microRNAs (miRNA) are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Here, we profiled the expression of 290 unique human miRNAs in 11 normal and 106 bladder tumor samples using spotted locked nucleic acid-based oligonucleotide microarrays. We identified several differentially expressed miRNAs between normal urothelium and cancer and between the different disease stages. miR-145 was found to be the most down-regulated in cancer compared with normal, and miR-21 was the most upregulated in cancer. Furthermore, we identified miRNAs that significantly correlated to the presence of concomitant carcinoma in situ. We identified several miRNAs with prognostic potential for predicting disease progression (e.g., miR-129, miR-133b, and miR-518c*). We localized the expression of miR-145, miR-21, and miR-129 to urothelium by in situ hybridization. We then focused on miR-129 that exerted significant growth inhibition and induced cell death upon transfection with a miR-129 precursor in bladder carcinoma cell lines T24 and SW780 cells. Microarray analysis of T24 cells after transfection showed significant miR-129 target downregulation (P = 0.0002) and pathway analysis indicated that targets were involved in cell death processes. By analyzing gene expression data from clinical tumor samples, we identified significant expression changes of target mRNA molecules related to the miRNA expression. Using luciferase assays, we documented a direct link between miR-129 and the two putative targets GALNT1 and SOX4. The findings reported here indicate that several miRNAs are differentially regulated in bladder cancer and may form a basis for clinical development of new biomarkers for bladder cancer. [Cancer Res 2009;69(11):4851-60]

MicroRNAs (miRNA) are small noncoding RNAs commonly deregulated in cancer. The miR-200 family (miR-200a, -200b, -200c, -141 and -429) MicroRNAs (miRNA) are a class of $22nt noncoding RNAs that regulate gene expression post-transcriptionally.1 It is widely accepted that miRNA expression is broadly altered in most forms of cancer, 2 and loss of miR-200 family (miR200a, -200b, -200c, -141 and-429) expression has been reported in several types of advanced carcinoma, including bladder cancer. 3,4 Recently, several independent reports have implicated miR-200 and miR-205 in epithelial to mesenchymal transition (EMT), an important event in tumorigenesis associated with a decrease in E-cadherin levels, loss of cell adhesion and subsequent tumor invasion and metastasis. 5-9The miR-200s and miR-205 are key determinators of the epithelial phenotype by directly targeting ZEB1 (also known as TCF8) and ZEB2 (also known as SIP-1), which are transcriptional repressors of E-cadherin (CDH1). Loss of miR-200 expression thus leads to accumulation of ZEB1 and ZEB2, which is sufficient to silence CDH1 and promote EMT and tumor invasion. Interestingly, ZEB1 has been shown to act as a transcriptional repressor of miR-200c and miR-141 by directly interacting with E-and/or Z-box motifs in the miR-200c-141 promoter through a double-negative feedback mechanism. 8,9 However, the mechanisms regulating miR-200 and miR-205 expression remain otherwise largely uncharacterized. A recent study also concluded that ZEB1 is necessary for development and maintenance of stemness in cancer cells, thereby

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Cobas h 232 point-of-care instrument for measurement of NT-proBNP performed satisfactorily with regard to precision, user-friendliness, and lot-variation. A decrease in NT-proBNP levels observed in samples transported to a central laboratory needs further attention and investigation.

Excellent concordance was observed between the screening and confirmatory tests, fibrin structure analysis and fibrinogen gene analysis. Fibrin structure analysis should be considered in the laboratory algorithm for diagnosis of dysfibrinogenemia.