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41.
Lorena Rosik Günter Niegisch Ute Fischer Manfred Jung Wolfgang Arthur Schulz Michèle Janine Hoffmann 《Cancer biology & therapy》2014,15(6):742-757
Epigenetic modifiers such as histone deacetylases (HDACs) have come into focus as novel drug targets for cancer therapy due to their functional role in tumor progression. Since common pan-HDAC inhibitors have adverse side effects and minor anti-cancer activity against solid tumors, enzyme-specific inhibitors were developed. HDAC6 is especially well-suited for specific inhibition due to its unique domain structure and mode of action and has been suggested to provide an exceptionally suitable target for cancer therapy. However, expression and function of HDACs have been insufficiently studied in urothelial cancers (UC), a disease urgently requiring new therapeutic approaches. The present study sought to evaluate HDAC6 as a target for treatment of urothelial cancers with enzyme-specific inhibitors. We observed moderate HDAC6 overexpression in urothelial cancer tissues and a broad range of expression in urothelial cancer cell lines. In the cell lines Tubacin was the most potent inhibitor, compared with Tubastatin and ST-80, but still active only at high micromolar concentrations. HDAC6 expression levels correlated poorly with sensitivity to enzyme inhibition. Combined treatments with heat shock, HSP90 inhibition by 17-AAG, proteasome inhibition by bortezomib, or DNA-damaging agents did not result in significant synergistic effects. Experiments with siRNA-mediated knockdown further underlined that urothelial cancer cells do not critically depend on HDAC6 expression for survival. 相似文献
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Lorena Álvarez-Rodríguez Marcos López-Hoyos Eugenio Carrasco-Marín Cristina Mata Jaime Calvo-Alén Elena Aurrecoechea Ricardo Blanco Teresa Ruiz Pedro Muñoz Cacho Ignacio Villa Víctor Manuel Martínez-Taboada 《Reumatología clinica》2012,8(6):321-327
ObjectiveTo investigate whether there is association between the rs20541 (R130Q) polymorphism in the IL-13 gene with disease susceptibility and clinical subsets in patients with elderly-associated inflammatory chronic diseases.Material and methods78 patients with giant cell arteritis (GCA), 174 with polymyalgia rheumatica (PMR), 90 elderly-onset rheumatoid arthritis (EORA), and 465 healthy controls from the same geographic area were studied. The rs20541 (R130Q) polymorphism in the IL-13 gene was evaluated by PCR-RFLP. Circulating levels of IL-13 were measured by ELISA.ResultsA higher frequency of the AA genotype [2.349 (0.994-5.554)], as well as the allele A [1.589 (1.085-2.328] and the A carriers [1.656 (1.021-2.686)] (p < 0.05) was observed in the GCA patients. No significant differences were observed in the PMR and EORA patients as compared with the healthy controls. Neither difference was observed among the different disease groups studied. In GCA patients, differences in the genotype were associated with a worse prognosis. In PMR patients, the AA genotype was associated with higher levels of serum IL-13 than the GA one. However, such an association was not detected for controls and the other disease groups.ConclusionsGCA is more frequent in carriers of the rs20541 (R130Q) polymorphism in the IL-13 gene. The utility of this polymorphism to predict the GCA prognosis must be confirmed in studies with a higher number of patients. 相似文献
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Early pregnancy thyroid hormone reference ranges in Chilean women: the influence of body mass index 下载免费PDF全文
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Wilma Barcellini Anna Zaninoni Anna I. Gregorini Giulia Soverini Lorena Duca Bruno Fattizzo Juri A. Giannotta Patrizia Pedrotti Cristina Vercellati Anna P. Marcello Elisa Fermo Paola Bianchi Maria Domenica Cappellini 《British journal of haematology》2019,185(3):523-531
Iron overload (IO) is poorly investigated in the congenital haemolytic anaemias (CHAs), a heterogeneous group of rare inherited diseases encompassing abnormalities of the erythrocyte membrane and metabolism, and defects of the erythropoiesis. In this study we systematically evaluated routine iron parameters and cardiac and hepatic magnetic resonance imaging, together with erythropoietin, hepcidin, non-transferrin bound iron (NTBI), and cytokine serum levels in patients with different CHAs. We found that 40% of patients had a liver iron concentration (LIC) >4 mg Fe/g dry weight. Hepatic IO was associated with ferritin levels (P = 0·0025), transferrin saturation (TfSat, P = 0·002) and NTBI (P = 0·003). Moreover, ferritin >500 μg/l plus TfSat >60% was demonstrated as the best combination able to identify increased LIC, and TfSat alteration as more important in cases with discordant values. Possible confounding factors, such as transfusions, hepatic disease, metabolic syndrome and hereditary haemochromatosis-associated mutations, had negligible effects on IO. Erythropoietin and hepcidin levels were increased in CHAs compared with controls, correlating with LIC and ferritin, respectively. Regarding cytokines, γ-interferon (IFN-γ) was increased, and both interleukin 6 and IFN-γ levels positively correlated with ferritin and hepcidin levels. Overall, these findings suggest the existence of a vicious cycle between chronic haemolysis, inflammatory response and IO in CHAs. 相似文献
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Andrei Fodor Sara Broggi Elena Incerti Italo Dell’Oca Claudio Fiorino Ana M. Samanes Gajate Marcella Pasetti Mauro G. Cattaneo Paolo Passoni Luigi Gianolli Riccardo Calandrino Maria Picchio Nadia Di Muzio 《Clinical lung cancer》2019,20(1):e29-e38