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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 | N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis: Randomized,placebo-controlled pilot study显示文摘AIM: To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine (NAC) co-administration with mesalamine in ulcerative colitis (UC) patients. METHODS: Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine (2.4 g/d) plus N-acetyl-L-cysteine (0.8 g/d) (group A) or mesalamine plus placebo (group B). Patients were monitored using the Modified Truelove-Witts Severity Index (MTWSI). The primary endpoint was clinical remission (MTWSI ≤ 2) at 4 wk. Secondary endpoints were clinical response (defined as a reduction from baseline in the MTWSI of ≥ 2 points) and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS: Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine (group A) and mesalamine plus placebo (group B) respectively (OR = 1.71; 95% CI: 0.46 to 6.36; P = 0.19; NNT = 7.7). Analysis of variance (ANOVA) of data indicated a significant reduction of MTWSI in group A (P = 0.046) with respect to basal condition without significant changes in the group B (P = 0.735) during treatment. Clinical responses were 66% (group A) vs 44% (group B) after 4 wk of treatment (OR = 2.5; 95% CI: 0.64 to 9.65; P = 0.11; NNT = 4.5). Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups. CONCLUSION: In group A (oral NAC combined with mesalamine) contrarily to group B (mesalamine alone), the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects. | Luis G Guijarro Jose Mate Javier P Gisbert Jose Luis Perez-Calle Ignacio Marín-Jimenez Encarna Arriaza Tomás Olleros Mario Delgado Maria S Castillejo David Prieto-Merino Venancio Gonzalez Lara Amado Salvador Pea | 2008 | World Journal of Gastroenterology2008，14，18： | 2 |
| 3 | Real-time image processing for crop/weed discrimination in maize fields显示文摘 | Xavier P Burgos-Artizzu Angela Ribeiro Maria Guijarro | | 0，，02： | 1 |
| 4 | Rigidity in nonnegative curvature显示文摘 | Guijarro L Petersen P | 1997 | Ann Scient Ec Norm Sup1997，30，： | 1 |
| 5 | The central role of nuclear factor- κ B in mesangial cell activation显示文摘 | Massy ZM Guijarro C Micheal P | | 0，，： | 1 |
| 6 | Real-time im- age processing for crop/weed discrimination in maize fields 显示文摘 | Xavier P Burgos-Artizzu Angela Ribeiro Maria Guijarro | 2010 | Com- puters and Electronics in Agriculture2010，75，2： | 1 |
| 7 | The effects of time on pH and gas values in the blood contain in the umbilical cord显示文摘 | Valenzuela P Guijarro R | 2006 | Acta Obstet Gynecot Scand2006，85，11： | 1 |
| 8 | Purification and charactrerization of an extracellular protease from the fish pathogen Yersinia ruchei and effect of culture conditions on production显示文摘 | Secades P Guijarro J A | 1999 | Applied and Environmental Microbiology1999，65，9： | 1 |
| 9 | Rigidity in nonnegative curvature 显示文摘 | Guijarro L Petersen P | 1997 | Ann Scient EC Norm Sup1997，30，： | 1 |
| 10 | Mercury retrieval from flue gas by monolithic adsorbents based on sulfurized sepiolite显示文摘 | Mendioroz S Guijarro M I Bermejo P J | 1999 | Environmental Science & Technology1999，33，10： | 1 |
| 11 | Participative site-specific agriculture analysis for smallholders显示文摘 | Pau Arag6 Galindo Granell C Molin P G Guijarro J H | 2012 | Precision Agriculture2012，13，5： | 1 |
| 12 | Preparation and use of aziridino alcohols as promoters for the enantioselective addition of dialkylzinc reagents to N-(diphenylphosphinoyl) imines显示文摘 | ANDERSSON P G GUIJARRO D TANNER D | 1997 | J Org Chem1997，62，21： | 1 |
| 13 | Enantioselective addition of dialkylzinc reagents to N-(diphenylphos-phinoyl) imines promoted by 2-azanorbornylmethanols 显示文摘 | GUIJARRO D PINHO P ANDERSSON P G | 1998 | J Org Chem1998，63，8： | 1 |
| 14 | The effects of time on pH and gas values in the blood contain in the umbilical cord显示文摘 | Valenzuela P Guijarro R | 2006 | Acta Obstet Gynecol Scand2006，85，11： | 1 |
| 15 | Purification and characterization of an extracellular protease from the fish pathogen yersinia ruckeri and effect of culture conditions on production 显示文摘 | Secades P Guijarro J A | 1999 | Appl Environm Microblol1999，65，9： | 1 |
| 16 | Voltammertric Determination of Pentachlorophenol at a Glassy Carbon Electrode显示文摘 | Guijarro E C Yanez-Sedeno P Pingarron Carrazon J M | 1988 | Analyst1988，113，： | 1 |
| 17 | A characterization of inner product spaces based on orthogonal relations related to height's theorem 显示文摘 | ALSINA C GUIJARRO P TOMAS M S | 1995 | Rocky Mountain Journal of Mathematics1995，25，3： | 1 |
| 18 | Purification and characterization of an extracellular protease from the fish pathogen Yersinia ruckeri and effect of culture conditions on production显示文摘 | Secades P Guijarro J A | 1999 | Appl Environ Microbiol1999，65，9： | 1 |
| 19 | The effects of time on p H and gas values in the blood contain in the umbilical cord显示文摘 | Valenzuela P Guijarro R | 2006 | Acta Obstet Gynecol Scand2006，85，11： | 1 |
| 20 | Purification and characterization of an extraeellular protease from the fish pathogen Yersinia ruckeri and effect of culture conditions on production显示文摘 | SECADES P GUIJARRO J A | 1999 | Applied and Environmental Microbiology1999，65，： | 1 |
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