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Clear cell renal cell carcinoma (ccRCC) comprises more than 80% of all renal cancers and when metastasized leads to a 5-year survival rate of only 10%. The high rate of therapy failure and resistance development calls for reliable methods that provide information on the actionable biological pathways and predict optimal treatment protocols for individual patients. We here applied targeted RNA sequencing (t/RNA-NGS) using single molecule Molecular Inversion Probes on tumor nephrectomy samples of five ccRCC patients, comparing tumor with healthy kidney tissues. Transcriptome profiling focused on expression of genes with involvement in ccRCC biology that can be targeted with clinically available drugs. Results confirm high expression of vascular endothelial growth factor-A (VEGF-A) in tumor tissue relative to healthy-appearing kidney, in line with the angiogenic nature of ccRCC. PDGFRα and KIT, targets of the multi-kinase inhibitor sunitinib which is one of the current choices of first-line drug in metastasized ccRCC patients, were expressed at relatively low levels in tumor tissues, whereas significantly increased in normal kidney. Of all measured druggable tyrosine kinases, MET, AXL, or EGFR were expressed at higher levels in tumors than in normal kidney tissues, although intertumor differences were observed. Using cancer cell lines we show that t/RNA-NGS gene expression profiles can be used to predict in vitro sensitivity to targeted drugs. In conclusion, t/RNA-NGS analysis may provide insights into the (druggable) molecular make-up of individual renal cancers, and may guide personalized therapy of renal cell cancers. [ABSTRACT FROM AUTHOR]

This article argues that the police are a particularly interesting public institution to study with respect to the incorporation of diversity within organizations. It is the first in presenting empirical data on diversity in a wide selection of police forces in Europe, which leads to the conclusion that the general level of diversity (defined in terms of gender, migrant background, and sexual orientation) is low and diminishes as police officers’ rank increases, although changes can be observed during the last decade. In a search for answers, the article offers a brief overview of academic literature in the field of police diversity policies, and identifies two important research gaps: most studies do not touch upon all three relevant policy areas (i.e. recruitment, retention, and promotion), and comparative studies are rare. Given these findings, a comprehensive view is proposed that might structure future comparative studies. [ABSTRACT FROM PUBLISHER]