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We investigated expression profiles of microRNA (miRNA) in renal cell carcinoma [clear cell carcinomas (CCC) and chromophobe renal cell carcinomas (ChCC)] and in normal kidneys by using a miRNA microarray platform which covers a total of 470 human miRNAs (Sanger miRBase release 9.1). Unsupervised hierarchical cluster analysis revealed that CCC and ChCC were separable and that no subgroups were identified in CCCs. We found that 43 miRNAs were differentially expressed between CCC and normal kidney, of which 37 were significantly down-regulated in CCC and the other 6 were up-regulated. We also found that 57 miRNAs were differentially expressed between ChCC and normal kidney, of which 51 were significantly down-regulated in ChCC and the other 6 were up-regulated. Together, these observations indicate that expression of miRNAs tends to be down-regulated in both CCC and ChCC compared with normal kidney. We observed that miR-141 and miR-200c were the most significantly down-regulated miRNAs in CCCs. Indeed, in all cases of CCC analysed, both miR-141 and miR-200c were down-regulated in comparison with normal kidney. Microarray data and quantitative RT-PCR showed that these two miRNAs were expressed concordantly. TargetScan algorithm revealed that ZFHX1B mRNA is a hypothetical target of both miR-141 and -200c. We established by quantitative RT-PCR that, in CCCs in which miR-141 and miR-200c were down-regulated, ZFHX1B, a transcriptional repressor for CDH1/E-cadherin, tended to be up-regulated. Furthermore, we found that overexpression of miR-141 and miR-200c caused down-regulation of ZFHX1B and up-regulation of E-cadherin in two renal carcinoma cell lines, ACHN and 786-O. On the basis of these findings, we suggest that down-regulation of miR-141 and miR-200c in CCCs might be involved in suppression of CDH1/E-cadherin transcription via up-regulation of ZFHX1B. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We analysed chromosomal copy number aberrations (CNAs) in renal cell carcinomas by array-based comparative genomic hybridization, using a genome-wide scanning array with 2304 BAC and PAC clones covering the whole human genome at a resolution of roughly 1.3 Mb. A total of 30 samples of renal cell carcinoma were analysed, including 26 cases of clear cell carcinoma (CCC) and four cases of chromophobe renal cell carcinoma (ChCC). In CCCs, gains of chromosomes 5q33.1-qter (58%), 7q11.22-q35 (35%) and 16p12.3-p13.12 (19%), and losses of chromosomes 3p25.1-p25.3 (77%), 3p21.31-p22.3 (81%), 3p14.1-p14.2 (77%), 8p23.3 (31%), 9q21.13-qter (19%) and 14q32.32-qter (38%) were detected. On the other hand, the patterns of CNAs differed markedly between CCCs and ChCCs. Next, we examined the correlation of CNAs with expression profiles in the same tumour samples in 22/26 cases of CCC, using oligonucleotide microarray. We extracted genes that were differentially expressed between cases with and without CNAs, and found that significantly more up-regulated genes were localized on chromosomes 5 and 7, where recurrent genomic gains have been detected. Conversely, significantly more down-regulated genes were localized on chromosomes 14 and 3, where recurrent genomic losses have been detected. These results revealed that CNAs were correlated with deregulation of gene expression in CCCs. Furthermore, we compared the patterns of genomic imbalance with histopathological features, and found that loss of 14q appeared to be a specific and additional genetic abnormality in high-grade CCC. When we compared the expression profiles of low-grade CCCs with those of high-grade CCCs, differentially down-regulated genes tended to be localized on chromosomes 14 and 9. Thus, it is suggested that copy number loss at 14q in high-grade CCC may be involved in the down-regulation of genes located in this region. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of recombinant α2binterferon therapy on natural killer (NK) activity and antibody-dependent cell-mediated cytotoxicity (ADCC) in the peripheral blood in patients with renal cell carcinoma who had undergone radical nephrectomy. Patients and methods Between January 1988 and June 1989, 20 patients (14 men and six women, mean age 59 years, range 43-80) received interferon (IFN) therapy following radical nephrectomy for renal cell carcinoma. Thirteen patients had stage I disease, one had stage II and six had stage III; none had metastases. Results There was a significant increase in NK activity at 5 and 7 months after starting IFN therapy but there was no increase in ADCC. Conclusions Low doses of IFN administered long-term increased NK activity in patients with renal cell carcinoma. This finding should be helpful in designating protocols for randomized studies of post-operative IFN administration as adjuvant therapy. [ABSTRACT FROM AUTHOR]

Four-week-old Wistar strain rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) solution for 12 weeks and used as a precancerous model. Sixteen-week-old rats of the same strain were used as controls. Plasma membranes (PMs) were prepared from normal and precancerous bladder epithelium. The lipid content and the fatty acid compositions of total lipids, phospholipids, and their subclasses were analysed. The following observations were made: 1) Precancerous PMs had longer chains composed of more unsaturated fatty acids than the normal ones. 2) There were high amounts of arachidonic acid in rat bladder epithelium, and it accounted for more than fifty percent of phosphatidylethanolamine. PMs of precancerous epithelium had more arachidonic acid than those of the normal epithelium. These findings may be useful for the early detection of precancerous epithelium. [ABSTRACT FROM AUTHOR]