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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 | A novel methodology for the monitoring of the agricultural production process based on wireless sensor networks显示文摘 | Soledad Escolar Díaz Jesús Carretero Pérez Alejandro Calderón Mateos Maria-Cristina Marinescu Borja Bergua Guerra | 2011 | Computers and Electronics in Agriculture2011，，2： | 2 |
| 3 | Deorbit Process Using Solar Radiation Force显示文摘 | BORJA J A TUN D | 2006 | Journal of Spacecraft & Rockets2006，43，3： | 1 |
| 4 | Overview of integrative tools and methods in assessing ecological integrity in estuarine and coastal systems worldwide显示文摘 | BORJA A BRICKER S B DAUER D M | 2008 | Marine Pollution Bulletin2008，56，： | 1 |
| 5 | Subspace identification for industrial process 显示文摘 | Borjas S D M Garcia C | 2011 | Tema Tend Mat Appl Comput2011，12，3： | 1 |
| 6 | Structural control considering soil-structure interaction effects 显示文摘 | Smith H D Wu W H Borja R I | 1994 | Earthquake Engineering and Structural Dynamics1994，23，： | 1 |
| 7 | Polychlorinated biphenyls and their biodegradation 显示文摘 | BORJA J TALEON D M AURESENIA J | 2005 | Process Biochemistry2005，40，6： | 1 |
| 8 | Triptolide therapy for neuroblastoma decreases cell viability in vitro and inbhibits tumor growth in vivo 显示文摘 | Antonoff MB Chugh R Borja - Cacho D | 2009 | Surgery2009，15，2： | 1 |
| 9 | Hepatolithiasis with secondary cholangitis and supernumerary left hepatic lobe 显示文摘 | LAVENANT -BORJA MI FERNANDEZ -RIVERO J PACHUCA-GONZALEZ D | 2013 | Ann Hepatol2013，12，6： | 1 |
| 10 | Polychlorinated biphenyls and their biodegradation 显示文摘 | Borja J Taleon D M Auresenia J | 2005 | Process Biochemistry2005，40，6： | 1 |
| 11 | High-performance capillary electrophoretic method for the quantification of 5-methyl 2-deoxycytidine in genomic DNA, application to plant, animaland human cancer tissues显示文摘 | Fraga M F Uriol E Borja D L | 2002 | Electrophoresis2002，23，： | 1 |
| 12 | Transanal Total Mesorectal Excision in Rectal Cancer: Short-term Outcomes in Comparison With Laparoscopic Surgery显示文摘 | María Fernández-Hevia Salvadora Delgado Antoni Castells Marta Tasende Dulce Momblan Gabriel Díaz del Gobbo Borja DeLacy Jaume Balust Antonio M. Lacy | 2015 | Annals of Surgery2015，，2： | 1 |
| 13 | Fertility, pregnancy outcomes and deliveries following myomectomy: experience of a French Caribbean University Hospital 显示文摘 | Borja de Mozota D Kadhel P | 2014 | Arch Gynecol Obstet2014，289，3： | 1 |
| 14 | Polychlorinated biphenyls and their biedegradation显示文摘 | Borja J Taleon D M Auresenia J | 2005 | Process Biochemistry2005，40，6： | 1 |
| 15 | Overview ofintegrative tools and methods in assessing ecological integ-rity in estuarine and coastal systems worldwide 显示文摘 | Borja A Bricker S B Dauer D M | 2008 | MarPoll Bull2008，56，9： | 1 |
| 16 | Overview of integrative tools and methods in assessing ecological integrity in estuarine and coastal systems worldwide显示文摘 | BORJA A BRICKER S B DAUER D M | 2008 | Marine Pollution Bulletin2008，56，9： | 1 |
| 17 | Assessing the environmental quality status in estuarine and coastal systems: Comparing methodologies and indices显示文摘 | BORJA A DAUER D M | 2008 | Ecological Indicators2008，8，4： | 1 |
| 18 | Polychlorinated biphenyls and their biodegradation显示文摘 | Borja J Taleon D M Auresenia J | 2005 | Process Biochemistry2005，40，： | 1 |
| 19 | A novel methodology for the monitoring of the agricultural production process based on wireless sensor networks显示文摘 | Soledad Escolar Díaz Jesús Carretero Pérez Alejandro Calderón Mateos Maria-Cristina Marinescu Borja Bergua Guerra | 2011 | Computers and Electronics in Agriculture2011，，2： | 1 |
| 20 | Polyacrylic Acid ( poly-A ) as a chelant and dispersant显示文摘 | Kuila D Blay G A Borjas R E | 1999 | J Appl Polym Sci1999，73，7： | 1 |
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