BRCA1 is an essential mediator of vinorelbine-induced apoptosis in mesothelioma

Therapeutic options for malignant pleural mesothelioma (MPM) are limited despite the increasing incidence globally. The vinca alkaloid vinorelbine exhibits clinical activity; however, to date, treatment optimization has not been achieved using biomarkers. BRCA1 regulates sensitivity to microtubule poisons; however, its role in regulating vinorelbine-induced apoptosis in mesothelioma is unknown. Here we demonstrate that BRCA1 plays an essential role in mediating vinorelbine-induced apoptosis, as evidenced by (1) the strong correlation between vinorelbine sensitivity and BRCA1 expression level; (2) induction of resistance to vinorelbine by BRCA1 using siRNA oligonucleotides; (3) dramatic down-regulation of BRCA1 following selection for vinorelbine resistance; and (4) the re-activation of vinorelbine-induced apoptosis following re-expression of BRCA1 in resistant cells. To determine whether loss of BRCA1 expression in mesothelioma was potentially relevant in vivo, BRCA1 immunohistochemistry was subsequently performed on 144 primary mesothelioma specimens. Loss of BRCA1 protein expression was identified in 38.9% of samples. Together, these data suggest that BRCA1 plays a critical role in mediating apoptosis by vinorelbine in mesothelioma, warranting its clinical evaluation as a predictive biomarker.

Climate change adaptation : a decision support framework to encourage environmentally responsible behaviour

Structured Abstract:
Purpose: Very few studies investigate environmentally responsible behaviour (ERB). This paper presents a new 'Awareness Behaviour Intervention Action' (ABIA) Decision Support Framework to sustain ERB.

Design/methodology/approach: Previous ERB programmes have failed to deliver lasting results; they have not appropriately understood and provided systems to address ERB (Costanzo et al., 1986). These programmes were based on assumptions (Moloney et al., 2010), which this paper addresses. The ABIA Framework has been developed through a case study of social housing tenants waiting for low or zero carbon homes.

Findings: The ABIA Framework enables a better understanding of current attitudes to environmental issues and provides support for ERB alongside technological interventions employed to promote and sustain carbon reduction.

Research limitations/implications: The ABIA Framework should be tested on individuals and communities in a variety of socio-economic, political and cultural contexts. This will help unpack how it can impact on the behaviours of individuals and communities including stakeholders.

Practical implications: This type of research and the ABIA Framework developed from it are crucial if the UK pledge to become the first country in the World where all new homes from 2016 are to be zero carbon.

Social implications: The Framework encourages both individual and community discussion and solving of sustainability issues.

Originality/value: There are few, if any, studies that have developed a framework which can be used to support behavioural change for adaptation to sustainable living in low or zero carbon homes.