Loss of p38δ mitogen-activated protein kinase expression promotes oesophageal squamous cell carcinoma proliferation, migration and anchorage-independent growth.

Oesophageal cancer is an aggressive tumour which responds poorly to both chemotherapy and radiation therapy and has a poor prognosis. Thus, a greater understanding of the biology of oesophageal cancer is needed in order to identify novel therapeutic targets. Among these targets p38 MAPK isoforms are becoming increasingly important for a variety of cellular functions. The physiological functions of p38α and -β are now well documented in contrast to -γ and -δ which are comparatively under-studied and ill-defined. A major obstacle to deciphering the role(s) of the latter two p38 isoforms is the lack of specific chemical activators and inhibitors. In this study, we analysed p38 MAPK isoform expression in oesophageal cancer cell lines as well as human normal and tumour tissue. We observed specifically differential p38δ expression. The role(s) of p38δ and active (phosphorylated) p38δ (p-p38δ) in oesophageal squamous cell carcinoma (OESCC) was delineated using wild-type p38δ as well as active p-p38δ, generated by fusing p38δ to its upstream activator MKK6b(E) via a decapeptide (Gly-Glu)5 linker. OESCC cell lines which are p38δ-negative (KE-3 and -8) grew more quickly than cell lines (KE-6 and -10) which express endogenous p38δ. Re-introduction of p38δ resulted in a time-dependent decrease in OESCC cell proliferation which was exacerbated with p-p38δ. In addition, we observed that p38δ and p-p38δ negatively regulated OESCC cell migration in vitro. Finally both p38δ and p-p38δ altered OESCC anchorage-independent growth. Our results suggest that p38δ and p-p38δ have a role in the suppression of OESCC. Our research may provide a new potential target for the treatment of oesophageal cancer.

Diageo's 'Stop Out of Control Drinking' campaign in Ireland: an analysis

Background: It has been argued that the alcohol industry uses corporate social responsibility activities to influence policy and undermine public health, and that every opportunity should be taken to scrutinise such activities. This study analyses a controversial Diageo-funded ‘responsible drinking’ campaign (“Stop out of Control Drinking”, or SOOCD) in Ireland. The study aims to identify how the campaign and its advisory board members frame and define (i) alcohol-related harms, and their causes, and (ii) possible solutions. Methods: Documentary analysis of SOOCD campaign material. This includes newspaper articles (n = 9), media interviews (n = 11), Facebook posts (n = 92), and Tweets (n = 340) produced by the campaign and by board members. All material was coded inductively, and a thematic analysis undertaken, with codes aggregated into sub-themes. Results: The SOOCD campaign utilises vague or self-defined concepts of ‘out of control’ and ‘moderate’ drinking, tending to present alcohol problems as behavioural rather than health issues. These are also unquantified with respect to actual drinking levels. It emphasises alcohol-related antisocial behaviour among young people, particularly young women. In discussing solutions to alcohol-related problems, it focuses on public opinion rather than on scientific evidence, and on educational approaches and information provision, misrepresenting these as effective. “Moderate drinking” is presented as a behavioural issue (“negative drinking behaviours”), rather than as a health issue. Conclusions: The ‘Stop Out of Control Drinking’ campaign frames alcohol problems and solutions in ways unfavourable to public health, and closely reflects other Diageo Corporate Social Responsibility (CSR) activity, as well as alcohol and tobacco industry strategies more generally. This framing, and in particular the framing of alcohol harms as a behavioural issue, with the implication that consumption should be guided only by self-defined limits, may not have been recognised by all board members. It suggests a need for awareness-raising efforts among the public, third sector and policymakers about alcohol industry strategies