The cancer stem-cell hypothesis : its emerging role in lung cancer biology and its relevance for future therapy

The cancer stem-cell (CSC) hypothesis suggests that there is a small subset of cancer cells that are responsible for tumor initiation and growth, possessing properties such as indefinite self-renewal, slow replication, intrinsic resistance to chemotherapy and radiotherapy, and an ability to give rise to differentiated progeny. Through the use of xenotransplantation assays, putative CSCs have been identified in many cancers, often identified by markers usually expressed in normal stem cells. This is also the case in lung cancer, and the accumulated data on side population cells, CD133, CD166, CD44 and ALDH1 are beginning to clarify the true phenotype of the lung cancer stem cell. Furthermore, it is now clear that many of the pathways of normal stem cells, which guide cellular proliferation, differentiation, and apoptosis are also prominent in CSCs; the Hedgehog (Hh), Notch, and Wnt signaling pathways being notable examples. The CSC hypothesis suggests that there is a small reservoir of cells within the tumor, which are resistant to many standard therapies, and can give rise to new tumors in the form of metastases or relapses after apparent tumor regression. Therapeutic interventions that target CSC pathways are still in their infancy and clinical data of their efficacy remain limited. However Smoothened inhibitors, gamma-secretase inhibitors, anti-DLL4 antagonists, Wnt antagonists, and CBP/β-catenin inhibitors have all shown promising anticancer effects in early studies. The evidence to support the emerging picture of a lung cancer CSC phenotype and the development of novel therapeutic strategies to target CSCs are described in this review.

Engineering across cultures : new learning resources for intercultural competency in engineering

BACKGROUND The work described in this paper has emerged from an ALTC/OLT funded project, Exploring Intercultural Competency in Engineering. The project indentified many facets of culture and intercultural competence that go beyond a culture-as-nationality paradigm. It was clear from this work that resources were needed to help engineering educators introduce students to the complex issues of culture as they relate to engineering practice. A set of learning modules focussing on intercultural competence in engineering practice were developed early on in the project. Through the OLT project, these modules have been expanded into a range of resources covering various aspects of culture in engineering. Supporting the resources, an eBook detailing the ins and outs of intercultural competency has also been developed to assist engineering educators to embed opportunities for students to develop skills in unpacking and managing cross-cultural challenges in engineering practice. PURPOSE This paper describes the key principles behind the development of the learning modules, the areas they cover and the eBook developed to support the modules. The paper is intended as an introduction to the approaches and resources and extends an invitation to the community to draw from, and contribute to this initial work. DESIGN/METHOD A key aim of this project was to go beyond the culture-as-nationality approach adopted in much of the work around intercultural competency (Deardorff, 2011). The eBook explores different dimensions of culture such as workplace culture, culture’s influence on engineering design, and culture in the classroom. The authors describe how these connect to industry practice and explore what they mean for engineering education. The packaged learning modules described here have been developed as a matrix of approaches moving from familiar known methods through complicated activities relying to some extent on expert knowledge. Some modules draw on the concept of ‘complex un-order’ as described in the ‘Cynefin domains’ proposed by Kurtz and Snowden (2003). RESULTS Several of the modules included in the eBook have already been trialled at a variety of institutions. Feedback from staff has been reassuringly positive so far. Further trials are planned for second semester 2012, and version 1 of the eBook and learning modules, Engineering Across Cultures, is due to be released in late October 2012. CONCLUSIONS The Engineering Across Cultures eBook and learning modules provide a useful and ready to employ resource to help educators tackle the complex issue of intercultural competency in engineering education. The book is by no means exhaustive, and nor are the modules, they instead provide an accessible, engineering specific guide to bringing cultural issues into the engineering classroom.

Organotypic culture of normal, dysplastic and squamous cell carcinoma-derived oral cell lines reveals loss of spatial regulation of CD44 and p75(NTR) in malignancy

Oral squamous cell carcinomas (OSCC) often arise from dysplastic lesions. The role of cancer stem cells in tumour initiation is widely accepted, yet the potential existence of pre-cancerous stem cells in dysplastic tissue has received little attention. Cell lines from oral diseases ranging in severity from dysplasia to malignancy provide opportunity to investigate the involvement of stem cells in malignant progression from dysplasia. Stem cells are functionally defined by their ability to generate hierarchical tissue structures in consortium with spatial regulation. Organotypic cultures readily display tissue hierarchy in vitro; hence, in this study, we compared hierarchical expression of stem cell-associated markers in dermis-based organotypic cultures of oral epithelial cells from normal tissue (OKF6-TERT2), mild dysplasia (DOK), severe dysplasia (POE-9n) and OSCC (PE/CA P J15). Expression of CD44, p75NTR, CD24 and ALDH was studied in monolayers by flow cytometry and in organotypic cultures by immunohistochemistry. Spatial regulation of CD44 and p75NTR was evident for organotypic cultures of normal (OKF6-TERT2) and dysplasia (DOK and POE-9n) but was lacking for OSCC (PE/CA PJ15)-derived cells. Spatial regulation of CD24 was not evident. All monolayer cultures exhibited CD44, p75NTR, CD24 antigens and ALDH activity (ALDEFLUOR® assay), with a trend towards loss of population heterogeneity that mirrored disease severity. In monolayer, increased FOXA1 and decreased FOXA2 expression correlated with disease severity, but OCT3/4, Sox2 and NANOG did not. We conclude that dermis-based organotypic cultures give opportunity to investigate the mechanisms that underlie loss of spatial regulation of stem cell markers seen with OSCC-derived cells.

Using the Depression Anxiety Stress Scale 21 (DASS-21) across cultures

DASS-21 has been validated in a number of populations such as Hispanic adults, American, British and Australian. The findings show that the DASS-21 is psychometrically sound with good reliability and validity. It is clear from the literature that the DASS-21 is a well established instrument for measuring depression, anxiety and stress in the Western world. Nonetheless, the lack of appropriate validation amongst Asian populations continues to pose concerns over the use of DASS-21 in Asian samples. Cultural variation may influence the individual’s experience and emotional expression. Thus, when researchers and practitioners employ Western-based assessments with Asian populations by directly translating them without an appropriate validation, the process can be challenging. In summary, we have conducted a series of rigorous statistical tests and minimised any potential confounds from the demographic information. The advantages of this revised DASS-18 stress scale are twofold. First, the revised DASS-18 stress scale possessed fewer items, which resulted in a cleaner factorial structure. Second, it also had a smaller inter-factor correlation. With these justifications, the revised DASS-18 stress scale is potentially more suitable for the Asian populations.

Systematics and biology of the iconic Australian scribbly gum moths Ogmograptis Meyrick (Lepidoptera: Bucculatricidae) and their unique insect-plant interaction

The larvae of particular Ogmograptis spp. produce distinctive scribbles on some smooth-barked Eucalyptus spp. which are a common feature on many ornamental and forest trees in Australia. However, although they are conspicuous in the environment the systematics and biology of the genus has been poorly studied. This has been addressed through detailed field and laboratory studies of their biology of three species (O. racemosa Horak sp. nov., O. fraxinoides Horak sp. nov., O. scribula Meyrick), in conjunction with a comprehensive taxonomic revision support by a molecular phylogeny utilising the mitochondrial Cox1 and nuclear 18S genes. In brief, eggs are laid in bark depressions and the first instar larvae bore into the bark to the level where the future cork cambium forms (the phellegen). Early instar larvae bore wide, arcing tracks in this layer before forming a tighter zig-zag shaped pattern. The second last instar turns and bores either closely parallel to the initial mine or doubles its width, along the zig-zag shaped mine. The final instar possesses legs and a spinneret (unlike the earlier instars) and feeds exclusively on callus tissue which forms within the zig-zag shaped mine formed by the previous instar, before emerging from the bark to pupate at the base of the tree. The scars of mines them become visible scribble following the shedding of bark. Sequence data confirm the placement of Ogmograptis within the Bucculatricidae, suggest that the larvae responsible for the ‘ghost scribbles’ (unpigmented, raised scars found on smooth-barked eucalypts) are members of the genus Tritymba, and support the morphology-based species groups proposed for Ogmograptis. The formerly monotypic genus Ogmograptis Meyrick is revised and divided into three species groups. Eleven new species are described: Ogmograptis fraxinoides Horak sp. nov., Ogmograptis racemosa Horak sp. nov. and Ogmograptis pilularis Horak sp. nov. forming the scribula group with Ogmograptis scribula Meyrick; Ogmograptis maxdayi Horak sp. nov., Ogmograptis barloworum Horak sp. nov., Ogmograptis paucidentatus Horak sp. nov., Ogmograptis rodens Horak sp. nov., Ogmograptis bignathifer Horak sp. nov. and Ogmograptis inornatus Horak sp. nov. as the maxdayi group; Ogmograptis bipunctatus Horak sp. nov., Ogmograptis pulcher Horak sp. nov., Ogmograptis triradiata (Turner) comb. nov. and Ogmograptis centrospila (Turner) comb. nov. as the triradiata group. Ogmograptis notosema (Meyrick) cannot be assigned to a species group as the holotype has not been located. Three unique synapomorphies, all derived from immatures, redefine the family Bucculatricidae, uniting Ogmograptis, Tritymba Meyrick (both Australian) and Leucoedemia Scoble & Scholtz (African) with Bucculatrix Zeller, which is the sister group of the southern hemisphere genera. The systematic history of Ogmograptis and the Bucculatricidae is discussed.

Blood cultures for evaluation of early postoperative fever after femoral neck fracture surgery

PURPOSE. To evaluate the utility of blood cultures in the assessment of early postoperative fever in hip fracture patients with no other indicators of sepsis. METHODS. 101 blood cultures were drawn on postoperative days 0 to 5 to investigate 84 febrile episodes in 31 women and 30 men (mean age, 80 years) whose body temperature measured via the tympanic route was ≥38ºC. Culture results of these 61 patients were divided into culture-positive and culture-negative groups for comparison. RESULTS. Of the 101 blood cultures, only 2 were positive: one was obtained 5 days after dynamic hip screw fixation, and the other 4 days after hemiarthroplasty. Both blood cultures grew coagulase-negative staphylococcal species, which were deemed to be skin contaminants not requiring change of patient management. 44 of these patients were treated with oral or intravenous antibiotics for a period of time. CONCLUSION. The risk of bacteraemia in patients with postoperative fever but no other symptoms of infection is low. Routine procurement of blood cultures in such patients is ineffective and of limited utility.

Ingenious : Emerging Youth Cultures in Urban Australia

The book documents new findings on the contribution of migrant young people to Australia’s urban life. The essays collected traces teenagers within a world of city suburbs and P plates, shopping malls and chat rooms and text messages. Proud of their migrant backgrounds, they are moving away from explicit ethnically defined cultural groups to focus on their place in contemporary Australian society. These young people through their every day activities are redefining what it means to be an Australian The book is edited by widely published cultural researchers Melissa Butcher from the University of Sydney and Mandy Thomas from the Australian National University who together worked on the GENERATE project. It is far too common for our youth to be portrayed as not belonging to our dominant or mainstream culture. In Ingenious, the editors study the kaleidoscope of influences and environments our youth move within - online networks, dance parties and more - to paint a flexible, innovative generation.

Intercultural dance : exploring a Finnish migrant connection with indigenous cultures through dance

This research is a dance-based, autoethnographic study which explores my connection with place as a Savolainen woman born on Kalkadoon country; an Australian-born Finn. Edward Relph states 'the more profoundly inside a place the person feels, the stronger will be his or her identity with that place' (1976, 49). I am interested in how a sense of "place identity" has informed my choreographic practice. Autoethnography is important because it places the research within a lived experience: my insider account of a lived experience within the White Australia Policy through my lens as a first generation Australian-born Finn. It also speaks to the space in-between for those, like me, who feel they do not fit into mainstream identity but look like they do. By exploring my lived experience through dance autoethnography, new understandings of my place identity within a cultural, social and political context have emerged. Ellis and Flaherty state ‘subjectivity is situated such that the voices in our heads and the feelings in our bodies are linked to political, cultural, and historical contexts’ (1992, 4). In order to begin my rehearsal process, I wanted a cultural framework which related to connection with land to guide the research. My investigations led me to the Maori examples of "Tikanga Maori" (Tikanga are the customs and traditions), in particular the "Pepeha" (Introduction) and allowed me to challenge my choreographic practice through this cultural framework.

Vision, Viability and Value: Three perspectives on the performing arts across cultures, context and nations

How can we reach out to institutions, artists and audiences with sometimes radically different agendas to encourage them to see, participate in and support the development of new practices and programs in the performing arts? In this paper, based on a plenary panel at PSi#18 Performance Culture Industry at the University of Leeds, Clarissa Ruiz (Columbia), AnuradhaKapur (India) and Sheena Wrigley (England) together with interloctorBree Hadley (Australia) speak about their work in as policy-makers, managers and producers in the performing arts in Europe, Asia and America over the past several decades. Acknowledged trailblazers in their fields, Ruiz, Kapur and Wrigley all have a commitment to creating a vital, viable and sustainable performing arts ecologies. Each has extensive experience in performance, politics, and the challenging process of managing histories, visions, stakeholders, and sometimes scarce resources to generate lasting benefits for the various communities have worked for, with and within. Their work, cultivating new initiatives, programs or policy has made them expert at brokering relationships in and in between private, public and political spheres to elevate the status of and support for performing arts as a socially and economically beneficial activity everyone can participate in. Each gives examples from their own practice to provide insight into how to negotiate the interests of artistic, government, corporate, community and education partners, and the interests of audiences, to create aesthetic, cultural and / or economic value. Together, their views offer a compelling set of perspectives on the changing meanings of the ‘value of the arts’ and the effects this has had for the artists that make and arts organisations that produce and present work in a range of different regional, national and cross-national contexts.

In vitro functional characterisation of IGF-I : VN-induced breast cancer progression

Members of the insulin-like growth factor (IGF) family have been shown to play critical roles in normal growth and development, as well as in tumour biology. The IGF system is complex and the biological effects of the IGFs are determined by their diverse interactions between many molecules, including their interactions with extracellular matrix (ECM) proteins. Recent studies have demonstrated that IGFs associate with the ECM protein vitronectin (VN) through IGF-binding proteins (IGFBP) and that this interaction modulates IGF-stimulated biological functions, namely cell migration and cell survival through the cooperative involvement of the type-I IGF receptor (IGF-1R) and VN-binding integrins. Since IGFs play important roles in the transformation and progression of breast cancer and VN has been found to be over-expressed at the leading edge of breast tumours, this project aimed to describe the effects of IGF-I:VN interactions on breast cell function. This was undertaken to dissect the molecular mechanisms underlying IGF-I:VN-induced responses and to design inhibitors to block the effects of such interactions. The studies described herein demonstrate that the increase in migration of MCF-7 breast cancer cells in response to the IGF-I:IGFBP-5:VN complex is accompanied by differential expression of genes known to be involved in migration, invasion and/or survival, including Tissue-factor (TF), Stratifin (SFN), Ephrin-B2, Sharp-2 and PAI-1. This „migration gene signature‟ was confirmed using real-time PCR analysis. Substitution of the native IGF-I within the IGF-I:IGFBP:VN complex with the IGF-I analogue, \[L24]\[A31]-IGF-I, which has a reduced affinity for the IGF-1R, failed to stimulate cell migration and interestingly, also failed to induce the differential gene expression. This supports the involvement of the IGF-1R in mediating these changes in gene expression. Furthermore, lentiviral shRNA-mediated stable knockdown of TF and SFN completely abrogated the increased cell migration induced by IGF-I:IGFBP:VN complexes in MCF-7 cells. Indeed, when these cells were grown in 3D Matrigel™ cultures a decrease in the overall size of the 3D spheroids in response to the IGF-I:IGFBP:VN complexes was observed compared to the parental MCF-7 cells. This suggests that TF and SFN have a role in complex-stimulated cell survival. Moreover, signalling studies performed on cells with the reduced expression of either TF or SFN had a decreased IGF-1R activation, suggesting the involvement of signalling pathways downstream of IGF-1R in TF- and/or SFN-mediated cell migration and cell survival. Taken together, these studies provide evidence for a common mechanism activated downstream of the IGF-1R that induces the expression of the „migration gene signature‟ in response to the IGF-I:IGFBP:VN complex that confers breast cancer cells the propensity to migrate and survive. Given the functional significance of the interdependence of ECM and growth factor (GF) interactions in stimulating processes key to breast cancer progression, this project aimed at developing strategies to prevent such growth factor:ECM interactions in an effort to inhibit the downstream functional effects. This may result in the reduction in the levels of ECM-bound IGF-I present in close proximity to the cells, thereby leading to a reduction in the stimulation of IGF-1R present on the cell surface. Indeed, the inhibition of IGF-I-mediated effects through the disruption of its association with ECM would not alter the physiological levels of IGF-I and potentially only exert effects in situations where abnormal over expression of ECM proteins are found; namely carcinomas and hyperproliferative diseases. In summary, this PhD project has identified novel, innovative and realistic strategies that can be used in vitro to inhibit the functions exerted by the IGF-I:IGFBP:VN multiprotein complexes critical for cancer progression, with a potential to be translated into in vivo investigations. Furthermore, TF and SFN were found to mediate IGF-I:IGFBP:VN-induced effects, thereby revealing their potential to be used as therapeutic targets or as predictive biomarkers for the efficacy of IGF-1R targeting therapies in breast cancer patients. In addition to its therapeutic and clinical scope, this PhD project has significantly contributed to the understanding of the role of the IGF system in breast tumour biology by providing valuable new information on the mechanistic events underpinning IGF-I:VN-mediated effects on breast cell functions. Furthermore, this is the first instance where favourable binding sites for IGF-II, IGFBP-3 and IGFBP-5 on VN have been identified. Taken together, this study has functionally characterised the interactions between IGF-I and VN and through innovative strategies has provided a platform for the development of novel therapies targeting these interactions and their downstream effects.

Re-orientations : East Asian popular cultures in contemporary Vietnam

Vietnamese-Australians live in Australia, a large island continent. The physical contrast between Vietnam and Australia is remarked upon by many Vietnamese in their migration stories. Whereas Vietnam is remembered as an interlinked sensual and social world, Australia is often viewed as a harsh, spacious, empty, dry continent. Australia is located in a regional Asian context, but this location has always been culturally and politically problematic, as it historically attempted to define itself as a "white" European nation in the Southern Hemisphere (Ang, 2000, p. xiii; McNamara & Coughlan, 1997, p. 1). During the Gold Rush period in the late 1800s, when there was widespread opposition to Chinese labor, Australia implemented a "White Australia" policy, although there were historically a significant number of Australians of Asian background. This exclusionary immigration policy was effectively overturned in the 1970s with the acceptance of a large number of refugees from Vietnam, Cambodia, and Laos in 1975. Vietnamese-Australians live predominantly in urban areas with over three quarters living in Sydney and Melbourne, the two largest cities. Within these two cities they are also highly concentrated in ethnically diverse suburbs, most living in areas with more than 1,000 residents born in Vietnam (Viviani, 1996, p. 49). However, Jupp (Jupp et al., 1990; Jupp, 1993) has argued that these areas are also zones of transition, with much movement in and out.

Development and validation of an instrument to measure organizational cultures' support of business process management

The purpose of Business Process Management (BPM) is to increase the efficiency and effectiveness of organizational processes through improvement and innovation. Despite a common understanding that culture is an important element in these efforts, there is a dearth of theoretical and empirical research on culture as a facilitator of successful BPM. We develop the BPM culture construct and propose a validated instrument with which to measure organizational cultures’ support of BPM. The operationalization of the BPM culture concept provides a theoretical foundation for future research and a tool to assist organizations in developing a cultural environment that supports successful BPM.