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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 | Comparative effects of captopril and L-carnitine on blood pressure and antioxidant enzyme gene expression in the heart of spontaneously hypertensive rats 显示文摘 | Migue C M Monserrat A M | 2010 | European J Pharm aeol2010，632，： | 1 |
| 3 | A new approach for the real-time simulation of tissue deformations in surgery simulation显示文摘 | Monserrat C Meier U Alcaniz M | 2001 | Comput Methods Programs Biomed2001，64，2： | 1 |
| 4 | Validation and comparison of advanced differential interferometry techniques: murcia metropolitan area case study显示文摘 | HERRERA G TOMAS R LOPEZ-SANCHEZ J M DELGADO J VICENTE F MULAS J COOKSLEY G SANCHEZ M DURO J ARNAUD A BLANCO P DUQUE S MALLORQUI J J DE la VEGA-PANIZO R MONSERRAT O | 2008 | ISPRS Journal of Photogrammetry and Remote Sensing2008，，： | 1 |
| 5 | Microcystin-induced oxidative stress in Laeonereis acuta (Polychaeta,Nereididae)显示文摘 | Leo J C Geracitano L A Monserrat J M | 2008 | Marine Environmental Research2008，66，： | 1 |
| 6 | S-implications and R-implications on a finite chain显示文摘 | MAS M MONSERRAT M TORRENS J | 2004 | Kybernetika2004，40，： | 1 |
| 7 | Toxicological effect of hepatotoxins (microcystin) on aquatic organisms显示文摘 | Monserrat J M Pinho G L L Yunes J S | 2003 | Comments on Toxicology2003，9，： | 1 |
| 8 | QL-implications on a finite chain显示文摘 | MAS M MONSERRAT M TORRENS J | 2003 | Proc Eusflat-2003，2003，： | 1 |
| 9 | Comparative effects of captopril and L-carnitine on blood pressure and antioxidant enzyme gene expression in the heart of spontaneously hypertensive rats显示文摘 | MIGUEL-CARRASCO J L MARíA T Monserrat A M | 2010 | European Journal of Pharmacology2010，632，： | 1 |
| 10 | Mutational screening of phospholamban gene in hypertrophic and idiopathic dilated cardiomyopathy and functional study of the PLN -42 C>G mutation 显示文摘 | Medin M Hermida-Prieto M Monserrat L | 2007 | Eur J Heart Fail2007，9，1： | 1 |
| 11 | Deformation Measurement Using Terrestrial Laser Scanning Data and Least Squares 3D Surface Matching显示文摘 | MONSERRAT O CROSETTO M | 2008 | ISPRS Journal of Photogrammetry and Remote Sensing2008，63，1： | 1 |
| 12 | Physiologi- cal and Antioxidant Enzyme Responses to Acute and Chronic Ex- posure of Laeonereis acuta (Polychaeta Nereidiae) to Copper显示文摘 | GERACITANO L MONSERRAT J M BIANCH1NI A | 2002 | Journal of Experimental Marine Biology and Ecology2002，277，2： | 1 |
| 13 | Pollution biomarkers in estuarine animals: Critical review and new perspectives显示文摘 | Monserrat J M Martinez P E Geracitano L A | 2007 | Comp Biochem Physiol C Toxicol Pharmacol2007，146，12： | 1 |
| 14 | Deformation Measurement Using Terrestrial Laser Scanning Data and Least Squares 3D Surface Matching显示文摘 | MONSERRAT O CROSETTO M | 2008 | ISPRS Journal of Photogrammetry & Remote Sensing2008，63，1： | 1 |
| 15 | Physiological and antioxidant enzyme responses to acute and chronic exposure of Laeonereis acuta (Polychaeta, Nereididae) to copper 显示文摘 | GERACITANO L MONSERRAT J M BIANCHINI A | 2002 | Journal of Experimental Marine Biology and Ecology2002，277，2： | 1 |
| 16 | Microcystin-induced oxidativestress in Laeonereis aeuta (Polychaeta, Nereididae)显示文摘 | Leo J C C-eracitano L A Monserrat J M | 2008 | Marine Environmental Re- search2008，66，： | 1 |
| 17 | Fa- milial dilated cardiomyopathy and isolated left ventricular non- compaction associated with lamin A/C gene mutations 显示文摘 | Hermida-Prieto M Monserrat L Castro-Beiras A | 2004 | Am J Cardiol2004，94，1： | 1 |
| 18 | Substrate-free determination of the radical scavenging activity of phenolic compounds by photochemical generation of hydroxyl radicals and HPLC-UV detection显示文摘 | De Carvalho L M Monserrat J M Scholz F | 2013 | Separation Science And Technology2013，48，7： | 1 |
| 19 | Non-sustained ventricular tachycardia in hypertrophic cardiomyopathy显示文摘 | Lorenzo Monserrat Perry M Elliott Juan R Gimeno Sanjay Sharma Manuel Penas-Lado William J McKenna | 2003 | Journal of the American College of Cardiology2003，，5： | 1 |
| 20 | Two types of implications derived from uninorms 显示文摘 | Mas M Monserrat M Torrens J | 2007 | Fuzzy Sets and Systems2007，158，23： | 1 |
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