Interactions between human osteoblasts and prostate cancer cells in a novel 3D in vitro model

Cell-cell and cell-matrix interactions play a major role in tumor morphogenesis and cancer metastasis. Therefore, it is crucial to create a model with a biomimetic microenvironment that allows such interactions to fully represent the pathophysiology of a disease for an in vitro study. This is achievable by using three-dimensional (3D) models instead of conventional two-dimensional (2D) cultures with the aid of tissue engineering technology. We are now able to better address the complex intercellular interactions underlying prostate cancer (CaP) bone metastasis through such models. In this study, we assessed the interaction of CaP cells and human osteoblasts (hOBs) within a tissue engineered bone (TEB) construct. Consistent with other in vivo studies, our findings show that intercellular and CaP cell-bone matrix interactions lead to elevated levels of matrix metalloproteinases, steroidogenic enzymes and the CaP biomarker, prostate specific antigen (PSA); all associated with CaP metastasis. Hence, it highlights the physiological relevance of this model. We believe that this model will provide new insights for understanding of the previously poorly understood molecular mechanisms of bone metastasis, which will foster further translational studies, and ultimately offer a potential tool for drug screening. © 2010 Landes Bioscience.

Mineralized human primary osteoblast matrices as a model system to analyse interactions of prostate cancer cells with the bone microenvironment

Prostate cancer metastasis is reliant on the reciprocal interactions between cancer cells and the bone niche/micro-environment. The production of suitable matrices to study metastasis, carcinogenesis and in particular prostate cancer/bone micro-environment interaction has been limited to specific protein matrices or matrix secreted by immortalised cell lines that may have undergone transformation processes altering signaling pathways and modifying gene or receptor expression. We hypothesize that matrices produced by primary human osteoblasts are a suitable means to develop an in vitro model system for bone metastasis research mimicking in vivo conditions. We have used a decellularized matrix secreted from primary human osteoblasts as a model for prostate cancer function in the bone micro-environment. We show that this collagen I rich matrix is of fibrillar appearance, highly mineralized, and contains proteins, such as osteocalcin, osteonectin and osteopontin, and growth factors characteristic of bone extracellular matrix (ECM). LNCaP and PC3 cells grown on this matrix, adhere strongly, proliferate, and express markers consistent with a loss of epithelial phenotype. Moreover, growth of these cells on the matrix is accompanied by the induction of genes associated with attachment, migration, increased invasive potential, Ca2+ signaling and osteolysis. In summary, we show that growth of prostate cancer cells on matrices produced by primary human osteoblasts mimics key features of prostate cancer bone metastases and thus is a suitable model system to study the tumor/bone micro-environment interaction in this disease.

Bioengineered 3D platform to explore cell-ECM interactions and drug resistance of epithelial ovarian cancer cells

The behaviour of cells cultured within three-dimensional (3D) structures rather than onto two-dimensional (2D) culture plastic more closely reflects their in vivo responses. Consequently, 3D culture systems are becoming crucial scientific tools in cancer cell research. We used a novel 3D culture concept to assess cell-matrix interactions implicated in carcinogenesis: a synthetic hydrogel matrix equipped with key biomimetic features, namely incorporated cell integrin-binding motifs (e.g. RGD peptides) and the ability of being degraded by cell-secreted proteases (e.g. matrix metalloproteases). As a cell model, we chose epithelial ovarian cancer, an aggressive disease typically diagnosed at an advanced stage when chemoresistance occurs. Both cell lines used (OV-MZ-6, SKOV-3) proliferated similarly in 2D, but not in 3D. Spheroid formation was observed exclusively in 3D when cells were embedded within hydrogels. By exploiting the design flexibility of the hydrogel characteristics, we showed that proliferation in 3D was dependent on cell-integrin engagement and the ability of cells to proteolytically remodel their extracellular microenvironment. Higher survival rates after exposure to the anti-cancer drug paclitaxel were observed in cell spheroids grown in hydrogels (40-60%) compared to cell monolayers in 2D (20%). Thus, 2D evaluation of chemosensitivity may not reflect pathophysiological events seen in patients. Because of the design flexibility of their characteristics and their stability in long-term cultures (28 days), these biomimetic hydrogels represent alternative culture systems for the increasing demand in cancer research for more versatile, physiologically relevant and reproducible 3D matrices.

Using poster presentations as assessment of work integrated learning

Background / context: The ALTC WIL Scoping Study identified a need to develop innovative assessment methods for work integrated learning (WIL) that encourage reflection and integration of theory and practice within the constraints that result from the level of engagement of workplace supervisors and the ability of academic supervisors to become involved in the workplace. Aims: The aim of this paper is to examine how poster presentations can be used to authentically assess student learning during WIL. Method / Approach: The paper uses a case study approach to evaluate the use of poster presentations for assessment in two internship units at the Queensland University of Technology. The first is a unit in the Faculty of Business where students majoring in advertising, marketing and public relations are placed in a variety of organisations. The second unit is a law unit where students complete placements in government legal offices. Results / Discussion: While poster presentations are commonly used for assessment in the sciences, they are an innovative approach to assessment in the humanities. This paper argues that posters are one way that universities can overcome the substantial challenges of assessing work integrated learning. The two units involved in the case study adopt different approaches to the poster assessment; the Business unit is non-graded and the poster assessment task requires students to reflect on their learning during the internship. The Law unit is graded and requires students to present on a research topic that relates to their internship. In both units the posters were presented during a poster showcase which was attended by students, workplace supervisors and members of faculty. The paper evaluates the benefits of poster presentations for students, workplace supervisors and faculty and proposes some criteria for poster assessment in WIL. Conclusions / Implications: The paper concludes that posters can effectively and authentically assess various learning outcomes in WIL in different disciplines while at the same time offering a means to engage workplace supervisors with academic staff and other students and supervisors participating in the unit. Posters have the ability to demonstrate reflection in learning and are an excellent demonstration of experiential learning and assessing authentically. Keywords: Work integrated learning, assessment, poster presentations, industry engagement.

Adherence to fish oil intervention in patients with chronic kidney disease

Objective: With growing recognition of the role of inflammation in the development of chronic and acute disease, fish oil is increasingly used as a therapeutic agent, but the nature of the intervention may pose barriers to adherence in clinical populations. Our objective was to investigate the feasibility of using a fish oil supplement in hemodialysis patients. ---------- Design: This was a nonrandomized intervention study.---------- Setting: Eligible patients were recruited at the Hemodialysis Unit of Wesley Hospital, Brisbane, Queensland, Australia. Patients The sample included 28 maintenance hemodialysis patients out of 43 eligible patients in the unit. Exclusion criteria included patients regularly taking a fish oil supplement at baseline, receiving hemodialysis for less than 3 months, or being unable to give informed consent.---------- Intervention: Eicosapentaenoic acid (EPA) was administered at 2000 mg/day (4 capsules) for 12 weeks. Adherence was measured at baseline and weekly throughout the study according to changes in plasma EPA, and was further measured subjectively by self-report.---------- Results: Twenty patients (74%) adhered to the prescription based on changes in plasma EPA, whereas an additional two patients self-reported good adherence. There was a positive relationship between fish oil intake and change in plasma EPA. Most patients did not report problems with taking the fish oil. Using the baseline data, it was not possible to characterize adherent patients.---------- Conclusions: Despite potential barriers, including the need to take a large number of prescribed medications already, 74% of hemodialysis patients adhered to the intervention. This study demonstrated the feasibility of using fish oil in a clinical population.

Enhancing the transition of commencing students into university : an institution-wide approach

The importance of the first year experience (FYE) to success at university is well documented and supported with the transition into university regarded as crucial. While there is also support for the notion that a successful FYE should have a whole-of-institution focus and models have been proposed, many institutions still face challenges in achieving institution-wide FYE program implementation. This paper discusses the origins, theoretical and empirical bases and structure of an institution-wide approach to the FYE. It uses a case study of the Transitions In Project (TIP) at the Queensland University of Technology to illustrate how institution-wide FYE program implementation can be achieved and sustained. TIP had four inter-related projects focussing on at-risk students, first year curriculum, learning resources and staff development. The key aim of TIP was to identify good practice and institutionalise it in a sustainable way. The degree of success in achieving this is evaluated.

Cyberbullying in social networking sites and blogs : legal issues for young people and schools

This article examines the social networking phenomenon that has been so readily embraced by school-age adolescents, in the context of its potential to contribute further to the mechanisms for and incidence of cyberbullying amongst school students. Cyberbullying in these online for a, as a misuse of technology to harass, intimidate, tease, threaten, abuse or otherwise terrorise peers, teachers and/or the school in general, is discussed from both the psychological perspective and in terms of its legal ramifications (both criminal and civil) in Australia. Some recommendations for proactive and preventative measures, education and policy adoptions are provided, together with general advice to parents, schools and adolescents on awareness of the risks involved and how young people might better protect themselves in light of that knowledge.

Script proposals: a device for empowering clients in counselling

Much of the research on the delivery of advice by professionals such as physicians, health workers and counsellors, both on the telephone and in face to face interaction more generally, has focused on the theme of client resistance and the consequent need for professionals to adopt particular formats to assist in the uptake of the advice. In this paper we consider one setting, Kid’s Helpline, the national Australian counselling service for children and young people, where there is an institutional mandate not to give explicit advice in accordance with the values of self-direction and empowerment. The paper examines one practice, the use of script proposals by counsellors, which appears to offer a way of providing support which is consistent with these values. Script proposals entail the counsellors packaging their advice as something that the caller might say – at some future time – to a third party such as a friend, teacher, parent, or partner, and involve the counsellor adopting the speaking position of the caller in what appears as a rehearsal of a forthcoming strip of interaction. Although the core feature of a script proposal is the counsellor’s use of direct reported speech they appear to be delivered, not so much as exact words to be followed, but as the type of conversation that the client needs to have with the 3rd party. Script proposals, in short, provide models of what to say as well as alluding to how these could be emulated by the client. In their design script proposals invariably incorporate one or more of the most common rhetorical formats for maximising the persuasive force of an utterance such as a three part list or a contrastive pair. Script proposals, moreover, stand in a complex relation to the prior talk and one of their functions appears to be to summarise, respecify or expand upon the client’s own ideas or suggestions for problem solving that have emerged in these preceding sequences.