RESUMEN
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.
Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma de Células Renales/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/genética , Northern Blotting , Adhesión Celular , Supervivencia Celular , Cartilla de ADN , ADN de Neoplasias/genética , Humanos , Neovascularización Patológica , Hibridación de Ácido Nucleico , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , Células Tumorales CultivadasRESUMEN
Oxidative stress appears to have a central role in the induction of apoptosis following the exposure of cells to a range of cytotoxic insults. The modulation of apoptosis by a diverse range of antioxidants has been reported in many systems. We demonstrate, for the first time, the anti-apoptotic properties of the antioxidant, 4b, 5,9b,10-tetrahydroindeno[1,2-b]indole (THII), in Jurkat T cells subjected to a number of cytotoxic insults. THII was found to inhibit the morphological features of apoptosis in cells treated with the cytotoxic agents camptothecin, actinomycin D and ultraviolet (UV) irradiation. However, THII was unable to inhibit apoptosis induced by anti-Fas IgM. Peroxide and superoxide anion production following UV treatment was monitored, and THII was found to only partially inhibit superoxide anion production. THII was unable to inhibit mitochondrial depolarization in UV, Camptothecin or anti-Fas-treated cells. Further downstream, THII exibited strong inhibition of caspase-3 activation in UV, but not in anti-Fas-treated cells. These results suggest that THII may exert its effects downstream of mitochondrial depolarization, but upstream of caspase-3 activation.
Asunto(s)
Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Indoles/farmacología , Mitocondrias/fisiología , Linfocitos T/patología , Caspasa 3 , Inhibidores de Caspasas , Activación Enzimática/efectos de los fármacos , Humanos , Células Jurkat , Potenciales de la Membrana , Transducción de Señal/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Linfocitos T/fisiologíaAsunto(s)
Color , Nicotina/análisis , Humo/análisis , Breas/análisis , Femenino , Humanos , MasculinoRESUMEN
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.
Asunto(s)
Nicotiana , Nicotina/sangre , Plantas Tóxicas , Tabaco sin Humo , Adolescente , Adulto , Anciano , Cotinina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fumar , Factores de TiempoRESUMEN
The Medical Data Base System provides a mechanism for correlating industrial hygiene survey data with specific jobs and with the medical records of the individual employee. An occupational survey groups jobs by departments or by location according to potential exposures. Results of industrial hygiene surveys are correlated with the occupational survey to assign exposures. Results of pre-placement health examinations, given to every employee and periodic examinations, given to those employees who are potentially exposed to harmful chemical or physical agents in their work environment, form the Medical Records File. Development of the data collection and storage phase of this system was completed in 1972, and the system was implemented at that time. The retrieval/analysis phase of the system is currently under development. Although the present data base does not provide an adequate basis for true epidemiological studies, some trial evaluations have been completed successfully.