Occupational and non-occupational risk factors in bladder cancer patients in an industrialized area located in former East-Germany [Berufliche und außerberufliche Risikofaktoren für das Harnblasenkarzinom in einem ehemaligen Industriegebiet der neuen Bundesländer]

Purpose: Several occupational carcinogens are metabolized by polymorphic enzymes. The distribution of the polymorphic enzymes N-acetyltransferase 2 (NAT2; substrates: aromatic amines), glutathione S-transferase M1 (GSTM1; substrates: e.g., reactive metabolites of polycyclic aromatic hydrocarbons), and glutathione S-transferase T1 (GSTT1; substrates: small molecules with 1-2 carbon atoms) were investigated. Material and Methods: At the urological department in Lutherstadt Wittenberg, 136 patients with a histologically proven transitional cell cancer of the urinary bladder were investigated for all occupations performed for more than 6 months. Several occupational and non-occupational risk factors were asked. The genotypes of NAT2, GSTM1, and GSTT1 were determined from leucocyte DNA by PCR. Results: Compared to the general population in Middle Europe, the percentage of GSTT1 negative persons (22.1 %) was ordinary; the percentage of slow acetylators (59.6%) was in the upper normal range, while the percentage of GSTM1 negative persons (58.8%) was elevated in the entire group. Shifts in the distribution of the genotypes were observed in subgroups who had been exposed to asbestos (6/6 GSTM1 negative, 5/6 slow acetylators), rubber manufacturing (8/10 GSTM1 negative), and chlorinated solvents (9/15 GSTM1 negative). Conclusions: The overrepresentation of GSTM1 negative bladder cancer patients also in this industrialized area and more pronounced in several occupationally exposed subgroups points to an impact of the GSTM1 negative genotype in bladder carcinogenesis. [Article in German]

Tetraspanins as regulators of the tumour microenvironment : implications for metastasis and therapeutic strategies

One of the hallmarks of cancer is the ability to activate invasion and metastasis (Hanahan et al., 2011). Cancer morbidity and mortality are largely related to the spread of the primary, localised tumour to adjacent and distant sites (Pantel et al., 2004). Appropriate management and treatment decisions of predicting metastatic disease at the time of diagnosis is thus crucial, which supports better understanding of the metastatic process. There are common events that occur during metastasis: dissociation from the primary tumour mass, reorganisation/remodelling of extracellular matrix, cell migration, recognition and transversal of endothelial cells and the vascular circulation and lodgement and proliferation within ectopic stroma (Wells, 2006). One of the key and initial events is the increased capability of cancer cells to move, escaping the regulation of normal physiological control. The cellular cytoskeleton plays an important role in cancer cell motility and active cytoskeletal rearrangement can result in metastatic disease. This active change in cytoskeletal dynamics results in manipulation of plasma membrane and cellular balance between cellular adhesion and motility which in turn determines cancer cell movement. Members of the tetraspanins play important roles in regulation of cancer migration and cancer-endothelial cell interactions, which are critical for cancer invasion and metastasis. Their involvements in active cytoskeletal dynamics, cancer metastasis and potential clinical application will be discussed in this review. In particular, tetraspanin member, CD151, is highlighted for its major role in cancer invasion and metastasis

Keeping our nursing and midwifery workforce : factors that support non-practising clinicians to return to practice

BACKGROUND: Within Australia and internationally (Health Workforce Australia, 2012) an increasing and on-going nursing workforce shortage is documented. Recent international estimates indicate that there will be ongoing and significant gaps in the supply of a nursing workforce; the United Kingdom is predicted to have a reduction of 12.12% nurses over the coming eight years if a current 'steady state' is maintained (Buchan and Seacombe, 2011); Canada is predicted to have a shortage of 60,000 nurses by 2022 (Tomblin et al., 2012) with Australia's anticipated nursing shortage reported as over 90,000 by the year 2025 (Health Workforce Australia, 2012). Queensland Health in response to their tracked emerging nursing and midwifery workforce shortages developed a nursing and midwifery refresher programme to return registered staff back to the workforce. A study was undertaken between 2008 and 2010 to provide an understanding of how non-practising nurses and midwives maybe supported back into the workforce. METHODS: Programme applicants (444) were invited to respond to an on-line survey designed to understand what aspects of the programme supported their learning and ability to return to the workforce. This number represents those who applied but not all completed or commenced the programme. Descriptive statistics (Polit and Beck, 2008) were used to collate quantifiable survey responses and free text and unsolicited responses were themed. RESULTS: The survey received a 35.5% response rate (n=158) with a return of 20% of unsolicited comments in the form of e-mail responses which were included in the themed results. Key themes supporting participants' learning and ability to return to the workforce were: Respondents were 94% female and 6% male, with 37.7% >51 years of age. Child rearing was the foremost reason for female staff relinquishing workforce roles (36.6%). The primary reason for returning to the workforce was maintenance of registration (40.5%). Both theory and clinical placement components were seen by participants as contributing to their confidence to return to the health workforce. CONCLUSION: The Queensland Nursing and Midwifery Refresher Programs provided a structured programme for registered, non-practising nurses and midwives to return to the Queensland Health workforce. Responses indicated that clinical supervision and contract learning should be central to a return to workforce induction programme for registered but non-practising nurses and midwives. The majority of nurses and midwives returning to the workforce were approaching retirement age in 10-15 years.

Incidence of paediatric fatal and non-fatal low speed vehicle run over events in Queensland, Australia : eleven year analysis

Background The purpose of this study was to estimate the incidence of fatal and non-fatal Low Speed Vehicle Run Over (LSVRO) events among children aged 0–15 years in Queensland, Australia, at a population level. Methods Fatal and non-fatal LSVRO events that occurred in children resident in Queensland over eleven calendar years (1999-2009) were identified using ICD codes, text description, word searches and medical notes clarification, obtained from five health related data bases across the continuum of care (pre-hospital to fatality). Data were manually linked. Population data provided by the Australian Bureau of Statistics were used to calculate crude incidence rates for fatal and non-fatal LSVRO events. Results There were 1611 LSVROs between 1999–2009 (IR = 16.87/100,000/annum). Incidence of non-fatal events (IR = 16.60/100,000/annum) was 61.5 times higher than fatal events (IR = 0.27/100,000/annum). LSVRO events were more common in boys (IR = 20.97/100,000/annum) than girls (IR = 12.55/100,000/annum), and among younger children aged 0–4 years (IR = 21.45/100000/annum; 39% or all events) than older children (5–9 years: IR = 16.47/100,000/annum; 10–15 years IR = 13.59/100,000/annum). A total of 896 (56.8%) children were admitted to hospital for 24 hours of more following an LSVRO event (IR = 9.38/100,000/annum). Total LSVROs increased from 1999 (IR = 14.79/100,000) to 2009 (IR = 18.56/100,000), but not significantly. Over the 11 year period, there was a slight (non –significant) increase in fatalities (IR = 0.37-0.42/100,000/annum); a significant decrease in admissions (IR = 12.39–5.36/100,000/annum), and significant increase in non-admissions (IR = 2.02-12.77/100,000/annum). Trends over time differed by age, gender and severity. Conclusion This is the most comprehensive, population-based epidemiological study on fatal and non-fatal LSVRO events to date. Results from this study indicate that LSVROs incur a substantial burden. Further research is required on the characteristics and risk factors associated with these events, in order to adequately inform injury prevention. Strategies are urgently required in order to prevent these events, especially among young children aged 0-4 years.

Enhancing MRI of prostate cancer using PSMA-targeting iron oxide magnetic nanoparticles

Introduction Novel imaging techniques for prostate cancer (PCa) are required to improve staging and real-time assessment of therapeutic response. We performed preclinical evaluation of newly-developed, biocompatible magnetic nanoparticles (MNPs) conjugated with J591, an antibody specific for prostate specific membrane antigen (PSMA), to enhance magnetic resonance imaging (MRI) of PCa. PSMA is expressed on ∼90% of PCa, including those that are castrate-resistant, rendering it as a rational target for PCa imaging. Materials and Methods The specificity of J591 for PSMA was confirmed by flow cytometric analysis of several PCa cell lines of known PSMA status. MNPs were prepared, engineered to the appropriate size, labeled with DiR fluorophore, and their toxicity to a panel of PC cells was assessed by in vitro Alamar Blue assay. Immunohistochemistry, fluorescence microscopy and Prussian Blue staining (iron uptake) were used to evaluate PSMA specificity of J591-MNP conjugates. In vivo MRI studies (16.4T MRI system) were performed using live immunodeficient mice bearing orthotopic LNCaP xenografts and injected intravenously with J591-MNPs or MNPs alone. Results MNPs were non-toxic to PCa cells. J591-MNP conjugates showed no compromise in specificity of binding to PSMA+ cells and showed enhanced iron uptake compared with MNPs alone. In vivo, tumour targeting (significant MR image contrast) was evident in mice injected with J591-MNPs, but not MNPs alone. Resected tumours from targeted mice had an accumulation of MNPs, not seen in normal control prostate. Conclusions Application of PSMA-targeting MNPs into conventional MRI has potential to enhance PCa detection and localization in real-time, improving patient management.

A biomarker panel to discriminate between systemic inflammatory response syndrome and sepsis and sepsis severity

Introduction: In this study, we report on initial efforts to discover putative biomarkers for differential diagnosis of a systemic inflammatory response syndrome (SIRS) versus sepsis; and different stages of sepsis. In addition, we also investigated whether there are proteins that can discriminate between patients who survived sepsis from those who did not. Materials and Methods: Our study group consisted of 16 patients, of which 6 died and 10 survived. We daily measured 28 plasma proteins, for the whole stay of the patients in the ICU. Results: We observed that metalloproteinases and sE-selectin play a role in the distinction between SIRS and sepsis, and that IL-1, IP-10, sTNF-R2 and sFas appear to be indicative for the progression from sepsis to septic shock. A combined measurement of MMP-3, -10, IL-1, IP-10, sIL-2R, sFas, sTNF-R1, sRAGE, GM-CSF, IL-1 and Eotaxin allows for a good separation of patients that survived from those that died (mortality prediction with a sensitivity of 79% and specificity of 86%). Correlation analysis suggests a novel interaction between IL-1a and IP-10. Conclusion: The marker panel is ready to be verified in a validation study with or without therapeutic intervention.

Running shoes increase Achilles tendon load in walking : an acoustic propagation study

Background: Footwear remains a prime candidate for the prevention and rehabilitation of Achilles tendinopathy as it is thought to decrease tension in the tendon through elevation of the heel. However, evidence for this effect is equivocal. Purpose: This study used an acoustic transmission technique to investigate the effect of running shoes on Achilles tendon loading during barefoot and shod walking. Methods: Acoustic velocity was measured in the Achilles tendon of twelve recreationally–active males (age, 31±9 years; height, 1.78±0.06 m; weight, 81.0±16.9 kg) during barefoot and shod walking at matched self–selected speed (3.4±0.7 km/h). Standard running shoes incorporating a 10– mm heel offset were used. Vertical ground reaction force and spatiotemporal parameters were determined with an instrumented treadmill. Axial acoustic velocity in the Achilles tendon was measured using a custom built ultrasonic device. All data were acquired at a rate of 100 Hz during 10s of steady–state walking. Statistical comparisons between barefoot and shod conditions were made using paired t–tests and repeated measure ANOVAs. Results: Acoustic velocity in the Achilles tendon was highly reproducible and was typified by two maxima (P1, P2) and minima (M1, M2) during walking. Footwear resulted in a significant increase in step length, stance duration and peak vertical ground reaction force compared to barefoot walking. Peak acoustic velocity in the Achilles tendon (P1, P2) was significantly higher with running shoes. Conclusions: Peak acoustic velocity in the Achilles tendon was higher with footwear, suggesting that standard running shoes with a 10–mm heel offset increase tensile load in the Achilles tendon. Although further research is required, these findings question the therapeutic role of standard running shoes in Achilles tendinopathy.

2nd ESMO consensus conference on lung cancer : early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, earlystage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on early-stage disease. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

2nd ESMO Consensus Conference on Lung Cancer : non-small-cell lung cancer first-line/second and further lines in advanced disease

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, early stage disease and locally-advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on 1st line / 2nd and further lines of treatment in advanced disease. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Functions and therapeutic roles of exosomes in cancer

The role of exosomes in cancer development has become the focus of much research, due to the many emerging roles possessed by exosomes. These micro-vesicles that are ubiquitously released in to the extracellular milieu, have been found to regulate immune system function, particularly in tumorigenesis, as well as conditioning future metastatic sites for the attachment and growth of tumor tissue. Through an interaction with a range of host tissue, exosomes are able to generate a pro-tumor environment that is essential for carcinogenesis. Herein, we discuss the contents of exosomes and their contribution to tumorigenesis, as well as their role in chemotherapeutic resistance and the development of novel cancer treatments and the identification of cancer biomarkers.

Relationship between EGFR expression, EGFR mutation status, and the efficacy of chemotherapy plus cetuximab in FLEX study patients with advanced non-small-cell lung cancer

INTRODUCTION: The phase III FLEX study (NCT00148798) in advanced non-small-cell lung cancer indicated that the survival benefit associated with the addition of cetuximab to cisplatin and vinorelbine was limited to patients whose tumors expressed high levels of epidermal growth factor receptor (EGFR) (immunohistochemistry score of >/=200; scale 0-300). We assessed whether the treatment effect was also modulated in FLEX study patients by tumor EGFR mutation status. METHODS: A tumor mutation screen of EGFR exons 18 to 21 included 971 of 1125 (86%) FLEX study patients. Treatment outcome in low and high EGFR expression groups was analyzed across efficacy endpoints according to tumor EGFR mutation status. RESULTS: Mutations in EGFR exons 18 to 21 were detected in 133 of 971 tumors (14%), 970 of which were also evaluable for EGFR expression level. The most common mutations were exon 19 deletions and L858R (124 of 133 patients; 93%). In the high EGFR expression group (immunohistochemistry score of >/=200), a survival benefit for the addition of cetuximab to chemotherapy was demonstrated in patients with EGFR wild-type (including T790M mutant) tumors. Although patient numbers were small, those in the high EGFR expression group whose tumors carried EGFR mutations may also have derived a survival benefit from the addition of cetuximab to chemotherapy. Response data suggested a cetuximab benefit in the high EGFR expression group regardless of EGFR mutation status. CONCLUSIONS: The survival benefit associated with the addition of cetuximab to first-line chemotherapy for advanced non-small-cell lung cancer expressing high levels of EGFR is not limited by EGFR mutation status.

Second ESMO consensus conference on lung cancer : pathology and molecular biomarkers for non-small-cell lung cancer

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The Second ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on management of patients with nonsmall- cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, early stage disease, locally advanced disease and advanced (metastatic) disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on recommendations for pathology and molecular biomarkers in relation to the diagnosis of lung cancer, primarily non-small-cell carcinomas.

Tailored silica coated Ag nanoparticles for non-invasive surface enhanced Raman spectroscopy of biomolecular targets

Silica coated Ag nanoparticles with defined surface plasmon resonances are used to selectively detect and analyze protein cofactors in solution and on interfaces via surface enhanced resonance Raman spectroscopy. The silica coating has a surprisingly small effect on optical amplification but minimizes unwanted interactions between the protein and the nanoparticle.