CA 15-3 is predictive of response and disease recurrence following treatment in locally advanced breast cancer

BACKGROUND: Primary chemotherapy (PC) is used for down-staging locally advanced breast cancer (LABC). CA 15-3 measures the protein product of the MUC1 gene and is the most widely used serum marker in breast cancer. METHODS: We retrospectively investigated the role of CA 15-3 in conjunction with other clinico-pathological variables as a predictor of response and time to disease recurrence following treatment in LABC. Pre and post primary chemotherapy serum concentrations of CA 15-3 together with other variables were reviewed and related to four outcomes following primary chemotherapy (clinical response, pathological response, time to recurrence and time to progression). Persistently elevated CA 15-3 after PC was considered as consecutively high levels above the cut off point during and after PC. RESULTS: 73 patients were included in this study. Patients received PC (AC or AC-T regimen) for locally advanced breast cancer. 54 patients underwent surgery. The median follow up was 790 days. Patients with high concentrations of CA 15-3 before PC treatment had a poor clinical (p = 0.013) and pathological (p = 0.044) response. Together with Her-2/neu expression (p = 0.009) and tumour lympho-vascular space invasion (LVI) (p = 0.001), a persistently elevated CA 15-3 post PC (p = 0.007) was an independent predictive factor of recurrence following treatment in LABC. CONCLUSION: Elevated CA 15-3 level is predictive of a poor response to chemotherapy. In addition, persistently elevated CA 15-3 levels post chemotherapy in conjunction with lympho-vascular invasion and HER2 status predict a reduced disease free survival following treatment in locally advanced breast cancer

A quantitative risk assessment of E.coli 0157:H7 in Irish minced beef

End of Project ReportA national quantitative risk assessment was undertaken for minced beef in the Republic of Ireland. The objective was to estimate the probability of E. coli O157:H7 infection from consumption of Irish beef and to investigate the parts of the beef chain contributing most to the risk posed by this pathogen.The quantitative risk assessment was broken into 3 main modules: 1) production of boxed beef trimmings; 2) processing of trimmings and burger formation and 3) retail/domestic consumption phase. Key points in each module (beef hide, beef trimmings and beef products at retail) were validated using data derived from microbiology sampling at beef abattoirs, supermarkets and butchers’ shops in Ireland

Farm to Fork Quantitative Risk Assessment of Listeria monocytogenes Contamination in Raw and Pasteurized Milk Cheese in Ireland

International audienc

The Iron-Regulated iupABC Operon Is Required for Saprophytic Growth of the Intracellular Pathogen Rhodococcus equi at Low Iron Concentrations

Rhodococcus equi is a facultative intracellular pathogen which proliferates rapidly in both manure-enriched soil and alveolar macrophages. Although both environments are characterized by extremely low concentrations of free iron, very little is known regarding the strategies employed by R. equi to thrive under these conditions. This paper reports the characterization of an R. equi transposome mutant that fails to grow at low iron concentrations. The transposome was shown to be inserted into iupA, the first gene of the iupABC operon encoding an ABC transport system highly similar to siderophore uptake systems. Disruption of the iupA gene also resulted in a failure of R. equi to utilize heme and hemoglobin as a source of iron. Introduction of the iupABC operon in trans restored the wild-type phenotype of the mutant strain. iupABC transcripts were 180-fold more abundant in R. equi grown in iron-depleted medium than in organisms grown in iron-replete medium. Proliferation of the iupABC mutant strain in macrophages was comparable to that of the wild-type strain. Furthermore, the iupABC mutant was not attenuated in mice, showing that the iupABC operon is not required for virulence

ADAM8 expression in invasive breast cancer promotes tumor dissemination and metastasis

International audienceThe transmembrane metalloprotease-disintegrin ADAM8 mediates cell adhesion and shedding of ligands, receptors and extracellular matrix components. Here, we report that ADAM8 is abundantly expressed in breast tumors and derived metastases compared to normal tissue, especially in triple-negative breast cancers (TNBCs). Furthermore, high ADAM8 levels predicted poor patient outcome. Consistently, ADAM8 promoted an aggressive phenotype of TNBC cells in culture. In a mouse orthotopic model, tumors derived from TNBC cells with ADAM8 knockdown failed to grow beyond a palpable size and displayed poor vascularization. Circulating tumor cells and brain metastases were also significantly reduced. Mechanisti-cally, ADAM8 stimulated both angiogenesis through release of VEGF-A and transendothelial cell migration via β1-integrin activation. In vivo, treatment with an anti-ADAM8 antibody from the time of cell inoculation reduced primary tumor burden and metastases. Furthermore, antibody treatment of established tumors profoundly decreased metastases in a resection model. As a non-essential protein under physiological conditions, ADAM8 represents a promising novel target for treatment of TNBCs, which currently lack targeted therapies and frequently progress with fatal dissemination

Mortgage-related issues in a crisis economy: evidence from rural households in Ireland

The recent economic crisis has demonstrated the extent to which households are exposed to the financialisation of advanced economies. Much of the debate surrounding the reasons for the crisis has centred on the role of neoliberal policies and particularly lax mortgage lending practices among financial institutions. This paper explores how neoliberal ideas were applied to property and development during the Irish house-building boom. Drawing on questionnaire survey data across five case study locations, it examines the mortgage practices of rural households during the boom period and their existing conditions in the current burst. In addition, the impacts and consequences of the neoliberalisation of the rural mortgage market for rural households within the context of the failure of these policies, a major housing crash and a neoliberal policy fix based on severe austerity measures is examined. Our results point towards the extreme hardship and stress being felt by rural households and highlight, through the lens of rural housing, the extent to which the practices and consequences of neoliberal policy in the mortgage arena are varied spatially in rural areas.Author has checked copyright13/05/13 R