Assuntos
Hipertrigliceridemia/sangue , Hipertrigliceridemia/diagnóstico , Terapia Combinada , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Diagnóstico Diferencial , Dieta com Restrição de Gorduras , Humanos , Hiperlipoproteinemia Tipo IV/sangue , Hiperlipoproteinemia Tipo IV/diagnóstico , Hiperlipoproteinemia Tipo IV/epidemiologia , Hiperlipoproteinemia Tipo IV/terapia , Hipertrigliceridemia/epidemiologia , Hipertrigliceridemia/terapia , Estilo de Vida , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/epidemiologia , Valores de Referência , Fatores de Risco , Triglicerídeos/sangueRESUMO
Raf kinase plays a central role in oncogenic signaling and acts as a downstream effector of Ras in the extracellular signal-regulated (ERK) kinase pathway. BAY 43-9006 (BAY) is a novel signal transduction inhibitor that prevents tumor cell proliferation and angiogenesis through blockade of the Raf/MEK/ERK pathway at the level of Raf kinase and the receptor tyrosine kinases vascular endothelial growth factor receptor-2 and platelet-derived growth factor receptor-beta. The present study evaluates the effects of combining BAY and platinum derivatives on human colorectal cancer cells using different incubation protocols. Our data show that the combination of oxaliplatin or cisplatin with BAY results in marked antagonism irrespective of the used application schedule. Furthermore, BAY abrogates the cisplatin-induced G2 arrest as well as the G1 arrest induced by oxaliplatin. BAY alone arrests cancer cells in their current cell cycle phase and affects cell cycle regulative genes. Specifically, BAY reduced the protein expression of p21Cip1 as well as cyclin D1, and inhibits the expression of cdc2 (cdk1). Utilizing atom absorption spectrometry, BAY significantly reduced cellular uptake of platinum compounds and thereby the generation of DNA adducts. Taken together, co-incubation with BAY results in reduced cellular uptake of platinum compounds and consecutively reduced generation of DNA adducts, and eventually decreased cellular cytotoxicity in human colorectal cancer cells. Our results indicate that the Raf kinase inhibitor BAY 43-9006 might also directly or indirectly interact with platinum transporter proteins in vitro.
Assuntos
Antineoplásicos/farmacologia , Benzenossulfonatos/farmacologia , Cisplatino/farmacologia , Compostos Organoplatínicos/farmacologia , Piridinas/farmacologia , Quinases raf/antagonistas & inibidores , Antineoplásicos/farmacocinética , Western Blotting , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/antagonistas & inibidores , Linhagem Celular Tumoral , Cisplatino/farmacocinética , Ciclina D1/antagonistas & inibidores , Inibidor de Quinase Dependente de Ciclina p21 , Adutos de DNA/antagonistas & inibidores , Antagonismo de Drogas , Humanos , Niacinamida/análogos & derivados , Compostos Organoplatínicos/farmacocinética , Compostos de Fenilureia , Piridinas/farmacocinética , SorafenibeRESUMO
In this investigation thallium contents in soil and plants in the EuroRegion Neisse were analysed and the distribution determined. The median top-soil content is 0.5 mg/kg in the area investigated. In this low-contaminated area the moss Pleurozium schreberi contains 0.04-0.13 microg/g and the moss Polytrichumformosum between 0.01 and 0.05 microg/g Tl. The effects of thallium on man and the terrestrial environment were examined. In an epidemiological study a significant positive correlation was found between the thallium content of the two mosses and the incidence of diseases of the circulatory system. The LOEC for thallium in bioassays with terrestrial invertebrates and plants in artificial soil ranged from 1 to 500 mg/kg, which indicates an toxicity of thallium up to 100 times higher than that of Cadmium.
