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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 | An investigation ofbuffer sizing techniques in critical chain scheduling显示文摘 | Tukel O I Rom W O Eksioglu S D | 2006 | European journal of operational research2006，172，2： | 1 |
| 3 | 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 |
| 4 | Power system static-state estimation:Part I,II&III显示文摘 | Schweppe F C Wildes J Rom D B | 1970 | IEEE Transactions on Power Apparatus and Systems1970，89，1： | 1 |
| 5 | The influence of summer pruning current season shoots on growth, floral bud development and winter injury of mature peach trees显示文摘 | ROM C M FERREE D C | 1984 | HortSci1984，19，： | 1 |
| 6 | An investigation of buffer sizing techniques in critical chain scheduling显示文摘 | Tukel O I Rom W O Eksioglu S D | 2006 | European Journal of Operational Research2006，172，： | 1 |
| 7 | An investigation ofbuffer sizing techniques in critical chain scheduling显示文摘 | TUKEL O I ROM W O EKSIOGLU S D | 2006 | European JournalofOperational Research2006，172，2： | 1 |
| 8 | Power system static-state estimation, part Ⅰ~Ⅲ显示文摘 | Schweppe F C Wildes J Rom D B | 1970 | IEEE Transactions on Power Apparatus and Systems1970，89，1： | 1 |
| 9 | Power system stat- ic state estimation, parts 1, 2, 3显示文摘 | Schweppe F C Wildes J Rom D B | 1970 | IEEE Transactions on Power Apparatus and Systems1970，89，1： | 1 |
| 10 | Power system static-state estimation, part Ⅰ~Ⅲ显示文摘 | Schweppe F C Wildes J Rom D B | 1970 | IEEE Transactions on Power Apparatus and Systems1970，89，1： | 1 |
| 11 | An investigation of buffer sizing techniques in critical chain scheduling显示文摘 | TUKEL O I ROM W O EKSIOGLU S D | 2006 | European J of Operational Research2006，172，2： | 1 |
| 12 | From biomarkers to population responses in Nereis diversicolor:Assessment of stress in estuarine ecosystems显示文摘 | DUROU C SMITH B D ROMO M | 2007 | Ecotoxicology and Environmental Safety2007，66，： | 1 |
| 13 | 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 |
| 14 | Ben- eficial effects of docosahexaenoic acid on cognition in age - related cognitive decline 显示文摘 | YURKO - MAURO K MCCARTHY D ROM D | 2010 | Alzheimers Dement2010，6，6： | 1 |
| 15 | 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 |
| 16 | An investigation of buffer sizing techniques in critical chain scheduling显示文摘 | Oya I Tukel Walter O Rom Sandra D Eksioglu | | 0，，02： | 1 |
| 17 | Power system static state estimation part Ⅰ,Ⅱ and Ⅲ显示文摘 | Schweppe F C Wildes J Rom D B | | 0，，01： | 1 |
| 18 | 显示文摘 | Cazorla-Amorós D Linares-Solano A | 1995 | Carbon1995，33，： | 1 |
| 19 | Power System Static-State Estimation: Part I1II 显示文摘 | SCHWEPPE F C WILDES J’ROM D B | 1970 | IEEE Transactions on PAS1970，89，1： | 1 |
| 20 | An inves- tigation of buffer sizing techniques in critical chain scheduling 显示文摘 | TUKEL O I ROM W O EKSIOGLU S D | 2006 | European Journal of Operational Re- search2006，172，2： | 1 |
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