Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer

Purpose The role played by the innate immune system in determining survival from non-small-cell lung cancer (NSCLC) is unclear. The aim of this study was to investigate the prognostic significance of macrophage and mast-cell infiltration in NSCLC. Methods We used immunohistochemistry to identify tryptase+ mast cells and CD68+ macrophages in the tumor stroma and tumor islets in 175 patients with surgically resected NSCLC. Results Macrophages were detected in both the tumor stroma and islets in all patients. Mast cells were detected in the stroma and islets in 99.4% and 68.5% of patients, respectively. Using multivariate Cox proportional hazards analysis, increasing tumor islet macrophage density (P < .001) and tumor islet/stromal macrophage ratio (P < .001) emerged as favorable independent prognostic indicators. In contrast, increasing stromal macrophage density was an independent predictor of reduced survival (P = .001). The presence of tumor islet mast cells (P = .018) and increasing islet/stromal mast-cell ratio (P = .032) were also favorable independent prognostic indicators. Macrophage islet density showed the strongest effect: 5-year survival was 52.9% in patients with an islet macrophage density greater than the median versus 7.7% when less than the median (P < .0001). In the same groups, respectively, median survival was 2,244 versus 334 days (P < .0001). Patients with a high islet macrophage density but incomplete resection survived markedly longer than patients with a low islet macrophage density but complete resection. Conclusion The tumor islet CD68+ macrophage density is a powerful independent predictor of survival from surgically resected NSCLC. The biologic explanation for this and its implications for the use of adjunctive treatment requires further study. © 2005 by American Society of Clinical Oncology.

Contribution of fibroblast and mast cell (afferent) and tumor (efferent) IL-6 effects within the tumor microenvironment

Hyperactive inflammatory responses following cancer initiation have led to cancer being described as a 'wound that never heals'. These inflammatory responses elicit signals via NFκB leading to IL-6 production, and IL-6 in turn has been shown to induce epithelial to mesenchymal transition in breast cancer cells in vitro, implicating a role for this cytokine in cancer cell invasion. We previously have shown that conditioned medium derived from cancer-associated fibroblasts induced an Epithelial to Mesenchymal transition (EMT) in PMC42-LA breast cancer cells and we have now identify IL-6 as present in this medium. We further show that IL-6 is expressed approximately 100 fold higher in a cancer-associated fibroblast line compared to normal fibroblasts. Comparison of mouse-specific (stroma) and human-specific (tumor) IL-6 mRNA expression from MCF-7, MDA MB 468 and MDA MB 231 xenografts also indicated the stroma rather than tumor as a significantly higher source of IL-6 expression. Mast cells (MCs) feature in inflammatory cancer-associated stroma, and activated MCs secrete IL-6. We observed a higher MC index (average number of mast cells per xenograft section/average tumor size) in MDA MB 468 compared to MDA MB 231 xenografts, where all MC were observed to be active (degranulating). This higher MC index correlated with greater mouse-specific IL-6 expression in the MDA MB 468 xenografts, implicating MC as an important source of stromal IL-6. Furthermore, immunohistochemistry on these xenografts for pSTAT3, which lies downstream of the IL-6 receptor indicated frequent correlations between pSTAT3 and mast cell positive cells. Analysis of publically available databases for IL-6 expression in patient tissue revealed higher IL-6 in laser capture microdissected stroma compared to adjacent tissue epithelium from patients with inflammatory breast cancer (IBC) and invasive non-inflammatory breast cancer (non-IBC) and we show that IL-6 expression was significantly higher in Basal versus Luminal molecular/phenotypic groupings of breast cancer cell lines. Finally, we discuss how afferent and efferent IL-6 pathways may participate in a positive feedback cycle to dictate tumor progression.

The role of IL-17-secreting mast cells in inflammatory joint disease

The proinflammatory cytokine IL-17 has an important role in pathogenesis of several inflammatory diseases. In immune-mediated joint diseases, IL-17 can induce secretion of other proinflammatory cytokines such as IL-1, IL-6 and TNF, as well as matrix metalloproteinase enzymes, leading to inflammation, cartilage breakdown, osteoclastogenesis and bone erosion. In animal models of inflammatory arthritis, mice deficient in IL-17 are less susceptible to development of disease. The list of IL-17-secreting cells is rapidly growing, and mast cells have been suggested to be a dominant source of IL-17 in inflammatory joint disease. However, many other innate sources of IL-17 have been described in both inflammatory and autoinflammatory conditions, raising questions as to the role of mast cells in orchestrating joint inflammation. This article will critically assess the contribution of mast cells and other cell types to IL-17 production in the inflammatory milieu associated with inflammatory arthritis, understanding of which could facilitate targeted therapeutic approaches. © 2013 Macmillan Publishers Limited. All rights reserved.

Defining friendworks : communication perspective on social networks types

This paper introduces friendwork as a new term in social networks studies. A friendwork is a network of friends. It is a specific case of an interpersonal social network. Naming this seemingly well known and familiar group of people as a friendwork facilitates its differentiation from the overall social network, while highlighting this subgroup's specific attributes and dynamics. The focus on one segment within social networks stimulates a wider discussion regarding the different subgroups within social networks. Other subgroups also discussed in this paper are: family dependent, work related, location based and virtual acquaintances networks. This discussion informs a larger study of social media, specifically addressing interactive communication modes that are in use within friendworks: direct (face-to-face) and mediated (mainly fixed telephone, internet and mobile phone). It explores the role of social media within friendworks while providing a communication perspective on social networks.

Australian horror movies

The Australian horror film is a fascinating specimen. While a tradition has antecedents in the silent era of cinema, and at times has produced popular and commercially successful titles, Australian horror films have existed among the shadows of Australian cinema. Within a national cinema funded by public subsidy to foster a sense of national identity, emphasizing ‘quality’ cultural films and refusing to recognize popular movie genres in attempt to differentiate itself from Hollywood, generic and low-culture horror films have been in opposition to these objectives. Consequently, horror movies have been heavily marginalized within public funding environments and mainstream film culture, and either ignored or despised by mainstream critics. The chapter provides a historical introduction to Australian horror cinema before reviewing a selection of recent Aussie horror titles, namely: Wolf Creek, Undead, Black Water, Dying Breed, Lost Things, Prey, Cut, Rogue and Storm Warning.

Remote interaction and user research : anaesthetic preadmission activity

In the absence of telehealth technology, rural patients must travel to a regional or metropolitan hospital for a preadmission consultation one week before their surgery. Currently, examination of the patient’s chest using a stethoscope (auscultation) is not possible over a telehealth network as existing digital stethoscopes have been designed for in-person auscultation. We report on the initial phase of research which ultimately aims to design a digital stethoscope for use in the telehealth context. This initial research phase describes the complexity of the activity of preadmission clinics and the implications for the design of the stethoscope. The research is conducted through field studies of existing face-to-face and remote consultations.

Passenger experience in an airport : an activity-centred approach

An airport is one of the largest and most complex systems in modern society. Observational field studies have been conducted to investigate passenger experiences in, and interactions within, an international airport. Based on these studies, this paper discusses how activities mediate people’s experiences in the airport. For example, moving through the security screening process is discussed from both passenger and staff perspectives. The applied coding scheme ensured research rigor. The findings illustrate that passenger activities are complex and shared, and only partially supported by current terminal design. Thus, this research has the potential to impact on airport design to facilitate passenger flow through airport precincts.

Passengers in the airport : artefacts and activities

This study addresses the ordinary activities of passengers in airports. Using observational techniques we investigated how passenger activities are mediated by artefacts, in this the bags that people carry. The relationship between passengers and their bags is shown to be complex and contingent on many factors. We report on our early research in the airport and document an emerging taxonomy of passenger activity. The significance of this research is in the contribution made to an understanding of passenger activities which could contribute to the design of future technologies for passenger facilitation and to airport terminal design.

Contrasting scenarios : embracing speech recognition

The purpose of this chapter is to describe the use of caricatured contrasting scenarios (Bødker, 2000) and how they can be used to consider potential designs for disruptive technologies. The disruptive technology in this case is Automatic Speech Recognition (ASR) software in workplace settings. The particular workplace is the Magistrates Court of the Australian Capital Territory.----- Caricatured contrasting scenarios are ideally suited to exploring how ASR might be implemented in a particular setting because they allow potential implementations to be “sketched” quickly and with little effort. This sketching of potential interactions and the emphasis of both positive and negative outcomes allows the benefits and pitfalls of design decisions to become apparent.----- A brief description of the Court is given, describing the reasons for choosing the Court for this case study. The work of the Court is framed as taking place in two modes: Front of house, where the courtroom itself is, and backstage, where documents are processed and the business of the court is recorded and encoded into various systems.----- Caricatured contrasting scenarios describing the introduction of ASR to the front of house are presented and then analysed. These scenarios show that the introduction of ASR to the court would be highly problematic.----- The final section describes how ASR could be re-imagined in order to make it useful for the court. A final scenario is presented that describes how this re-imagined ASR could be integrated into both the front of house and backstage of the court in a way that could strengthen both processes.

The vernacular terrain : Songzhang Art Museum, Beijing, China

The field was the curation of cross-cultural new media/ digital media practices within large-scale exhibition practices in China. The context was improved understandings of the intertwining of the natural and the artificial with respect to landscape and culture, and their consequent effect on our contemporary globalised society. The research highlighted new languages of media art with respect to landscape and their particular underpinning dialects. The methodology was principally practice-led. --------- The research brought together over 60 practitioners from both local and diasporic Asian, European and Australian cultures for the first time within a Chinese exhibition context. Through pursuing a strong response to both cultural displacement and re-identification the research forged and documented an enduring commonality within difference – an agenda further concentrated through sensitivities surrounding that year’s Beijing’s Olympics. In contrast to the severe threats posed to the local dialects of many of the world’s spoken and written languages the ‘Vernacular Terrain’ project evidenced that many local creative ‘dialects’ of the environment-media art continuum had indeed survived and flourished. --------- The project was co-funded by the Beijing Film Academy, QUT Precincts, IDAProjects and Platform China Art Institute. A broad range of peer-reviewed grants was won including from the Australia China Council and the Australian Embassy in China. Through invitations from external curators much of the work then traveled to other venues including the Block Gallery at QUT and the outdoor screens at Federation Square, Melbourne. The Vernacular Terrain catalogue featured a comprehensive history of the IDA project from 2000 to 2008 alongside several major essays. Due to the reputation IDA Projects had established, the team were invited to curate a major exhibition showcasing fifty new media artists: The Vernacular Terrain, at the prestigious Songzhang Art Museum, Beijing in Dec 07-Jan 2008. The exhibition was designed for an extensive, newly opened gallery owned by one of China's most important art historians Li Xian Ting. This exhibition was not only this gallery’s inaugural non-Chinese curated show but also the Gallery’s first new media exhibition. It included important works by artists such as Peter Greenway, Michael Roulier, Maleonn and Cui Xuiwen. --------- Each artist was chosen both for a focus upon their own local environmental concerns as well as their specific forms of practice - that included virtual world design, interactive design, video art, real time and manipulated multiplayer gaming platforms and web 2.0 practices. This exhibition examined the interconnectivities of cultural dialogue on both a micro and macro scale; incorporating the local and the global, through display methods and design approaches that stitched these diverse practices into a spatial map of meanings and conversations. By examining the contexts of each artist’s practice in relationship to the specificity of their own local place and prevailing global contexts the exhibition sought to uncover a global vernacular. Through pursuing this concentrated anthropological direction the research identified key themes and concerns of a contextual language that was clearly underpinned by distinctive local ‘dialects’ thereby contributing to a profound sense of cross-cultural association. Through augmentation of existing discourse the exhibition confirmed the enduring relevance and influence of both localized and globalised languages of the landscape-technology continuum.