Taguchi technique of ureteral implantation was used in 22 kidney transplant patients (group T). Group T was compared with 25 patients who were treated using Lich-Gregoir technique (group LG). Immunosuppression, incidence of biopsy evidenced acute cellular rejection (ACR), haematuria rate and ureteral complications (stricture, reflux) were assessed in both groups. The immunosuppression used was based on cyclosporin A (63.6%), tacrolimus (27.3%) and sirolimus (8.1%) in T group. Cyclosporin A(72%), tacrolimus (20%) and sirolimus (8%) were used in LG group. No induction was used. The incidence of ACR was similar in both groups--T resp. LG was 50% resp. 52%. Haematuria after operation was on average 4.0 days in the T group and on average 3.1 in the LG group. Ureteral complications were observed in 18.2% of cases in T group and in 16% of cases in LG group. No reflux was evidenced in any group. Taguchi technique is fast and very easy to do. A slightly higher incidence of ureteralcomplications and a longer period of postoperative haematuria were observed in T group. Taguchi technique is very easily performed with a shorter operating time. We advocate it as a method of ureteral implantation on the thin-wall urinary bladder. The results were very good in these cases.

• MeSH
• imunosupresiva aplikace a dávkování   MeSH
• lidé MeSH
• studie případů a kontrol MeSH
• ureter transplantace   MeSH
• urologické chirurgické výkony metody   škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• klinické zkoušky MeSH

BACKGROUND: We applied a training and testing approach to develop and validate a plasma metabolite panel for the detection of early-stage pancreatic ductal adenocarcinoma (PDAC) alone and in combination with a previously validated protein panel for early-stage PDAC. METHODS: A comprehensive metabolomics platform was initially applied to plasmas collected from 20 PDAC cases and 80 controls. Candidate markers were filtered based on a second independent cohort that included nine invasive intraductal papillary mucinous neoplasm cases and 51 benign pancreatic cysts. Blinded validation of the resulting metabolite panel was performed in an independent test cohort consisting of 39 resectable PDAC cases and 82 matched healthy controls. The additive value of combining the metabolite panel with a previously validated protein panel was evaluated. RESULTS: Five metabolites (acetylspermidine, diacetylspermine, an indole-derivative, and two lysophosphatidylcholines) were selected as a panel based on filtering criteria. A combination rule was developed for distinguishing between PDAC and healthy controls using the Training Set. In the blinded validation study with early-stage PDAC samples and controls, the five metabolites yielded areas under the curve (AUCs) ranging from 0.726 to 0.842, and the combined metabolite model yielded an AUC of 0.892 (95% confidence interval [CI] = 0.828 to 0.956). Performance was further statistically significantly improved by combining the metabolite panel with a previously validated protein marker panel consisting of CA 19-9, LRG1, and TIMP1 (AUC = 0.924, 95% CI = 0.864 to 0.983, comparison DeLong test one-sided P= .02). CONCLUSIONS: A metabolite panel in combination with CA19-9, TIMP1, and LRG1 exhibited substantially improved performance in the detection of early-stage PDAC compared with a protein panel alone.

• MeSH
• duktální karcinom slinivky břišní genetika   metabolismus   patologie   MeSH
• invazivní růst nádoru MeSH
• lidé MeSH
• metabolom * MeSH
• mucinózní adenokarcinom genetika   metabolismus   patologie   MeSH
• nádorové biomarkery krev   genetika   MeSH
• nádory slinivky břišní genetika   metabolismus   patologie   MeSH
• následné studie MeSH
• papilární karcinom genetika   metabolismus   patologie   MeSH
• staging nádorů MeSH
• studie případů a kontrol MeSH
• transkriptom * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Electrochemical conversion of fesoterodine to one of its oxidation products was evaluated with the application of the wall-jet flow cell. A traditional, "static" mode of electrolysis was compared with the "dynamic" mode of cell performance. For statistical assessment of the data, experiments were planned and performed with the application of design of experiments approach, namely Taguchi L18 design. After screening phase, the experimental settings were broadened or adjusted according to the results and optimization was performed. All of the samples were electrolysed with the use of chronoamperometric method in a three electrode system. The electrolysed samples were analysed using UHPLC-PDA-QDA method. The chromatographic run was performed in gradient elution with the application of C8 column. The response was expressed as % area of the main peak found with the PDA detection method whereas QDA detector was used in positive SIM mode for structural confirmation. All data obtained for both screening and optimization were treated together and linear models were adjusted. The use of large-surface glassy carbon electrode along with pH~7 were found to be the most significant factors influencing electrochemical oxidation of fesoterodine in both modes. The major differences were identified in terms of voltage applied to the electrodes which yielded the highest amounts of oxidation product. Evolution of electrochemical methods may serve as complementary technique in stress degradation studies in pharmaceutical industry.

• MeSH
• benzhydrylové sloučeniny MeSH
• elektrochemické techniky MeSH
• elektrody MeSH
• elektrolýza * MeSH
• oxidace-redukce MeSH
• výzkumný projekt * MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND & AIMS: Chromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy by unclear mechanisms. Expression of the colon cancer-associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer enabling characteristic. METHODS: We performed cytogenetic analysis of colorectal cancer (CRC) cell lines (HCT116, KM12C/SM, and HT29) overexpressing CCAT2 and colon organoids from C57BL/6N mice with the CCAT2 transgene and without (controls). CRC cells were also analyzed by immunofluorescence microscopy, γ-H2AX, and senescence assays. CCAT2 transgene and control mice were given azoxymethane and dextran sulfate sodium to induce colon tumors. We performed gene expression array and mass spectrometry to detect downstream targets of CCAT2 lncRNA. We characterized interactions between CCAT2 with downstream proteins using MS2 pull-down, RNA immunoprecipitation, and selective 2'-hydroxyl acylation analyzed by primer extension analyses. Downstream proteins were overexpressed in CRC cells and analyzed for CIN. Gene expression levels were measured in CRC and non-tumor tissues from 5 cohorts, comprising more than 900 patients. RESULTS: High expression of CCAT2 induced CIN in CRC cell lines and increased resistance to 5-fluorouracil and oxaliplatin. Mice that expressed the CCAT2 transgene developed chromosome abnormalities, and colon organoids derived from crypt cells of these mice had a higher percentage of chromosome abnormalities compared with organoids from control mice. The transgenic mice given azoxymethane and dextran sulfate sodium developed more and larger colon polyps than control mice given these agents. Microarray analysis and mass spectrometry indicated that expression of CCAT2 increased expression of genes involved in ribosome biogenesis and protein synthesis. CCAT2 lncRNA interacted directly with and stabilized BOP1 ribosomal biogenesis factor (BOP1). CCAT2 also increased expression of MYC, which activated expression of BOP1. Overexpression of BOP1 in CRC cell lines resulted in chromosomal missegregation errors, and increased colony formation, and invasiveness, whereas BOP1 knockdown reduced viability. BOP1 promoted CIN by increasing the active form of aurora kinase B, which regulates chromosomal segregation. BOP1 was overexpressed in polyp tissues from CCAT2 transgenic mice compared with healthy tissue. CCAT2 lncRNA and BOP1 mRNA or protein were all increased in microsatellite stable tumors (characterized by CIN), but not in tumors with microsatellite instability compared with nontumor tissues. Increased levels of CCAT2 lncRNA and BOP1 mRNA correlated with each other and with shorter survival times of patients. CONCLUSIONS: We found that overexpression of CCAT2 in colon cells promotes CIN and carcinogenesis by stabilizing and inducing expression of BOP1 an activator of aurora kinase B. Strategies to target this pathway might be developed for treatment of patients with microsatellite stable colorectal tumors.

• MeSH
• aurora kinasa B metabolismus   MeSH
• azoxymethan toxicita   MeSH
• chemorezistence genetika   MeSH
• chromozomální nestabilita * MeSH
• cytogenetické vyšetření MeSH
• dextrany toxicita   MeSH
• experimentální nádory chemicky indukované   genetika   patologie   MeSH
• genový knockdown MeSH
• karcinogeneze genetika   MeSH
• kolon cytologie   patologie   MeSH
• kolorektální nádory chemicky indukované   genetika   patologie   MeSH
• lidé MeSH
• myši transgenní MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• organoidy MeSH
• primární buněčná kultura MeSH
• proteiny vázající RNA genetika   metabolismus   MeSH
• protokoly protinádorové kombinované chemoterapie farmakologie   terapeutické užití   MeSH
• protoonkogenní proteiny c-myc metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• RNA dlouhá nekódující genetika   metabolismus   MeSH
• signální transdukce genetika   MeSH
• střevní sliznice cytologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

• MeSH
• patologie MeSH
• podpůrné srdeční systémy MeSH
• umělé srdce MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• kardiologie
• patologie