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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 | Toll‐Like Receptors and Cytokines are Upregulated during H elicobacter pylori Infection in Children显示文摘 | Hugo Lagunes‐Servin Javier Torres Carmen Maldonado‐Bernal Martha Pérez‐Rodríguez Sara Huerta‐Yépez Armando Madrazo de la Garza Leopoldo Mu?oz‐Pérez Lourdes Flores‐Luna Guillermo Ramón‐García Margarita Camorlinga‐Ponce | 2013 | Helicobacter2013，，6： | 2 |
| 3 | Nested PCR improves detection of infectious hematopoietic necrosis virus in cells coinfected with infectious pancreatic necrosis virus显示文摘 | Marta Alonso Sylvia Rodr??guez Sara I Pérez Prieto | 1999 | Journal of Virological Methods1999，，1： | 2 |
| 4 | IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality显示文摘 | Zhang Hong Neuh?fer Patrick Song Liang Rabe Bj?rn Lesina Marina Kurkowski Magdalena U Treiber Matthias Wartmann Thomas Regnér Sara Thorlacius Henrik Saur Dieter Weirich Gregor Yoshimura Akihiko Halangk Walter Mizgerd Joseph P Schmid Roland | 2013 | Journal of Clinical Investigation2013，，3： | 2 |
| 5 | Firm size and the gains from acquisitions显示文摘 | Sara B Moeller Frederik P Schlingemann René M Stulz | 2004 | Journal of Financial Economics2004，，2： | 1 |
| 6 | Wealth Destruction on a Massive Scale? A Study of Acquiring - Firm Returns in the Recent Merger Wave 显示文摘 | Sara B Moeller Frederik P Schlingemann Ren6 M Stulz | 2005 | Journal of Finance2005，60，2： | 1 |
| 7 | Rho GTPases have diverse effects on the organization of the actin filament system显示文摘 | Aspenstrom P Fransson A Saras J | 2004 | Biochem J2004，377，： | 1 |
| 8 | Oxidation of direct dyes with hydrogen peroxide using ferrous ion as catalyst显示文摘 | P K Malik S K Sara | 2003 | Separation and Purification Technology2003，31，3： | 1 |
| 9 | Evidence for a biphasic apoptotic pathway induced by melatonin in MCF-7 breast cancer cells显示文摘 | Alessandra C Sara P Fabrizio D A | 2009 | J Pineal Res2009，46，3： | 1 |
| 10 | 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 |
| 11 | Bilateral sudden sensorineural hearing loss:review显示文摘 | SARA S A TEH B M FRIEDLAND P | 2014 | J Laryngol Otol2014，128，： | 1 |
| 12 | Image texture analysis of sonograms in chronic inflammations of thyroid gland显示文摘 | Smutek D Sara R Sucharda P | 2003 | Ultra-sound in Medicine and Biology2003，29，13： | 1 |
| 13 | RNA (E6/E7) assays versus- DNA (E6/E7) assays for risk evaluation for women infected with humanpapillomavirus显示文摘 | Cattani P Alessia S Sara D | 2009 | Clin Microbiol2009，47，7： | 1 |
| 14 | EphB signaling directs peripheral nerve regeneration through sox 2 -dependent Schwann cell sorting显示文摘 | Simona P Ilaria N Sara R | 2010 | Cell2010，143，1： | 1 |
| 15 | Osteoarthritis : an o- verview of the disease and its treatment strategies 显示文摘 | Sara - Puttini P Cimmino MA Searpa R | 2005 | Semin Arthri- tis Rheum2005，35，1： | 1 |
| 16 | Firm size and the gains from acquisitions 显示文摘 | Frederik P Schlingemann Rene M Stulz | 2004 | Journal of Financial Economics2004，，73： | 1 |
| 17 | 显示文摘 | Francesca P Sara M Luigi T | 2008 | Water Research2008，156，： | 1 |
| 18 | Spiekerkoetter medium - chain triglycerides impair metabolism and induce hepatic steatosis in very long -chain acyl - CoA dehydrogenase ( VLCAD) - deficient mice 显示文摘 | Sara T Sonja P Frank TV | 2010 | Mole Gen Metab2010，101，1： | 1 |
| 19 | A headspace solid-phase microextraction gas-chromatographic mass-spectrometric method to quantify hexanal in butter during storage as marker of lipid oxidation显示文摘 | SARA P SILVIA S LUCA M C | 2011 | Food Chemistry2011，127，2： | 1 |
| 20 | Brugada Phenocopy in a Patient with Pectus Excavatum: Systematic Review of the ECG Manifestations Associated with Pectus Excavatum显示文摘 | Sara F.M. Awad Raimundo Barbosa‐Barros Lucia de Sousa Belem Camila Pinto Cavalcante Andrés Ricardo Pérez Riera Javier Garcia‐Niebla Daniel D. Anselm Adrian Baranchuk | 2013 | Annals of Noninvasive Electrocardiology2013，，5： | 1 |
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