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Biomedical subjects

G Devitt

Publications and source records attributed to G Devitt.

3 recordsLinked to original sources

Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization.

Renal cell carcinoma (RCC) are frequently chemo- and radiation resistant. Thus, there is a need for identifying biological features of these cells that could serve as alternative therapeutic targets. We performed suppression subtractive hybridization (SSH) on patient-matched normal renal and RCC tissue to identify variably regulated genes. 11 genes were strongly up-regulated or selectively expressed in more than one RCC tissue or cell line. Screening of filters containing cancer-related cDNAs confirmed overexpression of 3 of these genes and 3 additional genes were identified. These 14 differentially expressed genes, only 6 of which have previously been associated with RCC, are related to tumour growth/survival (EGFR, cyclin D1, insulin-like growth factor-binding protein-1 and a MLRQ sub-unit homologue of the NADH:ubiquinone oxidoreductase complex), angiogenesis (vascular endothelial growth factor, endothelial PAS domain protein-1, ceruloplasmin, angiopoietin-related protein 2) and cell adhesion/motility (protocadherin 2, cadherin 6, autotaxin, vimentin, lysyl oxidase and semaphorin G). Since some of these genes were overexpressed in 80-90% of RCC tissues, it is important to evaluate their suitability as therapeutic targets.

Biomarkers, Tumor↗

Nicotine intake by snuff users.

Blood nicotine and cotinine concentrations were measured in 27 volunteers before and after taking snuff. Within 10 minutes after snuffing blood nicotine concentrations were comparable to those obtained after the 10 minutes or so that it takes to smoke a cigarette. Nicotine intake from snuffing was related to the experience of the snuffer. In daily and occasional snuffers increases in plasma nicotine concentrations averaged 77.7 and 12.3 nmol/l (12.6 and 2.0 ng/ml) respectively, while the novices showed no appreciable increase. The increase shown by thea daily snuffers was comparable to the average increase of 62.3 nmol/l (10.1 ng/ml) obtained from a single cigarette by a group of heavy smokers. The peak nicotine concentrations in the daily snuffers were also similar to the peak values in 136 heavy smokers--222.6 and 226-3 nmol/l (36.1 and 36.7 ng/ml), respectively. Unusual multiple-dose snuffing produced massive increases in plasma nicotine to concentrations that have never been recorded in smokers. The similarity of the concentrations produced by regular daily snuffing and regular daily smoking suggests that the plasma nicotine concentration has some controlling influence over the self-regulation of these two quite different forms of tobacco use. The rapid absorption of nicotine from snuff confirms its potential as an acceptable and relatively harmless substitute for smoking.

Adolescent↗