RESUMEN
BACKGROUND: Lung cancer remains the leading cause of cancer-related death, largely owing to the lack of effective treatments. A tumour vascular targeting strategy presents an attractive alternative; however, the molecular signature of the vasculature in lung cancer is poorly explored. This work aimed to identify novel tumour vascular targets in lung cancer. METHODS: Enzymatic digestion of fresh tissue followed by endothelial capture with Ulex lectin-coated magnetic beads was used to isolate the endothelium from fresh tumour specimens of lung cancer patients. Endothelial isolates from the healthy and tumour lung tissue were subjected to whole human genome expression profiling using microarray technology. RESULTS: Bioinformatics analysis identified tumour endothelial expression of angiogenic factors, matrix metalloproteases and cell-surface transmembrane proteins. Predicted novel tumour vascular targets were verified by RNA-seq, quantitative real-time PCR analysis and immunohistochemistry. Further detailed expression profiling of STEAP1 on 82 lung cancer patients confirmed STEAP1 as a novel target in the tumour vasculature. Functional analysis of STEAP1 using siRNA silencing implicates a role in endothelial cell migration and tube formation. CONCLUSIONS: The identification of cell-surface tumour endothelial markers in lung is of interest in therapeutic antibody and vaccine development.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/irrigación sanguínea , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/irrigación sanguínea , Neoplasias Pulmonares/genética , Terapia Molecular Dirigida , Neovascularización Patológica/genética , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Femenino , Perfilación de la Expresión Génica , Estudios de Asociación Genética/métodos , Humanos , Pulmón/irrigación sanguínea , Pulmón/metabolismo , Pulmón/patología , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Análisis por Micromatrices , Persona de Mediana Edad , Neovascularización Patológica/tratamiento farmacológico , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ARNRESUMEN
A photometric method for the determination of malathion is described. Malathion dissolved in carbon tetrachloride is hydrolysed at room temperature with sodium ethoxide to dimethyl dithiophosphate (DMDTP) and fumarate. The DMDTP is converted into a molybdenum-DMDTP complex and determined spectrometrically.