MMP-9 and the epidermal growth factor signal pathway in non-small cell lung cancer

Background Matrix metalloproteinase (MMP)-9 is an endopeptidase that digests basement membrane type-IV collagen. Enhanced expression has been related to tumour progression in a number of systems. The control of MMP expression is complex, but recently epidermal growth actor receptor (EGFR) activity has been implicated in up-regulation of MMP-9 in tumour cells in vitro. Aims To evaluate interrelations between MMP-9 and EGFR expression in non-small cell lung cancer (NSCLC) and to assess the impact of expression on survival. Methods This is a retrospective study of 152 patients who underwent resection for stage I-IIIa NSCLC with a post-operative survival >60 days. Minimum follow-up was 2 years. Standard ABC immunohistochemistry was performed on 4μm paraffin-embedded sections from the tumour periphery using monoclonal antibodies to MMP-9 and EGFR. Results: MMP-9 was expressed in the tumour cells of 79/152 (52%) cases. EGFR expression was found in 86/152 (57%) cases [membranous 51/152 (34%), cytoplasmic 35/152 (23%)]. MMP-9 expression was associated with poor outcome (p=0.04). Membranous, cytoplasmic and overall EGFR expression were not associated with outcome (p=0.29, p=0.85 and p=0.41 respectively). There was a strong correlation between MMP-9 expression and EGFR expression (p=0.001) and EGFR membranous expression (p=0.01) but not with cytoplasmic EGFR expression (p=0.28). Co-expression of MMP-9 and EGFR (36%) conferred a worse prognosis (p=0.003). Subset analysis revealed only MMP-9 and membranous EGFR co-expression (22%) was associated with poor outcome (p=0.008). Conclusions Our results show that MMP-9 and EGFR are co-expressed in NSCLC. This finding suggests the EGFR signalling pathway may play an important role in the invasive behaviour of NSCLC via specific upregulation of MMP-9. The co-expression of these markers also confers a poor prognosis.

Expression and prognostic influence of MMP-2, MMP-9 and TIMP-2 in non-small cell lung cancer

Background Matrix metalloproteinases (MMPs) are a family of endopeptidases that digest the extracellular matrix (ECM). Overexpression of different MMPs has been shown to promote tumour cell invasion in vitro. Tissue inhibitors of matrix metalloproteinases (TIMPs) are specific inhibitors of MMPs that also possess growth-promoting properties. Aims To analyse the expression profile of MMP-2, MMP-9 and TIMP-2 in non-small cell lung cancer (NSCLC) and to assess the impact of expression on survival. Methods This is a retrospective study of patients who underwent resection for stage I-IIIa NSCLC with a post-operative survival >60 days. Patient follow up was a minimum of 2 years. Standard ABC immunohistochemistry was performed on 4μm paraffin-embedded sections from the tumour periphery using monoclonal antibodies to MMP-2, MMP-9 and TIMP-2. Results The results of the immunohistochemistry are set out below. marker tumour expression log-rank survival stromal expression log-rank survival MMP-2 9/72 (13%) p=0.10 34/72 (47%) p=0.34 MMP-9 79/152 (52%) p=0.04* 69/152 (45%) p=0.84 TIMP-2 28/90 (31%) p=0.04* 66/90 (73%) p=0.90 Two or more 16/59 (27%) p=0.007* There were no associations between expression and clinicopathological findings for any tumour marker. There was co-expression of MMP-2 and MMP-9 in tumour cells (p=0.01). Conclusions MMP-2, MMP-9 and TIMP-2 are expressed in NSCLC. MMP-9 and TIMP-2 tumour expression correlate with a poor outcome (both p=0.04) and are potential prognostic markers for NSCLC. Cumulative expression of two or more MMPs/TIMPs may also have increased prognostic significance. Proteases and their inhibitors are novel targets for therapeutic intervention and should be evaluated in NSCLC.

Prognostic significance of platelet and microvessel counts in operable non-small cell lung cancer

Background: Microvessel density, an indirect measure of angiogenesis, has been shown to be an independent prognostic marker in many solid tumours including non-small cell lung cancer (NSCLC). Platelets transport and release angiogenic growth factors. Platelets are increasingly likely to adhere to tumour microvessels due to raised expression of platelet-binding proteins and stasis in blood-flow. Increased vascular permeability in tumour microvessels facilitates platelet extravasation into the extracellular matrix. Adherence and extravasation both lead to platelet activation and release of growth factors capable of instigating the angiogenic process. Methods: A total of 181 patients were identified who underwent resection of stage I-IIIa NSCLC with a post-operative survival >60 days. Patients were followed-up for a minimum of 24 months. Sections from the tumour periphery were stained for the endothelial marker CD34 (Novocastra NCL-END) using standard ABC immunohistochemistry. Chalkley counting was used to assess microvessel density. Results: A pre-operative platelet count greater than the median and above the normal range (>400) was associated with a poor outcome (P = 0.01 and P = 0.04, respectively). Tumours with an above median and high Chalkley count (upper tertile) had a worse prognosis (P = 0.007 and P = 0.0006, respectively). There was no association between platelet count and Chalkley count. Conclusions: Platelet and microvessel counts are both potential prognostic markers for NSCLC. The role of platelets in the angiogenic process needs to be further investigated. (C) 2000 Elsevier Science Ireland Ltd.

Flapless dental implant surgery : a retrospective study of 1,241 consecutive implants

Purpose: The purpose of this study was to identify retrospectively the predictors of implant survival when the flapless protocol was used in two private dental practices. Materials and Methods: The collected data were initially computer searched to identify the patients; later, a hand search of patient records was carried out to identify all flapless implants consecutively inserted over the last 10 years. The demographic information gathered on statistical predictors included age, sex, periodontal and peri-implantitis status, smoking, details of implants inserted, implant locations, placement time after extraction, use of simultaneous guided hard and soft tissue regeneration procedures, loading protocols, type of prosthesis, and treatment outcomes (implant survival and complications). Excluded were any implants that required flaps or simultaneous guided hard and soft tissue regeneration procedures, and implants narrower than 3.25 mm. Results: A total of 1,241 implants had been placed in 472 patients. Life table analysis indicated cumulative 5-year and 10-year implant survival rates of 97.9% and 96.5%, respectively. Most of the failed implants occurred in the posterior maxilla (54%) in type 4 bone (74.0%), and 55.0% of failed implants had been placed in smokers. Conclusion: Flapless dental implant surgery can yield an implant survival rate comparable to that reported in other studies using traditional flap techniques.

The role of chemotherapy in the treatment of adult soft tissue sarcomas

Adult soft tissue sarcomas are relatively rare tumours which are curable with radical surgery. Approximately 50% of patients will develop inoperable disease or metastases for which chemotherapy may be inappropriate. Only two cytotoxic agents - doxorubicin and ifosfamide - have activity in > 20% of patients. For both these agents there is evidence of a dose-response relationship. There is currently no good evidence that combination chemotherapy confers a clinical benefit compared with single agents. Outside a clinical trial, standard first-line therapy should be with single agent doxorubicin at a dose intensity ≥ 70 mg2 every 3 weeks. Approximately 25% of patients may be expected to respond to this regimen. There is the suggestion that responses may occur to ifosfamide in patients who progress on doxorubicin. The role of chemotherapy in the adjuvant setting remains uncertain. Several trials have suggested a modest relapse-free and overall survival benefit for the use of post-operative chemotherapy and a recent overview of 14 randomised trials confirms a small though significant benefit. These benefits have to be weighed against the toxicity of chemotherapy. The importance of treating all patients with soft tissue sarcomas in clinical trials is stressed. There is an urgent need to define new active agents to treat this disease.

Talking the talk : therapeutic jurisprudence and oral competence

In Australian criminal justice systems, a wide range of pathways to sentencing and punishment exist alongside traditional court processes. In particular, therapeutic jurisprudence ('TJ') processes have emerged during the last quarter of a century and now occupy a key position in the criminal justice landscape. This article provides an introduction to TJ, highlighting in particular the emphasis it places on the active participation of offenders, before critically discussing offenders' capacity to engage with TJ processes. The article then summarises the research on the oral competence of offenders, and argues that offenders who lack oral competence may be disadvantaged in TJ processes. Finally, we provide an overview of the limited guidance that has been provided to TJ practitioners on how to maximise the participation of offenders with limited oral competence.

Primary stability of two uncemented acetabular components of different geometry : hemispherical or peripherally enhanced?

Objective This study compared the primary stability of two commercially available acetabular components from the same manufacturer, which differ only in geometry; a hemispherical and a peripherally enhanced design (peripheral self-locking (PSL)). The objective was to determine whether altered geometry resulted in better primary stability. Methods Acetabular components were seated with 0.8 mm to 2 mm interference fits in reamed polyethylene bone substrate of two different densities (0.22 g/cm3 and 0.45 g/cm3). The primary stability of each component design was investigated by measuring the peak failure load during uniaxial pull-out and tangential lever-out tests. Results There was no statistically significant difference in seating force (p = 0.104) or primary stability (pull-out p = 0.171, lever-out p = 0.087) of the two components in the low-density substrate. Similarly, in the high-density substrate, there was no statistically significant difference in the peak pull-out force (p = 0.154) or lever-out moment (p = 0.574) between the designs. However, the PSL component required a significantly higher seating force thanthe hemispherical cup in the high-density bone analogue (p = 0.006). Conclusions Higher seating forces associated with the PSL design may result in inadequate seating and increased risk of component malpositioning or acetabular fracture in the intra-operative setting in high-density bone stock. Our results, if translated clinically, suggest that a purely hemispherical geometry may have an advantage over a peripherally enhanced geometry in high density bone stock.

Scared straight : boot camps for Queensland

The Liberal National Party (‘LNP’) ‘tough on youth crime’ policy mantra was well publicised in the months leading up to the 2012 Queensland state election. 1 Boot camp trials were espoused as a quick-fix panacea — a way of addressing youth offending. The idea was particularly favoured in the far northern regions of the state. In line with the new government’s policy, the Youth Justice (Boot Camp Orders) and Other Legislation Amendment Bill 2012 (Qld) (‘the Bill’) had a speedy passage through the unicameral Queensland parliament. It was introduced on 1 November 2012, scrutinised by the Legal Affairs and Community Safety Committee (‘LACSC’) which sought community feedback, and reported back to Parliament within the given timeframe of three weeks. The Bill received assent early December and the provisions commenced in January 2013. This article examines the legislative changes implemented in Queensland. It analyses the issues prompting the amendments such as the perception that parts of Queensland were in the grip of a ‘soaring juvenile crime rate’, the conservative government’s ‘tough stance’ policy towards youth offending, and the transfer of youth justice ‘solutions’ such as ‘boot camps’ among jurisdictions. The article assesses the evidence base for boot camp orders as an option in sentencing young offenders and concludes by raising serious concerns about pursuing such a narrow hardline approach to youth justice.

RANKL expression in periodontal disease : where does RANKL come from?

Periodontitis is an inflammatory disease characterized by periodontal pocket formation and alveolar bone resorption. Periodontal bone resorption is induced by osteoclasts and receptor activator of nuclear factor-κB ligand (RANKL) which is an essential and central regulator of osteoclast development and osteoclast function. Therefore, RANKL plays a critical role in periodontal bone resorption. In this review, we have summarized the sources of RANKL in periodontal disease and explored which factors may regulate RANKL expression in this disease.

WATER - a series of photographs by Louise Grayson

This body of photographic work has been created to firstly, explore a new approach to practice-led research that uses an “action genre” approach to reflective practice (Lemke) and secondly, to visually explore human interaction with the fundamental item in life - water. The first of these is based on the contention that to understand the meanings inherent in photographs we cannot look merely at the end result. It is essential to keep looking at the actions of practitioners, and the influences upon them, to determine how external influences affect the meaning potential of editorial photographs (Grayson, 2012). WATER therefore, provides an ideal platform to reflect upon the actions and influences involved in creating work within the photographic genre of photojournalism. It enables this practitioner to reflect on each stage of production to gain a better understanding of how external influences impact the narrative potential within images created. There are multi-faceted influences experienced by photographers who are creating images that, in turn, are part of constructing and presenting the narrative potential of editorial photographs. There is an important relationship between professional photographers and the technical, cultural, economic and institutional forces that impinge upon all stages of production and publication. What results is a greater understanding of technical, cultural, economic and institutional forces that impinge upon all stages of production and publication. Therefore, to understand the meanings inherent in photographs within WATER, I do not look merely at the end result. It provides a case study looking at my actions in the filed, and the influences upon me, to determine how external influences affect the meaning potential of these photographs (Grayson, 2012). As a result, this project adds to the body of scholarship around the definition of Photojournalism, how it has adapted to the current media environment and provides scope for further research into emerging new genres within editorial photography, such as citizen photojournalism. Concurrently, the photographs themselves were created to visually explore how there remains a humanistic desire to interact with the natural form of water even while living a modern cosmopolitan life around it. Taking a photojournalistic approach to exploring this phenomenon, the images were created by “capturing moments as they happened” with no posing or setting up of images. This serendipitous approach to the photographic medium provides the practitioner with at least an attempt to direct the subjectivity contained explicitly in photographs. What results is a series of images that extend the visual dialogue around the role of water within modern humanistic lifestyles and how it remains an integral part of our society’s behaviors. It captures important moments that document this relationship at this time of modern development. The resulting works were exhibited and published as part of the Head On Photo Festival, Australia's largest photo festival and the world's second largest festival in Sydney 20-24 May 2013. The WATER series of images were curated by three Magnum members; Ian Berry, Eli Reed and Chris Steele-Perkins. Magnum is a highly regarded international photographic co-operative with editorial offices in New York, London, Paris and Tokyo. There was a projection of the works as part of the official festival programme, presented to both members of the public and Sydney’s photography professionals. In addition, a sample of images from the WATER series was chosen for inclusion in the Magnum-published hardcover book. References Grayson, Louise. 2012. “Editorial photographs and patterns of practice.” Journalism Practice. Accessed: http://www.tandfonline.com/doi/abs/10.1080/17512786.2012.726836#.UbZN-L--1RQ Lemke, Jay. 1995. Textual Politics: Discourse and Social Dynamics. London: Taylor & Francis.

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.

The promise of justice reinvestment

Abstract: This article examines the notion and practice of Justice Reinvestment (‘JR’), an emerging approach addressing the high social and economic costs of soaring incarceration rates. JR invests in public safety by reallocating dollars from corrections budgets to finance education, housing, healthcare, and jobs in high-crime communities. Key distinguishing features of JR (including justice and asset mapping, budgetary devolution and localism, and the desirability of bipartisanship) are briefly outlined, followed by discussion of its recent emergence and application in the United States, and to a lesser extent in the United Kingdom. The prospects for the adoption of JR approaches in Australia are then considered, with particular reference to the high imprisonment rates of Indigenous people. If JR is to be promoted in the Australian context it is important that it be subject to critical scrutiny and therefore some of the key problems are briefly outlined, before a conclusion which emphasizes the potential benefits of JR.

A randomized controlled trial of a 10 percent CPP-ACP cream to reduce mutans streptococci colonization

Purpose The purpose of this study was to investigate the effectiveness of a 10 percent casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) cream to reduce mutans streptococci (MS) colonization and prevent early childhood caries. Methods The cohort was randomized at mean age of 11 days old to receive once-daily CPP-ACP cream (n=102) or no product (comparison group; n=89) from the time of first tooth eruption. All mothers were contacted by telephone at six, 12, and 18 months and advised to brush their children's teeth twice daily with low-dose fluoride toothpaste. At 24 months, all children were examined at a community clinic. Results At 24 months old, one out of 65 (2 percent) children in the CPP-ACP group had caries vs. four out of 58 (seven percent) in the comparison group (difference not statistically significant). There were fewer MS-positive children in the CPP-ACP group (26 percent) vs. the comparison group (47 percent; P=.02). A dose-response effect of CPP-ACP usage on MS was observed, where MS was present in eight percent of regular CPP-ACP users, 28 percent of irregular users, and 47 percent of non-users (P<.02). Conclusions CPP-ACP reduced the percentages of mutans streptococci-positive 24-month-old children, although it did not reduce caries prevalence.

The disenfranchisement of prisoners : Roach v Electoral Commissioner & Anor - modernity v feudalism

David Brown takes a road trip to Canberra for the Roach fixture at the High Court where modernity is attempting a fight-back against the resurrection of civil death. With echoes of Hunter S Thompson as rugby league follower, the author recounts a trip to Canberra to observe a case in which Vickie Lee Roach, an Indigenous woman prisoner, challenged (successfully as it later turns out) the Howard government's 2006 legislation disenfranchising all serving prisoners.