The Joy and Roy of Irish

A short play as part of theatre company Kabosh's walking-tour-with-performances 'The West Awakes', focusing on aspects of the history and culture of West Belfast. My piece dramatised the contribution of Belfast Protestants and Unionists to the Irish language.

Cox-2 Promotes Chromogranin A Expression and Bioactivity: Evidence for a PGE2-Dependent Mechanism and the Involvement of a Proximal cAMP-Responsive Element.

Abstract The prostanoid biosynthetic enzyme cyclooxygenase-2 (Cox-2) is upregulated in several neuroendocrine tumors. The aim of the current study was to employ a neuroendocrine cell (PC12) model of Cox-2 over-expression to identify gene products that might be implicated in the oncogenic and/or inflammatory actions of this enzyme in the setting of neuroendocrine neoplasia. Expression array and real-time PCR analysis demonstrated that levels of the neuroendocrine marker chromogranin A (CGA) were 2-fold and 3.2-fold higher, respectively, in Cox-2 over-expressing cells (PCXII) vs their control (PCMT) counterparts. Immunocytochemical and immunoblotting analyses confirmed that both intracellular and secreted levels of CGA were elevated in response to Cox-2 induction. Moreover, exogenous addition of prostaglandin E2 (1u�­M), mimicked this effect in PCMT cells, while treatment of PCXII cells with the Cox-2 selective inhibitor NS-398 (100 nM) reduced CGA expression levels, thereby confirming the biospecificity of this finding. Levels of neurone specific enolase (NSE) were similar in the two cell lines, suggesting that the effect of Cox-2 on CGA expression was specific and not due to a global enhancement of neuroendocrine marker expression/differentiation. Cox-2-dependent CGA upregulation was associated with significantly increased chromaffin granule number and intracellular and secreted levels of dopamine. CGA promoter-driven reporter gene expression studies provided evidence that prostaglandin E2-dependent upregulation required a proximal cAMP-responsive element (CRE; -71 - -64 bp). This study is the first to demonstrate that Cox-2 upregulates both CGA expression and bioactivity in a neuroendocrine cell line and has major implications for the role of this polypeptide in the pathogenesis of neuroendocrine cancers in which Cox-2 is upregulated.

An evaluation of cyclooxygenase-2 as a prognostic biomarker in mid-gut carcinoid tumours

Background/Aims:Mid-gut carcinoids (MGC) are the most common of the gastrointestinal carcinoid tumours. There is a lack of reliable prognostic indicators for MGC. Cox-2 and Bcl-2 were evaluated as prognostic biomarkers in a cohort of well-characterised non-appendiceal MGC. Methods: Tissue from the primary MGC tumours of 37 patients was subjected to immunohistochemical detection of Cox-2 and Bcl-2. In 9 cases tissue from secondary lesions was also examined. The study assessed whether tumour-associated Cox-2 and Bcl-2 expression were related to patient survival. Results: Cox-2 expression was demonstrated in 30/36 primary tumours. When all tumours were analysed Cox-regression analysis indicated a trend towards worsening survival with increasing Cox-2 histoscore (intensity x proportion; hazard ratio 1.53, 95%CI 0.93, 2.52; p=0.09). Analysis of Cox-2 positive tumours revealed a highly significant association between increasing histoscore and decreased survival (hazard ratio 3.03, 95%CI 1.33, 6.91, p=0.008). Tumour-associated Bcl-2 expression had no effect on patient survival (hazard ratio 1.12, 95% CI 0.42, 2.99 p=0.82). There was no significant association between Cox-2 and Bcl-2 expression (ï?£2 p=0.16), or Cox-2 histoscore and Bcl-2 expression (MWU p=0.59). Analysis of the Cox-2 histoscores of primary tumours and their corresponding secondary lesions, revealed a statistically significant trend towards increasing histoscore in the latter (Wilcoxon p=0.04). Conclusions: This study has provided evidence that Cox-2 expression in primary MGC may be associated with a more negative prognostic outlook.