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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 | 16S rRNA and 16S to 23S internal transcribed spacer sequence analysisreveal inter and intraspecific Bifidobacteriumphylogeny显示文摘 | Nathalie L B Herve P Irene M | 1996 | lntem J Syst Bacteriology1996，46，： | 1 |
| 3 | Trace of Flicker Sources by Using the Quantity of Flicker Power显示文摘 | Axelberg P G V Bollen M H J Gu Irene Yu-Hua | 2008 | IEEE Trans on Power Delivery2008，23，1： | 1 |
| 4 | 16S rRNA and 16S to 23S internal transcribed spacer sequence analyses reveal inter and intraspecific bifidobacterium phylogeny显示文摘 | LEBLOND-BOURGET N HERVE P IRENE M | 1996 | Int J Syst Bacteriol1996，46，： | 1 |
| 5 | Correlation of tetracycline and sulfonamide antibiotics with corresponding resistance genes and resistant bacteria in a conventional municipal wastewater treatment plant显示文摘 | Gao P Mariya M Irene X | | 0，，： | 1 |
| 6 | 16S rRNA and 16S to 23 S internal transcribed spacer sequence analysis reveal inter and intraspecific Bifidobacterium phylogeny显示文摘 | Nathalie L B Helve P Irene M | 1996 | Intern J Syst Bacteriology1996，46，： | 1 |
| 7 | 16S rRNA to 23S internal transcribed spacer sequence analyses reveal inter - and intraspecific Bifidobacterium phylogeny 显示文摘 | Nathalie L B Herve P Irene M | 1996 | International Journal of Systematic and Evolutionary Microbiology1996，46，1： | 1 |
| 8 | Influences of humic acid, bicarbonate and calcium on Cr(VI) reductive removal by zero- valent iron显示文摘 | LIU T Z RAO P H 1o IRENE M C | 2009 | Sci Total Environ2009，407，： | 1 |
| 9 | 16S rRNA and 16S to 23S internal transcribed spacer sequence analysis reveal inter and inlraspeeific Bifidobaeterium phylogeny 显示文摘 | Nathalie L B Herve P Irene M | 1996 | Int J Sys Baeteriol1996，46，1： | 1 |
| 10 | Valve Repair for Bicuspid Aortic Valve Regurgitation:An Option显示文摘 | Irene M Belen P Pastora G | 2007 | Rev Esp Cardiol2007，60，2： | 1 |
| 11 | Evaluating workflow process designs usingcohesion and coupling metrics 显示文摘 | VANDERFEESTEN IRENE REIJERS H A’ VAN DERAALST W M P | 2008 | Computers in Industry2008，59，5： | 1 |
| 12 | Postinfarction heart failure in rats is associated with upregulation of Glut-1 and down regulation of genes of fatty acid metabolism显示文摘 | Nathalie RV Christophe M Irene P | 2001 | Cardiovasc Res2001，52，4： | 1 |
| 13 | Infectious diseases and risk of leukemia and non-Hodgkin's lymphoma: A case- control study 显示文摘 | Stefano P Irene S Enza M | 2012 | Leuk Res2012，36，11： | 1 |
| 14 | In fluences of humic acid,bicarbonate and calcium on Cr(Ⅵ) reductive removal by zero-valentiron显示文摘 | LIU T Z RAO P H IRENE M C | 2009 | Sci Total Environ2009，407，： | 1 |
| 15 | 16S rRNA and 16S to 23S internal transcribed spacer sequence analysis reveal inter and intraspecific Bifidohacteriumphylogeny显示文摘 | Nathalie L B Herve P Irene M | | 0，，： | 1 |
| 16 | The small GTPase Rab13 regulates assembly of functional tight junctions in epithelial cells显示文摘 | Anne M Irene D Rudy P | 2002 | Mol Biol Cell2002，13，： | 1 |
| 17 | 16s rRNA to 23s intemal- tran scribed spacer sequence analyses reveal inter and interaspe- cific Bidobacterium phlogeny 显示文摘 | Nathalie L B Herve P Iren M | 1996 | Int J Sys Bacterial1996，46，1： | 1 |
| 18 | 16S rRNA to 23S internal transcribed spacer sequence analyses reveal inter-and interaspecific Bidobacterium phylogeny显示文摘 | Nathalie LB Herve P Irene M | 1996 | Int J Sys Bacteriol1996，46，1： | 1 |
| 19 | Design,Synthesis,and Evaluation of Duocarmycin O-Amino Phenol Prodrugs Subject to Tunable Reductive Activation显示文摘 | Lajiness James P Robertson William M Dunwiddie Irene | | 0，，21： | 1 |
| 20 | Lower extremi- ty stiffness: implications for performance and injury显示文摘 | ROBERT J B HARRISON P C IRENE M D | 2003 | Clin Biomech2003，118，6： | 1 |
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