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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 | Numerical investigation of NOx emissions from a tangentially-fired utility boiler under conventional and overfire air operation显示文摘 | LUIS I D CRISTOBAL C JAVIER P | 2007 | Fuel2007，87，7： | 1 |
| 3 | Emotional and neutral declarative memory impairments and associated white matter microstructural abnormalities in adults with type 2 diabetes 显示文摘 | YAU P L JAVIER D TSUI W | 2009 | Psychiatry Research2009，174，： | 1 |
| 4 | Chilling of drought-hardened and no-hardened plants of different chilling-sensitive maize lineschanges in water relations and ABA contents显示文摘 | Javier P D Jose I J Manuel S D | 1997 | Plant Sci1997，122，： | 1 |
| 5 | Chilling of drought-hardened and no-hardened plants of different chilling-sensitive maize lines-changes in water relations and ABA content显示文摘 | Javier P D Jose I J Manuel S D | 1997 | Plant Sciences1997，122，： | 1 |
| 6 | Rejection after conversion to a proliferation signal inhibitor in chronic heart transplantation显示文摘 | Francisco González‐Vílchez José A. Vázquez de Prada María J. Paniagua Luis Almenar Sonia Mirabet Manuel Gómez‐Bueno Beatriz Díaz‐Molina Jose M. Arizón Juan Delgado Félix Pérez‐Villa María G. Crespo‐Leiro Luis Martínez‐Dolz Eulalia Roig Javier Segovia José | 2013 | Clin Transplant2013，，6： | 1 |
| 7 | Detection of plasmid-mediated AmpC β-lactamase genes in clinical isolates by using multiplex PCR显示文摘 | Javier Pérez-Pérez F Nancy D Hanson | 2002 | J Clin Microbiol2002，，： | 1 |
| 8 | Transistor paint:high mobilities in small bandgap polymer semiconductor based on the strong acceptor,diketopyrrolopyrrole and strong donor,dithienopyrrole显示文摘 | Toby L N Tomasz M Y Jun Y L Mishra S P Belot J A Balliet C L Javier A E Kowalewski T McCullough R D | 2010 | Advanced Materials2010，22，41： | 1 |
| 9 | The CHEK2 1100delC allele is not relevant for risk assessment in HNPCC and HBCC Spanish families显示文摘 | Ana Sánchez de Abajo Miguel de la Hoya Javier Godino Vicente Furió Alicia Tosar Pedro Pérez-Segura Eduardo Díaz-Rubio Trinidad Caldés | 2005 | Familial Cancer2005，，2： | 1 |
| 10 | Emotional and neutral declarative memory impairments and associated white matter microstructural abnormalities in adults with type 2 diabetes显示文摘 | Yau P L Javier D Tsui W | 2009 | Psychiat Res2009，174，3： | 1 |
| 11 | Numerical investigation of NOx emissions from a tangentially-fired utility boiler under conventional and overfire air operation显示文摘 | Luis D Cristobal C Javier P | 2008 | Fuel2008，87，7： | 1 |
| 12 | Relevance of insulin-like growth factor 1 receptor gene expression as a prognostic factor in non-small-cell lung cancer显示文摘 | M. Teresa Agulló-Ortu?o C. Vanesa Díaz-García Alba Agudo-López Carlos Pérez Ana Cortijo Luis Paz-Ares Fernando López-Ríos Francisco Pozo Javier de Castro Hernán Cortés-Funes José A. López Martín | 2015 | Journal of Cancer Research and Clinical Oncology2015，，： | 1 |
| 13 | Chilling of drought-hard- ened and non-hardened plants of different chilling-sensitive maize lines changes in water relations and ABA contents 显示文摘 | Javier P de J Jose I J Manuel S D | 1997 | Plant Science1997，122，1： | 1 |
| 14 | Separa- tion of the sp3 and sp2 Components in the Cls Photoemis- sion Spectra of Amorphous Carbon Films 显示文摘 | JAVIER D GUIDO P SALVADOR F | 1996 | Physical Review B1996，54，11： | 1 |
| 15 | Detection of plasmidmediated AmpC β-lactamase genes in clinical isolates by using multiplex PCR显示文摘 | F Javier Pérez-Pérezl Nancy D Hansonl | 2002 | J Clin Microbiol2002，40，6： | 1 |
| 16 | Numerical prediction of unburned carbon levels in large pulverized coal utility boilers显示文摘 | Javier P Inmaculada A Luis I D | | 0，，18： | 1 |
| 17 | A tutorial on text-independent speaker verification显示文摘 | BIMBOT F BONASTRE J F FREDOUILLLE C GRAVIER G IVAN M C MEIGNIER S MERLIN T JAVIER O G DIJANA P D REYNOLDS D A | 2004 | EURASIP Journal on Applied Signal Processing2004，，4： | 1 |
| 18 | Modular Product Architecture 显示文摘 | Jeffrey B D Javier P Gonzalez Z | 2001 | Design Studies2001，22，5： | 1 |
| 19 | Low cost navigation system for UAV 显示文摘 | Sergio D L P Javier A | 2005 | Aerospace Science and Technology2005，9，： | 1 |
| 20 | Detection of plasmidmediated AmpC β-lactamase genes in clinical isolates by using multiplex PCR显示文摘 | Javier F Perez P Nancy D H | 2002 | J Clin Microbiol2002，40，6： | 1 |
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