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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 | Meta-analysis:Comparative efficacy of different proton-pump inhibitors in triple therapy for Helicobacter pylori eradication显示文摘 | Vergara M Vallve M Gisbert J P | 2003 | Aliment Pharmacol Ther2003，18，： | 1 |
| 3 | The Yeast HAL1 Gent: Improves Salt Tolerance of Transgenic Tomato显示文摘 | Gisbert C Rus A M Bolarin M C | 2000 | Plant Physiol2000，123，1： | 1 |
| 4 | Two-week, high- dose proton pump inhibitor, moxifloxacin triple Helicobacter oylori therapy after failure of standard triple or non-bismuth quadruple treatments 显示文摘 | Gisbert JP Romano M Molina-Infante J | 2015 | Digestive and Liver Disease2015，47，2： | 1 |
| 5 | Hyperlipidemia in liver transplant recipients: Prevalence and risk factors显示文摘 | C Gisbert M Prieto M Berenguer M Breto D Carrasco J u de J Mir J Berenguer | 1997 | Liver Transplantation1997，，4： | 1 |
| 6 | The yeast HAL 1 gene improves salt tolerance of transgenic tomato显示文摘 | Gisbert C Rus A M Bolarin M C | 2000 | Plant Physiol2000，123，： | 1 |
| 7 | Evaluation of three different tests for the detection of stool antigens to diagnose Helicobacter pylori infection in patients with upper gastrointestingal bleeding显示文摘 | Gisbert JP Trapero M Galvet Y | 2004 | Aliment Pbarmacol Tber2004，19，8： | 1 |
| 8 | A protein linkage map of the ESAT-6 secretion system I(ESX-1 ) of Mycobacterium tuberculosis显示文摘 | Janka T Gisbert S Ute M L | 2009 | Microbiological Research2009，164，： | 1 |
| 9 | Value of quantitative serology for confirmation of Hellcobacter pylori eradication :an 18-month follow-up study 显示文摘 | GISBERT J P BLANCO M BENITO L M | 2000 | Clin Infect Dis2000，30，10： | 1 |
| 10 | Functional characterization of al-adrenoceptor subtypes in vascular tissues using different experimental approaches: a comparative study显示文摘 | Gisbert R Madrero Y Sabino V Noguera M A Ivorra M D D'Ocon P | 2003 | Br J Pharmacol2003，138，： | 1 |
| 11 | Review article:Hehcobacter Pytori 'rescue'regimen when proton pump inhibitor based triple therapies fail 显示文摘 | GISBERT J P PAJARES J M | 2002 | Aliment Pharmacol Ther2002，16，6： | 1 |
| 12 | Firstline triple therapy with levofloxacin for Helicobacter pylori eradi cation显示文摘 | Gisbert JP Fernandez-Bermejo M Molina-Infante J | 2007 | Aliment Pharmacol Ther2007，26，3： | 1 |
| 13 | The yeast HALl gene improves salt tolerance of transgenic tomato 显示文摘 | Gisbert C Rus A M Bolarin M C | 2000 | Plant Physiol2000，123，1： | 1 |
| 14 | Disease severity in familial cases of IBD显示文摘 | M. Andreu L. Márquez E. Domènech J.P. Gisbert V. García I. Marín-Jiménez M. Pe?alva F. Gomollón X. Calvet O. Merino E. Garcia-Planella N. Vázquez-Romero M. Esteve P. Nos A. Gutiérrez I. Vera J.L. Cabriada M.D. Martín A. Ca?as-Ventura J. Panés | 2014 | Journal of Crohn’s and Colitis2014，，3： | 1 |
| 15 | Experimental studies on the structure and mechanical properties of multi-layer and angle-interlock woven structures 显示文摘 | Chen X Spola M Gisbert Paya J | 1999 | Journal of the Textile Institute1999，90，1： | 1 |
| 16 | Phenotypic concordance in familial inflammatory bowel disease (IBD). Results of a nationwide IBD Spanish database显示文摘 | Eduard Cabré Míriam Ma?osa Valle García-Sánchez Ana Gutiérrez Elena Ricart Maria Esteve Jordi Guardiola Mariam Aguas Olga Merino Angel Ponferrada Javier P. Gisbert Esther Garcia-Planella Gloria Ce?a José L. Cabriada Miguel Montoro Eugeni Domènech | 2013 | Journal of Crohn’s and Colitis2013，，： | 1 |
| 17 | The yeast HAL1 gene improves salt tolerance of transgenic tomato 显示文摘 | Gisbert C Rus A M Bolarin M C Lopez-Coronado J M Arrillaga I Montesinos C Caro Manuel Serrano R Moreno V | 2000 | Plant Physiol2000，123，： | 1 |
| 18 | Fourth- line rescue therapy with rifahutin in patients with three Helicobacterpylori eradication failures显示文摘 | GISBERT JP CASTRO-FERMANDEZ M PEREZ-AISA A et a/ | 2012 | Aliment Pharmacol Ther2012，35，： | 1 |
| 19 | Liver injury in in- flammatory bowel disease : long - term follow - up study of 786 patients 显示文摘 | Gisbert JP Luna M Gonza'lez - Lama Y | 2007 | Inflammatory Bowel Diseases2007，13，： | 1 |
| 20 | Analysis behaviour of static and dynamic properties of ethylene-pro- pylene-diene-methylene crumb rubber mortar显示文摘 | GISBERT A N BORRELL J M G GARCiA F P | 2014 | Construc- tion and Building Materials2014，50，： | 1 |
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