Expression of miRNA-106b in conventional renal cell carcinoma is a potential marker for prediction of early metastasis after nephrectomy

<p>Abstract</p> <p>Background</p> <p>MicroRNAs are endogenously expressed regulatory noncoding RNAs. Previous studies have shown altered expression levels of several microRNAs in renal cell carcinoma.</p> <p>Methods</p> <p>We examined the expression levels of selected microRNAs in 38 samples of conventional renal cell carcinoma (RCC) and 10 samples of non-tumoral renal parenchyma using TaqMan real-time PCR method.</p> <p>Results</p> <p>The expression levels of miRNA-155 (p < 0.0001), miRNA-210 (p < 0.0001), miRNA-106a (p < 0.0001) and miRNA-106b (p < 0.0001) were significantly over-expressed in tumor tissue, whereas the expression of miRNA-141 (p < 0.0001) and miRNA-200c (p < 0.0001) were significantly decreased in RCC samples. There were no significant differences between expression levels of miRNA-182 and miRNA-200b in tumor samples and renal parenchyma. Our data suggest that expression levels of miRNA-106b are significantly lower in tumors of patients who developed metastasis (p = 0.030) and miR-106b is a potential predictive marker of early metastasis after nephrectomy in RCC patients (long-rank p = 0.032).</p> <p>Conclusions</p> <p>We have confirmed previous observations obtained by miRNA microarray analysis using standardized real-time PCR method. For the first time, we have identified a prognostic significance of miRNA-106b, which, after validation on a larger group of patients, maybe useful as a promising biomarker in patients with RCC.</p

Krajinně-ekologické‚ vodohospodářské‚ ekonomické a legislativní hodnocení záměru výstavby kanálu Dunaj - Odra - Labe:Vliv potenciální výstavby kanálu Dunaj - Odra - Labe na biodiverzitu lužních lesů

Orientační ekologická charakteristika ekosystémů lužních lesů v ČR, které by byly dotčeny potenciální výstavbou vodního kanálu DOL. Stručné shrnutí dosavadních poznatků o vlhkostním režimu půd lužních lesů a vlivu vodohospodářských úprav na ekosystémy lužních lesů

Decreased expression levels of PIWIL1, PIWIL2, and PIWIL4 are associated with worse survival in renal cell carcinoma patients

Robert Iliev,1,2 Michal Stanik,3 Michal Fedorko,4 Alexandr Poprach,1 Petra Vychytilova-Faltejskova,1,2 Katerina Slaba,2 Marek Svoboda,1 Pavel Fabian,5 Dalibor Pacik,1 Jan Dolezel,2 Ondrej Slaby3,4 1Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, 2Central European Institute of Technology, Masaryk University, 3Department of Urologic Oncology, Masaryk Memorial Cancer Institute, 4Department of Urology, University Hospital Brno, Masaryk University Brno, 5Department of Diagnostic and Experimental Pathology, Masaryk Memorial Cancer Institute, Brno, Czech RepublicAbstract: Piwi-interacting RNAs (piRNAs) are a newly discovered class of small non-coding RNAs involved in silencing of transposable elements and in sequence-specific chromatin modifications. PIWI proteins (PIWIL) belong to the family of Argonaute genes/proteins, bind piRNAs and their functioning have been described mainly in germ-line cells and more recently also in stem cells and cancer cells. There are four PIWI proteins PIWIL1, PIWIL2, PIWIL3, and PIWIL4 discovered in human till now. Recent studies suggested that deregulated the expression of Piwi proteins and selected piRNAs is common to many types of cancers. We found significantly lower expression of PIWIL1 (P&lt;0.0001) and piR-823 (P=0.0001) in tumor tissue in comparison to paired renal parenchyma. Further, we observed progressive decrease in PIWIL1 (P=0.0228), PIWIL2 (P=0.0015), and PIWIL4 (P=0.0028) expression levels together with increasing clinical stage. PIWIL2 (P=0.0073) and PIWIL4 (P=0.0001) expression progressively decreased also with increasing Fuhrman grade. Most importantly, low-expression levels of PIWIL1 (P=0.009), PIWIL2 (P&lt;0.0001), and PIWIL4 (P=0.0065) were significantly associated with worse overall survival in renal cell carcinoma (RCC) patients. Our results suggest the involvement of PIWIL genes and piR-823 in RCC pathogenesis, and indicate PIWIL1, PIWIL2, and PIWIL4 as potential prognostic biomarkers in patients with RCC. Keywords: kidney cancer, PIWIL, piRN

Sequential therapy with bevacizumab and EGFR inhibitors for metastatic colorectal carcinoma: a national registry-based analysis

Tomas Buchler,1 Renata Chloupkova,2 Alexandr Poprach,3 Ondrej Fiala,4,5 Igor Kiss,3 Katerina Kopeckova,6 Ladislav Dusek,2 Veronika Veskrnova,1 Lubomir Slavicek,7 Milan Kohoutek,8 Jindrich Finek,4 Marek Svoboda,3 Lubos Petruzelka,9 Bohuslav Melichar10 1Department of Oncology, First Faculty of Medicine, Charles University and Thomayer University Hospital, 140 59 Prague, Czech Republic; 2Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic; 3Department of Comprehensive Cancer Care and Faculty of Medicine, Masaryk Memorial Cancer Institute and Masaryk University, Brno 656 53, Czech Republic; 4Department of Oncology, University Hospital, 304 60 Pilsen, Czech Republic; 5Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic; 6Department of Oncology, Motol University Hospital and Second Faculty of Medicine, Charles University, 150 00 Prague, Czech Republic; 7Department of Oncology, Jihlava Hospital Comprehensive Cancer Centre, Jihlava, Czech Republic; 8Department of Oncology, T Bata Hospital and Comprehensive Cancer Centre, Zlin, Czech Republic; 9Department of Oncology, General University Hospital and Charles University First Faculty of Medicine, 128 08 Prague, Czech Republic; 10Department of Oncology, Palacky University Medical School and Teaching Hospital, 775 20 Olomouc, Czech Republic Purpose: Although inhibitors of vascular endothelial growth factor and inhibitors of epidermal growth factor receptor (EGFRi) are commonly used for the treatment of metastatic colorectal cancer (mCRC), the optimal sequencing of these agents is currently unclear. Methods: A national registry of targeted therapies was used to analyze baseline &shy;characteristics and outcomes of patients with mCRC and wild-type KRAS exon 2 status who received &shy;bevacizumab and EGFRi (cetuximab or panitumumab) as a part of first- and second-line &shy;treatment in either sequence. Results: The cohort included 490 patients (181 patients treated with first-line EGFRi and second-line bevacizumab and 309 patients treated with first-line bevacizumab and second-line EGFRi). Median overall survival (OS) from the initiation on first-line therapy was similar for patients treated with either sequence, reaching 31.8 (95% CI 27.5&ndash;36.1) vs 31.4 months (95% CI 27.8&ndash;35.0) for EGFRi &rarr; bevacizumab vs bevacizumab &rarr; EGFRi cohort, respectively. Time from first-line initiation to progression on the second-line therapy [progression-free survival (PFS)] was 21.1 (95% CI 19.3&ndash;23.0) vs 19.3 months (95% CI 17.3&ndash;21.3) for bevacizumab &rarr; EGFRi vs EGFRi &rarr; bevacizumab cohort, respectively (P=0.016). Conclusion: This retrospective analysis of real-world data of patients with wild-type KRAS exon 2 mCRC showed no differences in OS between cohorts treated with bevacizumab &rarr; EGFRi vs the reverse sequence while combined PFS favored the bevacizumab &rarr; EGFRi sequence. Keywords: colorectal carcinoma, bevacizumab, panitumumab, cetuximab, sequenc