCSA had a good internal reliability. Approximately 34.4% of households were food insecure. Food insecurity was inversely related to total household income (OR = 0.09, 95% CI = 0.04 - 0.22) and fruit intakes (OR = 2.2, 95% CI 1.31 - 4.22). There was no association between weight and food security status. Conclusions Despite rapid industrialization and modernization, food insecurity remains an important public health issue in large urban areas of HCMC, suggesting that strategies to address food insecurity should be implemented in urban settings, and not just rural locations. Fruit consumption among food insecure households may be compromised because of financial difficulties, which may lead to poorer health outcomes particularly related to non-communicable disease prevention and management.

The culture of young women's drinking: Implications for developing effective policing strategies. Report to National Drug Strategy Law Enforcement Committee

Alcohol-related mortality and morbidity represents a substantial financial burden on communities across the world. Adolescence and young adulthood is a peak period for heavy episodic alcohol consumption, with over a third of all people aged 14-19 years having been at risk of acute alcoholrelated harm at least once in the previous 12 months (Australian Institute of Health and Welfare [AIHW], 2011). Excessive alcohol consumption has long been seen as a male problem; however, a gradual shift towards a social acceptance of female drunkenness has narrowed the gap in drinking quantity and style between men and women (Grucza, Bucholz, Rice, & Bierut, 2008). The presented data point to the vulnerability of women to the consequences of acute alcohol intoxication and indicate that alcohol-related offending by women is on the rise. Taken together, these findings reveal that alcohol-related harms and aggression for young women are becoming more prevalent and problematic. This report addressed these issues from a policing perspective...

Growing food in the city : Design ideations for urban residential gardeners

Urban agriculture refers to the production of food in urban and peri-urban spaces. It can contribute positively to health and food security of a city, while also reducing ‘food miles.’ It takes on many forms, from the large and organised community garden, to the small and discrete backyard or balcony. This study focuses on small-scale food production in the form of residential gardening for home or personal use. We explore opportunities to support people’s engagement in urban agriculture via human-computer interaction design. This research presents the findings and HCI design insights from our study of residential gardeners in Brisbane, Australia. By exploring their understanding of gardening practice with a human-centred design approach, we present six key themes, highlighting opportunities and challenges relating to available time and space; the process of learning and experimentation; and the role of existing online platforms to support gardening practice. Finally we discuss the overarching theme of shared knowledge, and how HCI could improve community engagement and gardening practice.

3D cultures of prostate cancer cells cultured in a novel high-throughput culture platform are more resistant to chemotherapeutics compared to cells cultured in monolayer

Despite monolayer cultures being widely used for cancer drug development and testing, 2D cultures tend to be hypersensitive to chemotherapy and are relatively poor predictors of whether a drug will provide clinical benefit. Whilst generally more complicated, three dimensional (3D) culture systems often better recapitulate true cancer architecture and provide a more accurate drug response. As a step towards making 3D cancer cultures more accessible, we have developed a microwell platform and surface modification protocol to enable high throughput manufacture of 3D cancer aggregates. Herein we use this novel system to characterize prostate cancer cell microaggregates, including growth kinetics and drug sensitivity. Our results indicate that prostate cancer cells are viable in this system, however some non-cancerous prostate cell lines are not. This system allows us to consistently control for the presence or absence of an apoptotic core in the 3D cancer microaggregates. Similar to tumor tissues, the 3D microaggregates display poor polarity. Critically the response of 3D microaggregates to the chemotherapeutic drug, docetaxel, is more consistent with in vivo results than the equivalent 2D controls. Cumulatively, our results demonstrate that these prostate cancer microaggregates better recapitulate the morphology of prostate tumors compared to 2D and can be used for high-throughput drug testing.

Using culture to manage the transition into university: Conceptualising the dynamics of withdrawal and engagement

This conceptual paper explored the purposes of using culture in the process of coping with stress by looking how first year undergraduate students used cultural elements and activities to aid their transition into university. Results supported two key conceptualisations of the use of culture. Firstly, results indicated that students used culture either for withdrawal purposes, i.e., for escaping from the stressful situation, or for engagement purposes, i.e., for actively engaging with the stressful situation. Secondly, the results suggested three different forms of using culture to engage with stressful situations: mood management, learning, and personal interaction. While the results of the study resonate with the distinction between avoidance versus approach-oriented coping strategies that are widely explored in the stress and coping literature, they also suggest that the relationship between withdrawal and engagement might be dynamic with those two strategies serving distinct purposes in the process of coping with stress. The paper thus suggests that there is a need to develop process-oriented models of coping that would allow identifying patterns in the way people fluctuate between withdrawal and engagement that support and facilitate their personal growth and development.