Integrin α11β1 is expressed in breast cancer stroma and associates with aggressive tumor phenotypes

Cancer‐associated fibroblasts are essential modifiers of the tumor microenvironment. The collagen‐binding integrin α11β1 has been proposed to be upregulated in a pro‐tumorigenic subtype of cancer‐associated fibroblasts. Here, we analyzed the expression and clinical relevance of integrin α11β1 in a large breast cancer series using a novel antibody against the human integrin α11 chain. Several novel monoclonal antibodies against the integrin α11 subunit were tested for use on formalin‐fixed paraffin‐embedded tissues, and Ab 210F4B6A4 was eventually selected to investigate the immunohistochemical expression in 392 breast cancers using whole sections. mRNA data from METABRIC and co‐expression patterns of integrin α11 in relation to αSMA and cytokeratin‐14 were also investigated. Integrin α11 was expressed to varying degrees in spindle‐shaped cells in the stroma of 99% of invasive breast carcinomas. Integrin α11 co‐localized with αSMA in stromal cells, and with αSMA and cytokeratin‐14 in breast myoepithelium. High stromal integrin α11 expression (66% of cases) was associated with aggressive breast cancer features such as high histologic grade, increased tumor cell proliferation, ER negativity, HER2 positivity, and triple‐negative phenotype, but was not associated with breast cancer specific survival at protein or mRNA levels. In conclusion, high stromal integrin α11 expression was associated with aggressive breast cancer phenotypes.publishedVersio

Non-western immigrants' satisfaction with the general practitioners' services in Oslo, Norway

<p>Abstract</p> <p>Background</p> <p>Over the last few years the number of immigrants from the non-western parts of the world living in Oslo, has increased considerably. We need to know if these immigrants are satisfied with the health services they are offered. The aim of this study was to assess whether the immigrants' level of satisfaction with visits to general practitioners was comparable with that for ethnic Norwegians.</p> <p>Methods</p> <p>Two population-based surveys, the Oslo Health Study and the Oslo Immigrant Health Study, were performed on selected groups of Oslo citizens in 2000 and 2002. The response rates were 46% and 33%, respectively. In all, 11936 Norwegians and 1102 non-western immigrants from the Oslo Health Study, and 1774 people from the Oslo Immigrant Health Study, were included in this analysis. Non-western immigrants' and ethnic Norwegians' level of satisfaction with visits to general practitioners were analysed with respect to age, gender, health, working status, and use of translators. Bivariate (Chi square) and multivariate analyses (logistic regression) were performed.</p> <p>Results</p> <p>Most participants were either moderately or very satisfied with their last visit to a general practitioner. Non-western immigrants were less satisfied than Norwegians. Dissatisfaction among the immigrants was associated with young age, a feeling of not having good health, and coming from Turkey, Iran, Pakistan, or Vietnam as compared to Sri Lanka. The attendance rates in the surveys were rather low and lowest among the non-western immigrants.</p> <p>Conclusion</p> <p>Although the degree of satisfaction with the primary health care was relatively high among the participants in these surveys, the non-western immigrants in this study were less satisfied than ethnic Norwegians with their last visit to a general practitioner. The rather low response rates opens for the possibility that the degree of satisfaction may not be representative for all immigrants.</p

Barriers and motivators to gaining access to smoking cessation services amongst deprived smokers – a qualitative study

BACKGROUND: Smoking is strongly associated with disadvantage and is an important contributor to inequalities in health. Smoking cessation services have been implemented in the UK targeting disadvantaged smokers, but there is little evidence available on how to design services to attract this priority group. METHODS: We conducted focus groups with 39 smokers aged 21–75 from the most socio-economically deprived areas of Nottingham UK who had made an unsuccessful attempt to quit within the last year without using smoking cessation services, to identify specific barriers or motivators to gaining access to these services. RESULTS: Barriers to use of existing services related to fear of being judged, fear of failure, a perceived lack of knowledge about existing services, a perception that available interventions – particularly Nicotine Replacement Therapy – are expensive and ineffective, and negative media publicity about bupropion. Participants expressed a preference for a personalised, non-judgemental approach combining counselling with affordable, accessible and effective pharmacological therapies; convenient and flexible timing of service delivery, and the possibility of subsidised complementary therapies. CONCLUSION: We conclude that smokers from these deprived areas generally had low awareness of the services available to help them, and misconceptions about their availability and effectiveness. A more personalised approach to promoting services that are non-judgemental, and with free pharmacotherapy and flexible support may encourage more deprived smokers to quit smoking

Similar decline in mortality rate of older persons with and without type 2 diabetes between 1993 and 2004 the Icelandic population-based Reykjavik and AGES-Reykjavik cohort studies.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.A decline in mortality rates due to cardiovascular diseases and all-cause mortality has led to increased life expectancy in the Western world in recent decades. At the same time, the prevalence of type 2 diabetes, a disease associated with a twofold excess risk of cardiovascular disease and mortality, has been increasing. The objective of this study was to estimate the secular trend of cardiovascular and all-cause mortality rates in two population-based cohorts of older persons, with and without type 2 diabetes, examined 11 years apart.1506 participants (42% men) from the population-based Reykjavik Study, examined during 1991-1996 (median 1993), mean age 75.0 years, and 4814 participants (43% men) from the AGES-Reykjavik Study, examined during 2002-2006 (median 2004), mean age 77.2 years, age range in both cohorts 70-87 years. The main outcome measures were age-specific mortality rates due to cardiovascular disease and all causes, over two consecutive 5.7- and 5.3-year follow-up periods.A 32% decline in cardiovascular mortality rate and a 19% decline in all-cause mortality rate were observed between 1993 and 2004. The decline was greater in those with type 2 diabetes, as illustrated by the decline in the adjusted hazard ratio of cardiovascular mortality in individuals with diabetes compared to those without diabetes, from 1.88 (95% CI 1.24-2.85) in 1993 to 1.46 (95% CI 1.11-1.91) in 2004. We also observed a concurrent decrease in major cardiovascular risk factors in both those with and without diabetes. A higher proportion of persons with diabetes received glucose-lowering, hypertensive and lipid-lowering medication in 2004.A decline in cardiovascular and all-cause mortality rates was observed in older persons during the period 1993-2004, in both those with and without type 2 diabetes. This decline may be partly explained by improvements in cardiovascular risk factors and medical treatment over the period studied. However, type 2 diabetes still persists as an independent risk factor for cardiovascular mortality.National Institute of Health/N01-AG-1-2100 NIA Intramural Research Program Icelandic Heart Association (Hjartavernd) Icelandic Parliament (Althingi

Evaluation of the performance of elastomeric pumps in practice : are we under delivering on chemotherapy treatments?

Background and aims: Elastomeric pumps are widely used to facilitate ambulatory chemotherapy, and studies have shown that they are safe and well received by patients. Despite these advantages, their end of infusion time can fluctuate significantly. The aim of this research was to observe the performance of these pumps in real practice and to evaluate patients' satisfaction. Methods: This was a two-phase study conducted at three cancer units over 6 months. Phase-1 was an observational study recording the status of pumps at the scheduled disconnection time and noting remaining volume of infusion. Phase-2 was a survey of patients and their perception/satisfaction. Ethical approval was granted. Results: A total of 92 cases were observed covering 50 cases disconnected at hospital and 42 disconnected at home. The infusion in 40% of hospital disconnection cases was slow, with patients arriving at hospital with unfinished pumps; 58% of these had an estimated remaining volume which exceeded 10 mL with 35% exceeded 20 mL. In 73% of these cases, and regardless of the remaining volume, the patient was disconnected and the pump was discarded. Conclusions: The performance of pumps varied, which affected nurse workload and patients' waiting-times. A smart system is an option to monitor the performance of pumps and to predict their accuracy

The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation

<p>Abstract</p> <p>Background</p> <p>The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, methylation-dependent silencing of SOX11 has been reported for B cell lymphomas and indicates that epigenetic drugs may be used to re-express this tumour suppressor, but information on SOX11 promoter methylation in EOC is still lacking.</p> <p>Methods</p> <p>SOX11 expression and clinicopathological data was compared using χ²test in a cohort of 154 cases of primary invasive EOC. Kaplan-Meier analysis and the log rank test were applied to evaluate ovarian cancer-specific survival (OCSS) and overall survival (OS) in strata, according to SOX11 expression. Also, the methylation status of the SOX11 promoter was determined by sodium bisulfite sequencing and methylation specific PCR (MSP). Furthermore, the effect of ectopic overexpression of SOX11 on proliferation was studied through [3H]-thymidine incorporation.</p> <p>Results</p> <p>SOX11 expression was associated with an improved survival of patients with high grade EOC, although not independent of stage. Further analyses of EOC cell lines showed that SOX11 mRNA and protein were expressed in two of five cell lines, correlating with promoter methylation status. Demethylation was successfully performed using 5'-Aza-2'deoxycytidine (5-Aza-dC) resulting in SOX11 mRNA and protein expression in a previously negative EOC cell line. Furthermore, overexpression of SOX11 in EOC cell lines confirmed the growth regulatory role of SOX11.</p> <p>Conclusions</p> <p>SOX11 is a functionally associated protein in EOC with prognostic value for high-grade tumours. Re-expression of SOX11 in EOC indicates a potential use of epigenetic drugs to affect cellular growth in SOX11-negative tumours.</p