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Ho-Yen C.M.,Barts Cancer Institute | Green A.R.,Breast Unit | Rakha E.A.,Breast Unit | Brentnall A.R.,Wolfson Institute of Preventative Medicine | And 3 more authors.
Cancer | Year: 2014

BACKGROUND Basal-like (BL) breast cancer is an aggressive form of breast cancer with limited treatment options. Recent work has identified BL breast cancer as a biologically distinct form of triple-negative breast cancer, with a worse outlook. The receptor tyrosine kinase c-Met is a novel therapeutic target associated with reduced survival in breast cancer. Few studies have specifically addressed the association between c-Met and molecular subtype of breast cancer, yet this is a key consideration when selecting patients for clinical trials. The aim of this study is to evaluate c-Met expression in a large cohort of invasive breast cancers and in particular, its correlation with molecular subtype. METHODS Immunohistochemistry for c-Met was performed and evaluated on 1274 invasive breast cancers using tissue microarray technology. The c-Met scores were correlated with molecular subtype, survival, and other standard clinicopathological prognostic factors. RESULTS Multivariate logistic regression showed c-Met was independently associated with BL status (odds ratio = 6.44, 95% confidence interval = 1.74-23.78, P =.005). There was a positive correlation between c-Met and Her2 (P =.005) and an inverse correlation with tumor size (P <.001). C-Met was an independent poor prognostic factor at Cox regression analysis in all subtypes (hazard ratio = 1.85, 95% confidence interval = 1.07-3.19, P =.027) and there was a trend toward reduced survival in BL tumors overexpressing c-Met, but this was not significant. CONCLUSIONS C-Met is independently associated with BL breast cancer. In the future, patients with BL tumors should be included in clinical trials of anti-c-Met therapy. © 2013 American Cancer Society.

Cates M.J.,Torbay Hospital | Cates M.J.,University of Bristol | Dickinson C.J.,Wolfson Institute of Preventative Medicine | Hart E.C.J.,University of Bristol | Paton J.F.R.,University of Bristol
Current Hypertension Reports | Year: 2012

There is evidence of sympathetic overdrive in a significant proportion of patients with essential hypertension and an animal model of the condition, the spontaneously hypertensive rat (SHR). The reasons for this remain elusive. However, there is also evidence of narrowing of the arteries supplying the brainstem in the SHR and hypertensive humans. In this review, we discuss the possible role of brainstem hypoperfusion in driving increased sympathetic activity and hypertension. © Springer Science+Business Media, LLC 2012.

Baldwin D.R.,University of Nottingham | Duffy S.W.,Wolfson Institute of Preventative Medicine | Wald N.J.,Wolfson Institute of Preventive Medicine | Page R.,Liverpool Heart and Chest Hospital | And 2 more authors.
Thorax | Year: 2011

The UK Lung Screen (UKLS) is a randomised controlled trial of the use of low-dose multidetector CT for lung cancer screening. It completed the Health Technology Appraisal (HTA)-funded feasibility stage in October 2009 and the pilot UKLS will be initiated in early 2011. The pilot will randomise 4000 subjects to either low-dose CT screening or no screening. The full study, due to start in September 2012, if progression criteria are met, will randomise a further 28 000 subjects from seven centres in the UK. Subjects will be selected if they have sufficient risk of developing lung cancer according to the Liverpool Lung Project risk model. The UKLS employs the 'Wald Single Screen Design', which was modelled in the UKLS feasibility study. This paper describes the modelling of nodule management in UKLS by using volumetric analysis with a single initial screen design and follow-up period of 10 years. This modelling has resulted in the development and adoption of the UKLS care pathway, which will be implemented in the planned CT screening trial in the UK.

Blamey R.W.,Nottingham City Hospital | Bates T.,William Harvey Hospital | Chetty U.,Western General Hospital | Duffy S.W.,Wolfson Institute of Preventative Medicine | And 9 more authors.
European Journal of Cancer | Year: 2013

Background: The incidence of local recurrence (LR) after conservative surgery for early breast cancer without adjuvant therapy is unacceptably high even with favourable tumours. The aim of this study was to examine the effect of adjuvant therapies in tumours with excellent prognostic features. Methods: Patients with primary invasive breast cancer <2 cm diameter, grade 1 or good prognosis special type, and node negative, treated by wide local excision (WLE) with clear margins were randomised into a 2 × 2 clinical trial of factorial design with or without radiotherapy and with or without tamoxifen. Trial entry was allowed to either comparison or both. Findings: The actuarial breast cancer specific survival in 1135 randomised patients at 10 years was 96%. Analysis by intention to treat showed that LR after WLE was reduced in patients randomised to radiotherapy (RT) (HR 0.37, CI 0.22-0.61 p < 0.001) and to tamoxifen (HR 0.33, CI 0.15-0.70 p < 0.004). Actuarial analysis of patients entered into the four-way randomisation showed that LR after WLE alone was 1.9% per annum (PA) versus 0.7% with RT alone and 0.8% with tamoxifen alone. No patient randomised to both adjuvant treatments developed LR. Analysis by treatment received showed LR at 2.2% PA for surgery alone versus 0.8% for either adjuvant radiotherapy or tamoxifen and 0.2% for both treatments. Conclusions: Even in these patients with tumours of excellent prognosis, LR after conservative surgery without adjuvant therapy was still very high. This was reduced to a similar extent by either radiotherapy or tamoxifen but to a greater extent by the receipt of both treatments. © 2013 Elsevier Ltd. All rights reserved.

Johnson C.,University of Oxford | Mohan S.,University of Sydney | Praveen D.,All India Institute of Medical Sciences | Woodward M.,Wolfson Institute of Preventative Medicine | And 13 more authors.
BMJ Open | Year: 2014

Introduction: The scientific evidence base in support of salt reduction is strong but the data required to translate these insights into reduced population salt intake are mostly absent. The aim of this research project is to develop the evidence base required to formulate and implement a national salt reduction programme for India.Methods and analysis: The research will comprise three components: a stakeholder analysis involving government, industry, consumers and civil society organisations; a population survey using an agestratified and sex-stratified random samples drawn from urban (slum and non-slum) and rural areas of North and South India; and a systematic quantitative evaluation of the nutritional components of processed and restaurant foods. The stakeholder interviews will be analysed using qualitative methods to summarise the main themes and define the broad range of factors influencing the food environment in India. The population survey will estimate the mean daily salt consumption through the collection of 24 h urine samples with concurrent dietary surveys identifying the main sources of dietary sodium/salt. The survey of foods will record the nutritional composition of the chief elements of food supply. The findings from this research will be synthesised and proposals for a national salt reduction strategy for India will be developed in collaboration with key stakeholders.Ethics and dissemination: This study has been approved by the Human Research Ethics Committees of the University of Sydney and the Centre for Chronic Disease Control in New Delhi, and also by the Indian Health Ministry's Screening Committee. The project began fieldwork in February 2014 and will report the main results in 2016. The findings will be targeted primarily at public health policymakers and advocates, but will be disseminated widely through other mechanisms including conference presentations and peer-reviewed publications, as well as to the participating communities.

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