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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 | Genetic Variation in IL28B Is Associated With Chronic Hepatitis C and Treatment Failure: A Genome-Wide Association Study显示文摘 | Andri Rauch Zoltán Kutalik Patrick Descombes Tao Cai Julia Di Iulio Tobias Mueller Murielle Bochud Manuel Battegay Enos Bernasconi Jan Borovicka Sara Colombo Andreas Cerny Jean–Fran?ois Dufour Hansjakob Furrer Huldrych F. Günthard Markus Heim Bernard Hirs | 2010 | Gastroenterology2010，，4： | 2 |
| 3 | Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice显示文摘 | Debra A Cockayne Sara G | 2000 | Nature2000，10，407： | 1 |
| 4 | Genomic and transcriptomic analysis of the AP2/ERF superfamily in Vitis vinifera显示文摘 | FRANCESCO L FEDERICO G SARA Z | 2010 | BMC Genomics2010，11，： | 1 |
| 5 | A new cost-effec- tive polymeric film containing an Eu (III) complex acting as UV protector and down-converter for Si-based solar cells and modules显示文摘 | Tania M H Joaquin S Sara G P | 2015 | Solar Energy Materials and Solar Cells2015，136，： | 1 |
| 6 | Characterization of Transcriptional Complexity during Berry Development in Vitis vinifera Using RNA-Seq显示文摘 | Sara Z Alberto F Enrico G | 2010 | Plant Physiology2010，，152： | 1 |
| 7 | Chemicals and biological prod-ucts used in south - east Asian shrimp farming,and theirpotential impact on the environment - a review 显示文摘 | Sara G Bengt - Erik B | 2001 | SciTotal Environ2001，280，： | 1 |
| 8 | Chemicals and biological products used in south-east Asian shrimp farming,and their potential impact on the environment-a review显示文摘 | Bengt-Erik B | 2001 | Sci Total Environ2001，280，： | 1 |
| 9 | A New Classification System Predictive of Complications in Surgically Treated Pediatric Humeral Lateral Condyle Fractures 显示文摘 | Jennifer MW Sara G Scott Y | 2009 | J Pediatr Orthop2009，29，6： | 1 |
| 10 | Worries and concerns experienced by urse specialists during inter-hospital transports of critically ill patients:A critical incident study显示文摘 | Marcus G Sara W Bengt F | 2010 | Intensive and Critical Care Nurs-ing2010，26，1： | 1 |
| 11 | Regenerative endodontic treatment(revascularization)of immature necrotic molars medicated with calcium hydroxide:Acase series显示文摘 | Cehreli ZC Isbitiren B Sara S Erbas G | 2011 | Journal of endodontics2011，37，9： | 1 |
| 12 | Alterations inendocannabinoid tone following chemotherapy -inducedperipheral neuropathy: effects of endocannabinoiddeactivation inhibitors targeting fatty -acid amidehydrolase and monoacylglycerol lipase in comparison toreference analgesics following cisplatin treatment 显示文摘 | JOSEE G YVONNE L SARA M | 2013 | Pharmacol Res2013，67，1： | 1 |
| 13 | Persistent defects in transmitter release and synapsin phosphorylation in cerebral ortex after transient moderate ischemic injury显示文摘 | Bolay H Gürsoy-(o)zdemir Y Sara Y | 2002 | Stroke2002，33，： | 1 |
| 14 | Advanced electron microscopy for advanced materials显示文摘 | VAN TENDELOO G SARA B VAN AERT S | 2012 | Advanced Materi- als2012，24，42： | 1 |
| 15 | Arsenic and heavy metal uptake and accumulation in native plant species from soils polluted by mining activities显示文摘 | SARA G S DAVID G C MA ANGELES Q N | 2012 | Water Air & Soil Pollution2012，223，2： | 1 |
| 16 | Characterization of polyploid wheat genomic diversity using a high-density 90 000 single nucleotide polymorphism array 显示文摘 | Wang SC Debbie W Kerrie F Alexandra A Shiaoman C Bevan EH Marco M Silvio S Sara GM Luigi C Anna MM Alex W Stuart S Gary B Ralf W Joerg P International Wheat Genome Sequencing Consortium Morten L Diane M Rudi A Rudy D Gina BG Abraham K Alina RA Catherine F Jerome S Michele M Curtis P Luo MC Jan DMM Jorge D Martin G Roberto T Cindy L Ivan M Colin C Keith JE Matthew H Eduard A | 2014 | Plant Biotechnol J2014，12，： | 1 |
| 17 | Growth of Mytilus galloprovincialis ( mollusca, bivalvia) close to fish farms:a case of integrated multi-trophic aquaculture within the Tyrrhenian Sea显示文摘 | Sara G Zenone A Tomasello A | 2009 | Hydrobiologia2009，636，1： | 1 |
| 18 | The Multidimensional Scale of Perceived Social Support 显示文摘 | Gregory D Zimet Nancy W Dahlem Sara G Zimet | 1988 | J Pers Assess1988，52，1： | 1 |
| 19 | Changes in the expression of melatonin receptors induced by melatonin treatment in hepatocarcinoma HepG2 cells显示文摘 | Sara C P Javier M R Andres G P | 2009 | J Pineal Res2009，47，2： | 1 |
| 20 | Predicitive and protective factors associated with upper gastrointestinal bleeding after percutaneons coronary intervention: a case control study显示文摘 | Chin MW Yong G Bul sara MK | 2007 | Am J Gastroenterol2007，102，11： | 1 |
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