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| 1 | Preclinical evaluation of azathioprine plus buthionine sulfoximine in the treatment of human hepatocarcinoma and colon carcinoma显示文摘AIM: To evaluate the efficacy and the safety of azathioprine (AZA) and buthionine sulfoximine (BSO) bylocalized application into HepG2 tumor in vivo.METHODS: Different hepatoma and colon carcinoma cell lines (HepG2, HuH7, Chang liver, LoVo, RKO, SW-48, SW-480) were grown in minimal essencial medium supplemented with 10% fetal bovine serum and 1% antibiotic/antimycotic solution and maintained in a humidified 37 ℃ incubator with 5% CO2. These cells were pretreated with BSO for 24 h and then with AZA for different times. We examined the effects of this combination on some proteins and on cellular death. We also studied the eff icacy and the safety of AZA (6 mg/kg per day) and BSO (90 mg/kg per day) in HepG2 tumor growth in vivo using athymic mice. We measured safety by serological markers such as aminotransferases and creatine kinase.RESULTS: The in vitro studies revealed a new mechanism of action for the AZA plus BSO combination in the cancer cells compared with other thiopurines (6-mercaptopurine, 6-methylmercaptopurine, 6-thioguanine and 6-methylthioguanine) in combination with BSO. The cytotoxic effect of AZA plus BSO in HepG2 cells resulted from necroptosis induction in a mitochondrial-dependent manner. From kinetic studies we suggest that glutathione (GSH) depletion stimulates c-Jun amino-terminal kinase and Bax translocation in HepG2 cells with subsequent deregulation of mitochondria (cytochrome c release, loss of membrane potential), and proteolysis activation leading to loss of membrane integrity, release of lactate dehydrogenase and DNA degradation. Some of this biochemical and cellular changes could be reversed by N-acetylcysteine (a GSH replenisher). In vivo studies showed that HepG2 tumor growth was inhibited when AZA was combined with BSO.CONCLUSION: Our studies suggest that a combination of AZA plus BSO could be useful for localizedtreatment of hepatocellular carcinoma as in the currently used transarterial chemoembolization method. | Borja Hernández-Breijo Jorge Monserrat Sara Ramírez-Rubio Eva P Cuevas Diana Vara Inés Díaz-Laviada M Dolores Fernández-Moreno Irene D Román Javier P Gisbert Luis G Guijarro | 2011 | World Journal of Gastroenterology2011，17，34： | 2 |
| 2 | Microbiological air quality in tie-stall dairy barns and some factors that influence it显示文摘 | SILVANA P CRISTIN B EVA ANDREA D | 2011 | Af J Agric Res2011，6，32： | 1 |
| 3 | Oxidative elimination of cyanotoxins : comparison of ozone, chlorine, chlorine dioxide and permanganate显示文摘 | RODRIGUEZ EVA ONSTAD GRETCHEN D KULL TOMAS P J | 2007 | Water Research2007，41，15： | 1 |
| 4 | Rapid determination of volatile compounds in grapes by HS-SPME coupled with GC-MS显示文摘 | Consuelo D M Soledad P C | 2005 | Talanta2005，66，5： | 1 |
| 5 | Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside 显示文摘 | Eva P P Cile D G Richard K | | Nature0，426，11： | 1 |
| 6 | Barrier coatings for type C/SiC ceramic-matrix composites (Review) 显示文摘 | SARKISOV P D POPOVICH N V ORLOVA L A ANAN'EVA Y E | 2008 | Glass and Ceramics2008，65，： | 1 |
| 7 | Determination of biogenic amines in foods using ultra-performance liquid chromatography 显示文摘 | Eva D Martin K Tamara P | 2009 | Food Chemistry2009，116，2： | 1 |
| 8 | Rapid determination of volatile compounds in grapes by HS-SPME coupled with GC-MS显示文摘 | Eva S P Consuelo D M Soledad P C | 2005 | Talanta2005，66，5： | 1 |
| 9 | Comparative karyology of species of the genera Misgurnus and Cobitis ( Cobitidae ) from the Amur River basin in connection with their taxonomic relations and the evolution of karyotypes显示文摘 | VASIL' EV V P VASIL' EVA E D | 2008 | Journal of Ichthyology2008，48，1： | 1 |
| 10 | Study of the strawberry cell endo-β- (1,4)-glucanase protein accumulation and characterization of its in vitro activity by beterologous expression in Pichia pastoris 显示文摘 | XAVIER P EVA D P MIQUEL V et ai | 2004 | Plant Science2004，167，： | 1 |
| 11 | Rapid determination of volatile compounds in grapes by HS-SPME coupled with GC–MS显示文摘 | Eva Sánchez-Palomo M. Consuelo Díaz-Maroto M. Soledad Pérez-Coello | 2005 | Talanta2005，，5： | 1 |
| 12 | A Systematic Review of the Diagnostic Accuracy of Natriuretic Peptides for Heart Failure 显示文摘 | Jenny A D Paul P G Eva P | 2004 | Arch Intern Med2004，164，18： | 1 |
| 13 | Antiviral activity of bovine type ill interferon against foot-and-mouth disease virus显示文摘 | Fayna D S Marcelo W Eva P | 2011 | Virology2011，413，2： | 1 |
| 14 | Rapid determination of volatile compounds in grapes by HS-SPME coupled with GC-MS显示文摘 | Eva S P Consuelo D M Soledad P C | 2005 | Talanta2005，66，5： | 1 |
| 15 | Rapid determination of volatile compounds in grapes by HS-SPME coupled with GC-MS显示文摘 | Eva S P Consuelo D M Soledad P C | 2005 | Talanta2005，66，5： | 1 |
| 16 | Structure of mitochondrial ADP/ATP carrier in complex with earboxyatractyloside显示文摘 | Eva P P Cile D G Richard K | | 0，，6962： | 1 |
| 17 | Systemic corticosteroids for community-acquired pneumonia:Reasons for use and lack of benefit on outcome显示文摘 | Eva P Catia C Povilas D | | 0，，02： | 1 |
| 18 | Hydrolytic hydrogenation of hemicellulose over metal modified mesoporous catalyst显示文摘 | Bright T. Kusema Laura Faba Narendra Kumar P?ivi M?ki-Arvela Eva Díaz Salvador Ordó?ez Tapio Salmi Dmitry Yu. Murzin | 2012 | Catalysis Today2012，，1： | 1 |
| 19 | Refractive change in hyperglycaemia: hyperopia, not myopia 显示文摘 | EVA P R PASCOE P T VAUGHAN D G | 1982 | Br J Ophthalmol1982，66，8： | 1 |
| 20 | Social Satisfacion, Commuting and Neighborhoods显示文摘 | Elizabeth C D Eva H Thomas P | 2013 | Journal of Transport Geography2013，30，6： | 1 |
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