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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 review of rescue regimens after clarithromycin-containing triple therapy failure (for Helicobacter pylori eradication)显示文摘 | Alicia C Marin Adrian G McNicholl Javier P Gisbert | 2013 | Expert Opinion on Pharmacotherapy2013,,7: | 2 |
| 3 | 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 |
| 4 | Development of di- gestive enzymes in common dentex Dentex dentex during early on- togeny 显示文摘 | Gisbert E Gim6nez G Fern6ndez I | 2009 | Aquaculture2009,287,: | 1 |
| 5 | A pilot study of atorvastatin treatment in dyslipemid,non-alcoholic fatty liver patients显示文摘 | Gómez-domínguez E Gisbert JP moreno-monteagudo JA | | 0,,11: | 1 |
| 6 | Development of digestive enzymes in common dentex Dentex dentex during early ontogeny 显示文摘 | GISBERT E GIMINEZ G FERNANDEZ I | 2009 | Aquaculture2009,287,34: | 1 |
| 7 | Percutaneous occlusion of femoral artery pseudoaneurysm by para-aneurysmal saline injection显示文摘 | Gisbert G Joseph L Andrej S | 2003 | Catheter- ization and Cardiovascular Interventions2003,58,4: | 1 |
| 8 | Analysis behaviour of static and dynamic properties of ethylene-pro- pylene-diene-methylene crumb rubber mortar显示文摘 | GISBERT A N BORRELL J M G GARCiA F P | 2014 | Construc- tion and Building Materials2014,50,: | 1 |
| 9 | Development ofdigestive enzymes in common dentex Dentex dentex during earlyontogeny显示文摘 | Gisbert E Gimenez G Fernandez I | 2009 | Aquaculture2009,287,34: | 1 |
| 10 | A pilot study of atorvastatin treatment in dyslipemid,non-alcoholic fatty liver patients显示文摘 | G mez-Dom nguez E Gisbert JP Moreno-Monteagudo JA | 2006 | Alimentary Pharmacology & Therapeutics2006,23,11: | 1 |
| 11 | Genetic and physiological characterization of tomato显示文摘 | Marti E Gisbert C Bishop G J | 2006 | Journal of Experimental Botany2006,57,9: | 1 |
| 12 | Development of digestive enzymes in common dentex Dentex dentex during early ontoenv 显示文摘 | Gisbert E Gim6nez G Femfindez I | 2009 | Aauaculture2009,287,34: | 1 |
| 13 | Morphologi- cal development and allometric growth patterns in hatchery-reared California halibut larvae 显示文摘 | Gisbert E Merino G Muguet J B | 2002 | Journal of Fish Biology2002,61,5: | 1 |
| 14 | Development of digestive enzymes in common dentex Dentex dentex during early ontogeny 显示文摘 | Gisbert E Gim6nez G Fernandez I | 2009 | Aquaculture2009,287,34: | 1 |
| 15 | Development of digestive enzymes in common dentex Dentex dentex during early ontogeny显示文摘 | Gisbert E Gim6nez G Ferndndez I | 2009 | Aquaculture2009,287,34: | 1 |
| 16 | Development of digestive enzymes in common dentex Dentex dentex during early ontogeny显示文摘 | Gisbert E Giménez G Fernández I | | 0,,3: | 1 |
| 17 | Development of digestive enzymes in common dentex Dentex dentex during early ontogeny 显示文摘 | GISBERT E GIMtNEZ G FERN /NDEZ I | 2009 | Aquacul- ture2009,287,34: | 1 |
| 18 | Effect of Ibuprofen on Cyclooxygenase and Nitric Oxide Synthase of Gastric Mucosa: Correlation with Endoscopic Lesions and Adverse Reactions显示文摘 | Sonia Gallego-Sandín Jesús Novalbos Aránzazu Rosado Javier P. Gisbert María-ángeles Gálvez-Múgica Antonio G. García José María Pajares Francisco Abad-Santos | 2004 | Digestive Diseases and Sciences2004,,9: | 1 |
| 19 | Does fecal calprotectin predict relapse in patients with Crohn’s disease and ulcerative colitis?显示文摘 | Valle García-Sánchez Eva Iglesias-Flores Raúl González Javier P. Gisbert José María Gallardo-Valverde ángel González-Galilea Antonio Naranjo-Rodríguez Juan F. de Dios-Vega Jordi Muntané Federico Gómez-Camacho | 2009 | Journal of Crohn’s and Colitis2009,,2: | 1 |
| 20 | Development of a citrus genomewide EST collection and cDNA microarray as resources for genomic studies显示文摘 | FORMENT J GADEA J HUERTA L ABIZANDA L AGUSTI J ALAMAR S ALOS E ANDRES F ARRIBAS R BELTRAN J P BERBEL A BLAZQUEZ M A BRUMOS J CANAS L A CERCOS M COLMENERO-FLORES J M CONESA A ESTABLES B GANDIA M GARCIA-MARTINEZ J L GIMENO J GISBERT A GOMEZ G GONZALEZ-CANDELAS L GRANELL A GUERRI J LAFUENTE M T MADUENO F MARCOS J F MARQUES M C MARTINEZ F MARTINEZ-GODOY M A MIRALLES S MORENO P NAVARRO L PALLAS V PEREZ-AMADOR M A PEREZ-VALLE J PONS C RODRIGO I RODRIGUEZ P L ROYO C SERRANO R SOLER G TADEO F TALON M TEROL J TRENOR M VAELLO L VICENTE O VIDAL C ZACARIAS L CONEJERO V | 2005 | Plant Molecular Biology2005,57,3: | 1 |