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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 | Chronic Renal Allograft Rejection:Immunologic and Nonimmunologic Risk Factors显示文摘 | Massy Z A Guijarro C Wiederkehr M R | 1996 | Kidney Int1996，49，： | 1 |
| 3 | Amyloid fibril formation by an SH3 domain显示文摘 | Guijarro J I Sunde M Jones J A | 1998 | Proe Natl Aead Sei U S A1998，95，： | 1 |
| 4 | Amyloid fibril formation by an SH3 domain 显示文摘 | Guijarro J I Sunde M Jones J A | 1998 | Proe Natl Acad Sci USA1998，95，： | 1 |
| 5 | Automatic expert system based on images for accuracy crop row detection in maize fields显示文摘 | Guerrero J M Guijarro M Montalvo M | 2013 | Expert Systems with Applications2013，40，29： | 1 |
| 6 | Ruthenium-catal- ysed asymmetric transfer hydrogenation of N-(tert-hu- tanesulfinyl) imines显示文摘 | GUIJARRO D PABLO O YUS M | 2009 | Tetrahedron Lett2009，50，38： | 1 |
| 7 | Li- popolysaccharide activates Toll - like receptor 4 ( TLR4 ) - media- ted NF - KB signaling pathway and proinflammatory response in hu- man pericytes显示文摘 | Guijarro - Muftoz I Compte M Alvarez - Cienfuegos A | 2014 | J Biol Chem2014，289，4： | 1 |
| 8 | Generation of allylic and benzylic organolithium reagents from the corresponding ester, amide, carbonate, carbamate and urea derivatives显示文摘 | M Alonso D Guijarro M Yus | 1999 | Tetrahedron1999，55，11： | 1 |
| 9 | Neuropeptide Y has a stimulatory action on feeding behavior in goldfish (Carassius auratus) 显示文摘 | LOPEZ-PATINO M A GUIJARRO A I ISORNA E | 1999 | European Journal of Pharmaceutical Sciences1999，3，77： | 1 |
| 10 | Cellular senescence induced by p53-ras cooperation is independent of p21waf1 in murine embryo fibroblasts显示文摘 | Castro ME del Valle Guijarro M | 2004 | J Cell Biochem2004，92，3： | 1 |
| 11 | Clinical-therapeutic management of thoracoscopy in pleural effusion:a groundbreaking technique in the twenty-first century显示文摘 | Galbis JM Mata M Guijarro R | | 0，，01： | 1 |
| 12 | 3 - hydroxy- 3 -methylglutaryl coenzyme A reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture显示文摘 | Guijarro C Blanco - Colio LM Ortego M | 1998 | Circ Res1998，83，5： | 1 |
| 13 | 3-hydroxy-3-methy lglutarylcoenzyme a reductase and isoprenylation inhibitors induce apoptosis of vascuclar smooth muscle cells in culture 显示文摘 | Guijarro C Blanco-Colio L M Drtego M | 1998 | Circ Res1998，83，5： | 1 |
| 14 | Real- time image processing for crop/weed discrimination in maize fields 显示文摘 | Burgos-Artizzu XP Ribeiro A Guijarro M | 2011 | Computers and Electronics in Agriculture2011，75，2： | 1 |
| 15 | Neuropeptide Y has a stimulatory action on feeding behavior in goldfish (Carassius auratus) 显示文摘 | LOPEZ-PATINO M A GUIJARRO A L ISORNA E | 1999 | Pharmacol1999，3，77： | 1 |
| 16 | NPY receptors and opioidergic system are in-volved in NPY-induced feeding in goldfish显示文摘 | DE PEDRO N LOPEZ-PATINO M A GUIJARRO AI | 2000 | Pep-tides2000，21，10： | 1 |
| 17 | Family risk factors associated with adolescent pregnancy:Study of a group of adolescent girls and their family in Ecuador显示文摘 | Guijarro S Naranjo J Padilla M Gutierez R Lammers C Blum R.W | | 0，，： | 1 |
| 18 | Automatic segmentation of relevant textures in agricultural images 显示文摘 | Guijarro M Pajaresb G Riomorosc I | 2011 | Computer and electronics in agriculture2011，75，1： | 1 |
| 19 | 3-hydroxy-3-methylglutaryl coenzyme A reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture显示文摘 | Blanco-Colio LM Ortego M Alonso C Ortiz A Plaza JJ | 1998 | Circ Res1998，83，5： | 1 |
| 20 | Neuropeptide Y has a stimulatory action on feeding behavior in goldfish (Carassius auratus)显示文摘 | L6pez-Patifio M A Guijarro A I Isoma E | 1999 | European journal of pharmacology1999，377，23： | 1 |
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