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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 | 原因不明的脑卒中患者心房纤维化增加:心脏磁共振成像研究显示文摘一些被归类为原因不明的缺血性脑卒中患者可能有左心房和左心耳结构或功能的改变,增加了他们的血栓栓塞风险。该研究使用心脏磁共振成像比较不同病因的缺血性脑卒中患者的左心房和左心耳结构及功能。研究人员前瞻性连续纳入缺血性脑卒中患者样本。 | 刘莉 叶鹏 Fonseca AC Alves P Inácio N Marto JP Viana-Baptista M Pinho-E-Melo T Ferro JM Almeida AG | 2018 | 中华高血压杂志2018，26，3： | 2 |
| 3 | , manipulation of insulin-like growth factor binding protein-3 levels显示文摘 | CHEUNG C W TAYLOR P J KIRKPATRICK C M et aL Therapeutic value of orally administered silibinin in renal cell carcinoma | 2007 | Br J Urol Inter2007，100，2： | 1 |
| 4 | a quantitative analysis显示文摘 | LASLETT G M GREEN P F DUDDY I R et' al Thermal annealing of fission tracks in apatite 2 | 1987 | Chemical Geology1987，65，1： | 1 |
| 5 | Low-density geochemical mapping in Portugal显示文摘 | Ferreira M M In?cio P Morgado M J | 2001 | Applied Geochemistry2001，16，： | 1 |
| 6 | Management of adult idiopathic thrombocytopenic purpura显示文摘 | NAKHOUL IN KOZUCH P VARMA M | 2006 | Clin Adv2006，4，： | 1 |
| 7 | Radionuclide transport and k fracture and crushed rock col- 显示文摘 | P KANEN M et retardation in roc umn experiments Hydrology 1997 SIITARIKAUPPI M HA- al | 1997 | Journal of Contaminant1997，26，14： | 1 |
| 8 | Cognitive progression in epilepsy 显示文摘 | Seidenberg M Da Bruce H | 2007 | Neuropsyehol Rev2007，17，4： | 1 |
| 9 | Wide Optical Band Gap Window Layers for Solar Cells显示文摘 | Zhenrui Yu Ines Pereyra Carreno M N P | 2001 | Solar Energy Materials & Solar Cells2001，66，： | 1 |
| 10 | Spatial pattern and ecological analysis显示文摘 | LEGENDRE P FORT IN M J | 1989 | Vegetatio1989，80，： | 1 |
| 11 | Evidence of a cultured strain of the marine rhathymum from Malaysia 显示文摘 | Cailaud A de la Iglesia P okadaic acid production in dinoflagellate Prorocentrum Campers M | 2010 | Toxieon2010，55，： | 1 |
| 12 | 显示文摘 | Rahman M McVetty P B E,Li G Y,Development of SRAP1SNP and multiplexed SCAR molecular markers for the major seed coat color gene in Brassica rapa L | 2007 | Theoretical and Applied Genetics2007，115，8： | 1 |
| 13 | Effects of the Inclu2sion of Yeast Culture (Saccharomyces Plus Growth Modium) in the Diet of Dairy Cows on Milk Yield and Forage Degradation and Fermentation Patterns in the Rumen of Steers显示文摘 | Williams P E V Tait C A Ines G M | 1991 | J Anim Sci1991，69，： | 1 |
| 14 | Significant tests and analysis of covariance structures 显示文摘 | Bentler P M Bonett D goodness of fit in the G | 1980 | Psychological Bulletin1980，，88： | 1 |
| 15 | Simulation of the Madden-Julian Oscillation in a coupled general circulation model Part I: Comparisons with observations and an atmosphere-only GCM显示文摘 | INNESS P M SLINGO J M | 2003 | J Climate2003，16，3： | 1 |
| 16 | Management of adult idiopathic thrombocytopenic purpura 显示文摘 | Nakhoul IN Kozuch P Varma M | 2006 | Clin Adv Hematol Oncol2006，4，14： | 1 |
| 17 | Effects of social anxiety on non verbal accuracy and response time: facial expression 显示文摘 | Mu 11 ins D T Duke M P | 2004 | Journal of Nonverbal Behavior2004，28，1： | 1 |
| 18 | Path planning for a mobile robot显示文摘 | ALEXO POULOS C GR IFF IN P M | 1992 | IEEE Transactions on Systems Man and Cybernetics1992，22，2： | 1 |
| 19 | Evidence that also in non proliferating cells the number of NORs is a marker of protein synthesis activity 显示文摘 | Jozsa L Kannus P Jarvinen M Atrophy and regeneration of rat calf muscles cause reversible changes in the number of nucleolar organizer regions | 1993 | Lab Invest1993，69，2： | 1 |
| 20 | Plasma funetionalization of poly(vinyl alcohol) hydrogel for cell adhesion enhancement 显示文摘 | IN() J M CHEVALLIER P LETOURNEUR D | 2013 | Biomatter2013，3，25： | 1 |
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