High sensitivity cytokine detection in acute coronary syndrome reveals up-regulation of interferon gamma and interleukin-10 post myocardial infarction.

Inflammation is an important element in the development and destabilization of atherosclerotic plaque. Using a high sensitivity multiplex assay, previously untested in the context of atherosclerotic disease, we determined serum concentrations of GM-CSF, IFNgamma, IL-1beta, IL-2, IL-10, IL-12p70, TNF alpha, IL-6, and IL-8 in 48 Myocardial Infarction (MI) patients, 14 Unstable Angina (UA) patients and 12 healthy controls. IFNgamma levels were significantly higher in MI compared to UA (p=0.

Expression of a protease-resistant insulin-like growth factor-binding protein-4 inhibits tumour growth in a murine model of breast cancer.

Background: Insulin-like growth factor 1 (IGF1) promotes breast cancer and disease progression. Bioavailability of IGF1 is modulated by IGF-binding proteins (IGFBPs). IGFBP4 inhibits IGF1 activity but cleavage by pregnancy-associated plasma protein-A (PAPP-A) protease releases active IGF1.

Selected highlights of the Third Annual Biomarkers Congress: from discovery to validation in the drug development arena.

This report summarises selected presentations that focused on aspects of biomarker discovery and validation, imaging in preclinical and clinical development and biomarkers in clinical drug development, as discussed during the Third Annual Biomarkers Congress held in Manchester, UK on 14 - 15 May 2008. More than 140 delegates attended this event to discuss the application of biomarkers to all facets of the drug development process. The conference consisted of five intensive streams discussing current and future directions in: i) biomarker discovery and validation; ii) molecular diagnostics, data integration, data analysis, modelling and bioinformatics; iii) biomarkers in clinical drug development; iv) biomarker discovery and validation: therapeutic areas; and v) imaging in preclinical and clinical development and safety biomarkers.

Proteomic analysis of factors released from p21-overexpressing tumour cells.

The p21Waf1/Cip1/Sdi1 cyclin-dependent kinase inhibitor is a key regulator of cell cycle progression and has also been observed to influence the expression of genes associated with several age-related disorders. Previous work has shown that expression of p21 in tumour cells mediates an antiapoptotic and mitogenic paracrine effect, which is in contrast to the arrested state of p21-expressing cells. Here, we have employed SELDI-MS technology to characterise, at a proteomic level, factors released from HT-1080 human fibrosarcoma cells displaying inducible p21 expression.

Fibulins and cancer: friend or foe?

The fibulins are a family of secreted glycoproteins, which are characterised by repeated epidermal-growth-factor-like domains and a unique C-terminal structure. Six distinct fibulin genes, encoding at least nine protein products generated by alternative splicing, have been identified. Considerable evidence is available pointing towards a structural role for fibulins within the extracellular matrix.