BACKGROUND: Yolk sac tumor (YST) is a germ cell tumor. It is primarily located in the gonads but can also occur extragonadally (extragonadal yolk sac tumor - EGYST), most commonly in the pelvis, retroperitoneum or mediastinum. Only a few YSTs of the urachus have been described. CASE REPORT: We present a rare case report of a 37-year-old male with episodes of macroscopic hematuria. The histological specimen obtained by transurethral resection showed a solid, and in some parts papillary infiltrative, high-grade tumor with numerous areas of marked nuclear atypia and clear invasion between the detrusor bundles. Glandular pattern has been observed in only minority of the tumor. Immunohistochemistry showed significant positivity for GPC3, SALL4 and cytokeratins AE1/AE3, while KRT7 and GATA3 were negative. We concluded that the biopsy findings were consistent with urothelial carcinoma with infrequent YST differentiation. In definitive surgical specimens we found a malignant epithelial, glandular and cystically arranged tumor of germinal appearance arising from urachus. The surrounding urothelium was free of invasive or in situ tumor changes. We reclassified the tumor as a urachal YST. CONCLUSION: EGYST was suspected because glandular and hepatoid structures were found, but the presence of these structures should be verified by immunohistochemistry.

• MeSH
• dospělí MeSH
• lidé MeSH
• nádor z entodermálního sinusu diagnóza   metabolismus   patologie   MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory močového měchýře diagnóza   metabolismus   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH

Little attention was given to the interaction between tumor and stromal cells in urothelial bladder carcinoma (UBC). While recent studies point towards the existence of different fibroblast subsets, no comprehensive analyses linking different fibroblast markers to UBC patient survival have been performed so far. Through immunohistochemical analysis of five selected fibroblast markers, namely alpha smooth muscle actin (ASMA), CD90/Thy-1, fibroblast activation protein (FAP), platelet derived growth factor receptor-alpha and -beta (PDGFRa,-b), this study investigates their association with survival and histopathological characteristics in a cohort of 344 UBC patients, involving both, muscle-invasive and non-muscle-invasive cases. The data indicates that combinations of stromal markers are more suited to identify prognostic patient subgroups than single marker analysis. Refined stroma-marker-based patient stratification was achieved through cluster analysis and identified a FAP-dominant patient cluster as independent marker for shorter 5-year-survival (HR(95% CI)2.25(1.08-4.67), p = 0.030). Analyses of interactions between fibroblast and CD8a-status identified a potential minority of cases with CD90-defined stroma and high CD8a infiltration showing a good prognosis of more than 80% 5-year-survival. Presented analyses point towards the existence of different stroma-cell subgroups with distinct tumor-modulatory properties and motivate further studies aiming to better understand the molecular tumor-stroma crosstalk in UBC.

• MeSH
• aktiny metabolismus   MeSH
• antigeny Thy-1 metabolismus   MeSH
• CD8-pozitivní T-lymfocyty cytologie   imunologie   metabolismus   MeSH
• fenotyp MeSH
• fibroblasty cytologie   metabolismus   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé MeSH
• membránové proteiny metabolismus   MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory močového měchýře metabolismus   mortalita   patologie   MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• růstový faktor odvozený z trombocytů - receptor alfa metabolismus   MeSH
• senioři MeSH
• serinové endopeptidasy metabolismus   MeSH
• shluková analýza MeSH
• želatinasy metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The specific effects of sodium selenite (selenite) on a chemoresistant human bladder cancer cell line RT-112/D21 were investigated during 72 h. Selenite at low concentration of 2.5 μmol (otherwise tolerated in normal urothelial cells UROtsa) suppressed growth and proliferation of the tested cancer cells via induced oxidative stress. Selenite further altered mitochondrial functions (i.e. decreased mitochondrial membrane potential, increased production of superoxide and reduced ATP synthesis), disrupted lysosomal membranes and activated autophagy. These changes in selenite-exposed cells ultimately resulted in their demise via necrosis and other cell death modality displaying heterotypic apoptotic and autophagic features.

• MeSH
• apoptóza účinky léků   MeSH
• autofagie účinky léků   MeSH
• buněčná smrt účinky léků   MeSH
• chemorezistence účinky léků   MeSH
• lidé MeSH
• lyzozomy účinky léků   metabolismus   MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• mitochondrie účinky léků   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory močového měchýře farmakoterapie   metabolismus   patologie   MeSH
• proliferace buněk účinky léků   MeSH
• seleničitan sodný farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Extra-hepatic metabolism of xenobiotics by epithelial tissues has evolved as a self-defence mechanism but has potential to contribute to the local activation of carcinogens. Bladder epithelium (urothelium) is bathed in excreted urinary toxicants and pro-carcinogens. This study reveals how differentiation affects cytochrome P450 (CYP) activity and the role of NADPH:P450 oxidoreductase (POR). CYP1A1 and CYP1B1 transcripts were inducible in normal human urothelial (NHU) cells maintained in both undifferentiated and functional barrier-forming differentiated states in vitro. However, ethoxyresorufin O-deethylation (EROD) activity, the generation of reactive BaP metabolites and BaP-DNA adducts, were predominantly detected in differentiated NHU cell cultures. This gain-of-function was attributable to the expression of POR, an essential electron donor for all CYPs, which was significantly upregulated as part of urothelial differentiation. Immunohistology of muscle-invasive bladder cancer (MIBC) revealed significant overall suppression of POR expression. Stratification of MIBC biopsies into "luminal" and "basal" groups, based on GATA3 and cytokeratin 5/6 labeling, showed POR over-expression by a subgroup of the differentiated luminal tumors. In bladder cancer cell lines, CYP1-activity was undetectable/low in basal PORlo T24 and SCaBER cells and higher in the luminal POR over-expressing RT4 and RT112 cells than in differentiated NHU cells, indicating that CYP-function is related to differentiation status in bladder cancers. This study establishes POR as a predictive biomarker of metabolic potential. This has implications in bladder carcinogenesis for the hepatic versus local activation of carcinogens and as a functional predictor of the potential for MIBC to respond to prodrug therapies.

• MeSH
• buněčná diferenciace MeSH
• čipová analýza tkání MeSH
• cytochrom P-450 CYP1A1 genetika   MeSH
• cytochrom P450 CYP1B1 genetika   MeSH
• down regulace MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory močového měchýře genetika   metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• urotel cytologie   metabolismus   MeSH
• xenobiotika farmakologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• adipokiny izolace a purifikace   metabolismus   MeSH
• cytokiny izolace a purifikace   metabolismus   MeSH
• diabetes mellitus 2. typu * epidemiologie   etiologie   komplikace   MeSH
• gastrointestinální nádory etiologie   komplikace   metabolismus   MeSH
• hyperglykemie komplikace   krev   metabolismus   MeSH
• hyperinzulinismus komplikace   krev   metabolismus   MeSH
• insulinu podobný růstový faktor I MeSH
• komplikace diabetu etiologie   metabolismus   MeSH
• leptin izolace a purifikace   metabolismus   MeSH
• lidé MeSH
• nádory endometria etiologie   komplikace   metabolismus   MeSH
• nádory ledvin etiologie   komplikace   metabolismus   MeSH
• nádory močového měchýře etiologie   komplikace   metabolismus   MeSH
• nádory prsu etiologie   komplikace   metabolismus   MeSH
• nádory * epidemiologie   etiologie   metabolismus   MeSH
• nehodgkinský lymfom etiologie   komplikace   metabolismus   MeSH
• obezita epidemiologie   etiologie   komplikace   MeSH
• statistika jako téma MeSH
• tuková tkáň * enzymologie   metabolismus   sekrece   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

PURPOSE: To assess the role of N-cadherin as a prognostic biomarker in patients with non-muscle-invasive bladder cancer (NMIBC) treated with transurethral resection with or without adjuvant intravesical therapy. PATIENTS AND METHODS: Immunohistochemistry using monoclonal mouse antibody was used to evaluate the expression status of N-cadherin in 827 patients with NMIBC. N-cadherin was considered positive if any immunoreactivity with membranous staining was detected. Multivariable Cox regression models were performed to evaluate the prognostic effect of N-cadherin on survival outcomes. RESULTS: N-cadherin expression was observed in 333 patients (40.3%); it was associated with pT1 stage and high tumor grade (both were P<0.001). Median follow-up was 55 months (interquartile range: 18-106). On multivariable Cox regression analyses that adjusted for the effect of the standard clinicopathologic features, N-cadherin expression remained associated with recurrence-free survival (P = 0.007) but not progression-free survival (P = 0.3), cancer-specific survival (P = 0.2), or overall survival (P = 0.9). Adding N-cadherin to a model for prediction of disease recurrence modestly improved its discrimination from 72.8% to 73.4%. CONCLUSION: N-cadherin is expressed in approximately 2/5 patients with NMIBC. Its expression is associated with adverse pathological features and higher risk of disease recurrence but not progression. N-cadherin could be incorporated in predictive tools to assist in recurrence prediction helping thereby in patient selection regarding adjuvant therapies and follow-up planning.

• MeSH
• invazivní růst nádoru MeSH
• kadheriny metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru metabolismus   MeSH
• míra přežití MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory močového měchýře metabolismus   patologie   terapie   MeSH
• následné studie MeSH
• přežití bez známek nemoci MeSH
• progrese nemoci MeSH
• retrospektivní studie MeSH
• senioři MeSH
• staging nádorů MeSH
• stupeň nádoru MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

We have investigated the cytotoxicity and specific effects of selenite in human bladder cancer cell line RT-112 and its clonogenic variant RT-112 HB. Selenite inhibited cell growth and proliferation in both cell lines. Treated cells developed extensive vacuolization which was dose independent but occurring in differing time frames. Ultrastructure analysis revealed that the observed vacuoles are damaged mitochondria and potentially other subcellular compartments. Selenite-specific effects on mitochondria were further confirmed by mitochondrial membrane potential analysis, changes in ATP production and generation of superoxide. Simultaneously, selenite induced DNA damage in treated cells with activation of p53, PARP-1 and JNK and suppressed autophagy. Cells ultimately died via a combination of apoptosis, necrosis and a distinct type of cell death featuring "vacuolar shrinkage", loss of adherence and absence of secondary necrosis as well as other classical markers of either apoptosis or autophagy. The significant presence of so called necroptosis was also not confirmed as the specific inhibitor necrostatin-1 could not prevent cell death. These results thus confirm the toxicity of selenite in bladder cancer cells while pointing at potentially new mechanism of action of this compound in this model.

• MeSH
• apoptóza účinky léků   MeSH
• kyselina seleničitá toxicita   MeSH
• lidé MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• mitochondrie účinky léků   fyziologie   MeSH
• nádorové buněčné linie MeSH
• nádorový supresorový protein p53 metabolismus   MeSH
• nádory močového měchýře metabolismus   patologie   MeSH
• nekróza chemicky indukované   MeSH
• poškození DNA * MeSH
• superoxidy metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The histopathological structure of malignant tumours involves two essential compartments - the tumour parenchyma with the actual transformed cells, and the supportive tumour stroma. The latter consists of specialized mesenchymal cells, such as fibroblasts, macrophages, lymphocytes and vascular cells, as well as of their secreted products, including components of the extracellular matrix, matrix modifying enzymes and numerous regulatory growth factors and cytokines. In consequence, the tumour stroma has the ability to influence virtually all aspects of tumour development and progression, including therapeutic response. AIM: In this article we review the current knowledge of tumor stroma interactions in urothelial carcinoma and present various experimental systems that are currently in use to unravel the biological basis of these heterotypic cell interactions. RESULTS: For urothelial carcinoma, an extensive tumour stroma is quite typical and markers of activated fibroblasts correlate significantly with clinical parameters of advanced disease. Another clinically important variable is provided by the stromal expression of syndecan-1. CONCLUSION: Integration of markers of activated stroma into clinical risk evaluation could aid to better stratification of urothelial bladder carcinoma patients. Elucidation of biological mechanisms underlying tumour-stroma interactions could provide new therapeutical targets.

• MeSH
• biologické modely MeSH
• lidé MeSH
• mezibuněčná komunikace MeSH
• nádorové mikroprostředí * MeSH
• nádorové proteiny metabolismus   MeSH
• nádory močového měchýře metabolismus   patologie   MeSH
• urotel metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH

Cancer is a major public health problem worldwide. In the United States alone, 1 in 4 deaths is due to cancer and for 2013 a total of 1,660,290 new cancer cases and 580,350 cancer-related deaths are projected. Comprehensive profiling of multiple cancer genomes has revealed a highly complex genetic landscape in which a large number of altered genes, varying from tumor to tumor, impact core biological pathways and processes. This has implications for therapeutic targeting of signaling networks in the development of treatments for specific cancers. The NFκB transcription factor is constitutively active in a number of hematologic and solid tumors, and many signaling pathways implicated in cancer are likely connected to NFκB activation. A critical mediator of NFκB activity is TGFβ-activated kinase 1 (TAK1). Here, we identify TAK1 as a novel interacting protein and target of fibroblast growth factor receptor 3 (FGFR3) tyrosine kinase activity. We further demonstrate that activating mutations in FGFR3 associated with both multiple myeloma and bladder cancer can modulate expression of genes that regulate NFκB signaling, and promote both NFκB transcriptional activity and cell adhesion in a manner dependent on TAK1 expression in both cancer cell types. Our findings suggest TAK1 as a potential therapeutic target for FGFR3-associated cancers, and other malignancies in which TAK1 contributes to constitutive NFκB activation.

• MeSH
• apoptóza MeSH
• buněčná adheze MeSH
• fosforylace MeSH
• imunoprecipitace MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• MAP kinasy kinas (kinas) genetika   metabolismus   MeSH
• messenger RNA genetika   MeSH
• mnohočetný myelom genetika   metabolismus   patologie   MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádorové buňky kultivované MeSH
• nádory močového měchýře genetika   metabolismus   patologie   MeSH
• NF-kappa B genetika   metabolismus   MeSH
• peptidové fragmenty MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• proliferace buněk MeSH
• receptor fibroblastových růstových faktorů, typ 3 genetika   metabolismus   MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• signální transdukce MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• stanovení celkové genové exprese MeSH
• techniky dvojhybridového systému MeSH
• transformující růstový faktor beta genetika   metabolismus   MeSH
• tyrosin metabolismus   MeSH
• western blotting MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: To evaluate the prognostic value of T1 subclassification and fascin-1 expression in T1 human urothelial cell carcinoma of the bladder. MATERIALS AND METHODS: In a prospective study with 105 consecutive patients, T1 tumors were subclassified into 2 groups according to the depth of tumor invasion. The tunica muscularis mucosae was used as a landmark. The expression of fascin-1 was examined by using an anti-fascin-1 mouse monoclonal antibody and was evaluated semiquantitatively for both intensity and distribution. The patients were followed up for 27.3 +/- 13.7 months. RESULTS: The T1 tumor subclassification was feasible in 99 patients (94%). T1a tumor was detected in 77 patients (73%), T1b tumor in 22 patients (21%). An invasive tumor was found in 5 patients (4.8%) during the restaging transurethral resection of the bladder. The risk of understaging in patients with T1b tumor was 18%. There was not a significant difference in time to the recurrence in the T1a and the T1b group. The progression-free survival rates were significantly different between both groups (p = 0.0034). No correlation was found between fascin-1 positivity and the depth of tumor invasion. Fascin-1 positivity did not correlate with recurrence or the progression-free intervals. In the multivariate analysis, only the extent of lamina propria invasion was an independent predictor of the tumor progression. The fascin positivity was not an independent prognostic factor relating to the risk of recurrence or progression. CONCLUSION: The finding of T1b tumor was connected with a significantly higher risk of progression and understaging. The fascin-1 expression did not correlate with the depth of tumor invasion or with the tumor recurrence or progression. 2008 S. Karger AG, Basel.

• MeSH
• analýza přežití MeSH
• dospělí MeSH
• financování organizované MeSH
• hodnocení rizik MeSH
• imunohistochemie MeSH
• interval spolehlivosti MeSH
• invazivní růst nádoru genetika   patologie   MeSH
• karcinom z přechodných buněk genetika   metabolismus   mortalita   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru genetika   mortalita   MeSH
• mikrofilamentové proteiny genetika   metabolismus   MeSH
• nádorové biomarkery analýza   genetika   MeSH
• nádory močového měchýře genetika   metabolismus   mortalita   patologie   MeSH
• odds ratio MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• prospektivní studie MeSH
• regulace genové exprese u nádorů MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• transportní proteiny genetika   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• randomizované kontrolované studie MeSH