Comprehensive transcriptome studies of cancers often rely on corresponding normal tissue samples to serve as a transcriptional reference. In this study, we performed in-depth analyses of normal kidney tissue transcriptomes from the TCGA and demonstrate that the histological variability in cellularity, inherent in the kidney architecture, lead to considerable transcriptional differences between samples. This should be considered when comparing expression profiles of normal and cancerous kidney tissues. We exploited these differences to define renal-cell-specific gene signatures and used these as a framework to analyze renal cell carcinoma (RCC) ontogeny. Chromophobe RCCs express FOXI1-driven genes that define collecting duct intercalated cells, whereas HNF-regulated genes, specific for proximal tubule cells, are an integral part of clear cell and papillary RCC transcriptomes. These networks may be used as a framework for understanding the interplay between genomic changes in RCC subtypes and the lineage-defining regulatory machinery of their non-neoplastic counterparts.

The objective of this study was to characterize the effects of silver nanoparticles on Pseudomonas aeruginosa. Their interactions with several conventional antibiotics and ability to induce a stress response were examined. Interactions between silver nanoparticles (AgNPs) and antibiotics against free-living cells and biofilm of P. aeruginosa were studied using the chequerboard method and time-kill assays. The ability of AgNPs to induce a stress response was determined by evaluation of cellular levels of the DnaK and HtpG chaperones using SDS-PAGE and Western blot analysis. Synergistic activity against free-living P. aeruginosa between AgNPs and ampicillin, streptomycin, rifampicin and tetracycline, but not oxacillin, ciprofloxacin, meropenem or ceftazidime, was demonstrated by the chequerboard method. No such interactions were observed against P. aeruginosa biofilm. The results of time-kill assays confirmed synergy only for the AgNPs-streptomycin combination. AgNPs induced the expression of chaperone DnaK. No induction of the HtpG chaperone was detected. In conclusion, AgNPs not only display potent bactericidal activity against P. aeruginosa, but also act synergistically with several conventional antibiotics to enhance their effect against free-living bacteria as determined by the chequerboard method. The time-kill assay proved synergy between AgNPs and streptomycin only. The ability of AgNPs to induce the major chaperone protein DnaK may influence bacterial resistance to antimicrobials.

Papillary renal cell carcinoma (pRCC) is the second most common type of renal cell carcinoma. The only curative treatment available for pRCC is radical surgery. If the disease becomes widespread, neither chemo- nor radiotherapy will have therapeutic effect, hence further research on pRCC is of utmost importance. Histologically, pRCC is characterized by a papillary growth pattern with focal aggregation of macrophages of the foam cell phenotype. In other forms of cancer, a clear role for tumor-associated macrophages during cancer growth and progression has been shown. Although the presence of foamy macrophages is a histological hallmark of pRCC tumors, little is known regarding their role in pRCC biology. In order to study the interaction between pRCC tumor and myeloid cells, we established primary cultures from pRCC tissue. We show that human pRCC cells secrete the chemokines IL-8, CXCL16, and chemerin, and that these factors attract primary human monocytes in vitro. RNAseq data from The Cancer Genome Atlas confirmed a high expression of these factors in pRCC tissue. Conditioned medium from pRCC cultures induced a shift in human monocytes toward the M2 macrophage phenotype. In extended cultures, these macrophages became enlarged and loaded with lipids, adopting the foam cell morphology found in pRCC tissue. These results show for the first time that pRCC primary tumor cells secrete factors that attract and differentiate monocytes into anti-inflammatory tumor-associated macrophages with foam cell histology.