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Introduction: Lung carcinoids comprise a heterogeneous group of neuroendocrine tumors. Only few parameters have been identified that correlated with poor disease outcome, including 11q22-q25 deletions. New biomarkers are required to further improve diagnosis and prediction of prognosis. Aim(s): To identify differentially expressed genes between carcinoids with a favorable and poor outcome using high resolution gene-expression profiling, and to test their value as prognostic markers. Materials and methods: mRNA of five tumors with a favorable (>5yr survival) and five with a poor (distant metastasis / deceased) disease outcome was labeled and hybridized to 4x44k Agilent arrays, with a human pool expressing 70-80% of genes as a control. Results were validated by qRT-PCR and immunohistochemistry on an independent series of lung carcinoids. Results: Expression profiling revealed amongst others overexpression of the RET oncogene and repression of the homeobox gene OTP and CD44 in the poor prognosis group. In 54 frozen cases, low CD44 (p<0.0001) and OTP (p=0.0013), and high RET (p=0.0035) expression were significantly associated with decreased 15-year survival, outperforming WHO classification. Downregulation of CD44 and OTP expression was confirmed in tumors with a poor prognosis by immunohistochemistry. Conclusion: High resolution expression profiling unmasked new lung carcinoid candidate genes, of which CD44, OTP, and RET efficiently predict poor outcome. [ABSTRACT FROM AUTHOR]

Polyethylene wear and associated osteolysis can limit the longevity of total hip replacement. In recent years, many improvements have been made in the consolidation, manufacture, and sterilization of polyethylene acetabular components. These improvements provided reduced polyethylene wear and prolonged usefulness of total hip replacement. Recent advances in extensively cross-linking polyethylene offer the possibility to substantially further reduce wear in total hip replacement. Hip simulator wear testing demonstrates an order of magnitude reduction in wear resulting from cross-linking GUR 1050 polyethylene by exposure to 100 kGy of electron beam radiation followed by annealing to encourage cross-linking and to reduce residual free radicals. Clinical investigation will be required to validate the wear advantage of these materials in vivo. (Hip International 2002; 2: 103-7).

Background: Numerous detrimental side effects and/or lack of water-solubility of anticancer drugs often prove dose-limiting in chemotherapy. Water-soluble polymeric drug carriers may overcome/minimise many of these limitations., Materials and Methods: Aspartic acid polymers to which ferrocene-containing antineoplastic agents are covalently bound, were tested for cytotoxicity against murine EMT-6 cancer cells. Cell survival was measured by means of the colorometric 3-(4,5-dimethylthiazol-2-yl)-diphenyltertrazolium bromide assay., Results: The 90% lethal dosage of pure 3-ferrocenylbutanoic acid is 452 microg/mL LD90 for the polymeric derivative, expressed in terms of 3-ferrocenylbutanoic acid content, is only 65 microg/ml. A polymer structural effect in drug activity was evident: longer side chains linking drugs to polymer backbones enhanced drug activity. Drug activity is also enhanced if drug modifications (to enable drug anchoring) resulted in a lower ferrocenyl reduction potential., Conclusions: The effectivity of antineoplastic drugs may be enhanced by covalently anchoring them on suitable biodegradable water-soluble polymeric drug carriers.