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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 | Heparanase: a new metastasis-associated antigen recognized in breast cancer patients by spontaneously induced memory T lymphocytes显示文摘 | Sommerfeldt N Beckhove P Ge Y Sehutz F Choi C Bucur M Domsehke C Sohn C Sehneeweis A Rom J Poll- mann D Leneht D Vlodavsky I Sehirrmaeher V | 2006 | Cancer Res2006，66，15： | 1 |
| 3 | An approach to the arsenic status in cardiovaseular tissues of patients with coronary heart disease 显示文摘 | ROM N D PIZARRO I RIVERA L | 2011 | Hum Exp Toxieol2011，30，9： | 1 |
| 4 | Crucial role of interleukin-1 beta and nitric oxide synthase in silica-induced inflammation and apoptosis in mice显示文摘 | SRIVASTAVA K D ROM W N JAGIRDAR J | 2002 | Am J Respir Crit Care Med2002，165，4： | 1 |
| 5 | Antecedents and consequences of adaptive selling confidence and behavior:a dyadic analysis of salespeople and their customers显示文摘 | Román S Jacobucci D | | 0，，： | 1 |
| 6 | Identification of an autoantibody panel to separate lung cancer from smokers and nonsmokers显示文摘 | Rom W N Goldberg J D Addrizzo - Harris D | 2010 | BMC Cancer2010，10，： | 1 |
| 7 | Evaluation of the relationship between polymorphisms in CYP2C19 and the pharmacokinetics of omeprazole,pantoprazole and rabeprazole显示文摘 | Román M Ochoa D Sánchez-Rojas SD | 2014 | Pharmacogenomics2014，15，15： | 1 |
| 8 | Boundary extraction through gradient-based evolutionary algorithm显示文摘 | ROMáN K CLAUDIO D | 2003 | JCS&T2003，3，1： | 1 |
| 9 | Estimating theparameters of a Gompertz-type diffusion process by means ofSimulated Annealing显示文摘 | Román-Román P Romero D Rubio M A | | 0，，09： | 1 |
| 10 | Crucial role of interleukin-lbeta and nitric oxide synthase in silica-induced inflammation and apoptosis in mice 显示文摘 | SRIVASTAVA K D ROM W N JAGIRDAR J | 2002 | Am J Respir Crit Care Med2002，165，4： | 1 |
| 11 | 查看详情显示文摘 | Román D A Carretero A S Blanco C C Gutiérrez A F | | 0，，07： | 1 |
| 12 | Crucial role of interleukin-1 beta and nitric oxide synthase in silica-induced inflammation and apoptosis in mice显示文摘 | SRIVASTAVA K D ROM W N JAGIRDAR J | 2002 | Am J Respir Crit Care Med2002，165，4： | 1 |
| 13 | Appropriate management of common bile duct stones: A RAND Corporation/UCLA Appropriateness Method statistical analysis显示文摘 | Pablo Parra-Membrives Daniel Díaz-Gómez Román Vilegas-Portero Máximo Molina-Linde Lourdes Gómez-Bujedo Juan Ramón Lacalle-Remigio | 2010 | Surgical Endoscopy2010，，5： | 1 |
| 14 | Crucial role of interleukin-lbeta and nitric oxide synthase in silica-induced inflammation and apoptosis in mice显示文摘 | SRIVASTAVA K D ROM W N JAQIRDAR J | 2002 | Am J Respir Crit Care Med2002，165，4： | 1 |
| 15 | Medición de la legitimidad organizativa: El caso de las Sociedades de Garantía Recíproca显示文摘 | Francisco Díez Martín Alicia Blanco González Camilo Prado Román | 2010 | Cuadernos de Economía y Dirección de la Empresa2010，，43： | 1 |
| 16 | Discovery of gargantulides B and C,new 52-membered macrolactones from Amycolatopsis sp.Complete absolute stereochemistry of the gargantulide family显示文摘Gargantulides B and C,two new and highly complex 52-membered glycosylated macrolactones,were isolated from Amycolatopsis sp.strain CA-230715 during an antibacterial screening campaign.The structures of these giant macrolides were elucidated by 2D NMR spectroscopy and shown to be related to gargantulide A,although containing additional β-glucopyranose and/orα-arabinofuranose monosaccharides separately attached to their backbones.Genome sequencing allowed the identification of a strikingly large 216 kbp biosynthetic gene cluster,among the largest type Ⅰ PKS clusters described so far,and the proposal of a previously unreported biosynthetic pathway for gargantulides A-C.The absolute configurations of gargantulides B and C were assigned based on a combination of NMR and bioinformatics analysis of ketoreductase and enoylreductase domains within the multimodular type Ⅰ PKS.In addition,the absolute stereochemistry of gargantulide A has now been revised and completed.Gargantulides B and C display potent antibacterial activity against a set of drug-resistant Gram-positive bacteria and moderate activity against the clinically relevant Gram-negative pathogen Acinetobacter baumannii. | Daniel Carretero-Molina Francisco Javier Ortiz-López Tetiana Gren Daniel Oves-Costales Jesús Martín Fernando Román-Hurtado Tue Sparholt Jorgensen Mercedes de la Cruz Caridad Díaz Francisca Vicente Kai Blin Fernando Reyes Tilmann Weber Olga Genilloud | 2022 | Organic Chemistry Frontiers2022，9，2： | 0 |
| 17 | Repsol石油公司园区显示文摘 | Jesús Román Concha Pe a Marcus Lassan Carolina Fernández Conchi Cobo Guillermo Vidal Bodo Schumacher Laura Díaz Hubert Lionnez María Millán Hugo Berenguer Guillermo Cervantes Beatriz Heras Zaloa Mayor María Martínez Miguel García Irene Zurdo María Iglesias Alfonso Quiroga 刘亦师 | 2014 | 建筑学报2014，，4： | 0 |
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