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| 1 | Proteasome inhibition-induces endoplasmic reticulum dysfunction and cell death of human cholangiocarcinoma cells显示文摘AIM: To determine if proteasome inhibition induces apoptosis in human cholangiocarcinoma cells, and if so, to elucidate the cellular mechanisms. METHODS: Studies were performed in the human KMCH, KMBC, and Mz-ChA-1 cholangiocarcinoma, and normal rat cell lines. MG132, a peptide aldehyde, which inhibits the chymotrypsin-like activity of the proteaosome was employed for this study. Apoptosis was assessed morphologically by 4'-6-Diamidino-2-phenylindole (DAPI) nuclear staining and fluorescence microscopy. Mitochondrial membrane potential was examined using a fluorescent unquenching assay. Ultrastructural changes during cell death were examined using transmission electron microscopy (TEM). Caspase 3/7 activity was assessed using an enzymatic-based fluorescent assay. Cytosolic-free calcium concentrations were measured using Fura-2 and digitized fluorescent microscopy. RESULTS: MG132, a proteasome inhibitor, induced apoptosis in all the cholangiocarcinoma cell lines examined. In contrast, minimal cytotoxicity was observed in normal rat cholangiocytes. Apoptosis was time-and -concentration-dependent. There was no change in the mitochondrial membrane potential between treated and untreated cells. Ultrastructural examination by transmission electron microscopy displayed the classic features of apoptosis, but in addition, there was also dramatic vacuolization of the endoplasmic reticulum (ER). Unexpectedly, no increase in caspase 3/7 activity was observed in MG132 treated cells, nor did the pancaspase inhibitor, Q-VD-OPh prevent cell death. The protein synthesis inhibitor, cycloheximide, blocked apoptosis induced by proteosome inhibitor indicating that ER dysfunction was dependent upon the formation of new proteins. CONCLUSION: Proteosome inhibition induces ERdysfunction and caspase-independent cell death selectively in human cholangiocarcinoma cells. Proteasome inhibitors warrant evaluation as anticancer agents for the treatment of human cholangiocarcinoma. | Yucel Ustundag Steven F Bronk Gregory J Gores | 2007 | World Journal of Gastroenterology2007，13，6： | 9 |
| 2 | Constitutive androstane receptor agonist, TCPOBOP,attenuates steatohepatitis in the methionine choline-deficientdiet-fed mouse显示文摘AIM:To ascertain whether constitutive androstane receptor(CAR)activation by 1,4-bis-2-(3,5,-dichloropyridyloxy)benzene(TCPOBOP)modulates steatohepatitis in the methionine choline-deficient(MCD)diet-fed animal.METHODS:C57/BL6 wild-type mice were fed the MCD or standard diet for 2 wk and were treated with either the CAR agonist,TCPOBOP,or the CAR inverse agonist,androstanol.RESULTS:Expression of CYP2B10 and CYP3A11,known CAR target genes,increased 30-fold and 45-fold,respectively,in TCPOBOP-treated mice fed the MCD diet.TCPOBOP treatment reduced hepatic steatosis(44.6 ± 5.4% vs 30.4 ± 4.5%,P < 0.05)and serum triglyceride levels(48 ± 8 vs 20 ± 1 mg/dL,P < 0.05)in MCD diet-fed mice as compared with the standard diet-fed mice.This reduction in hepatic steatosis was accompanied by an increase in enzymes involved in fatty acid microsomal ω-oxidation and peroxisomal β-oxidation,namely CYP4A10,LPBE,and 3-ketoacyl-CoA thiolase.The reduction in steatosis was also accompanied by a reduction in liver cell apoptosis and inflammation.In contrast,androstanol was without effect on any of the above parameters.CONCLUSION:CAR activation stimulates induction of genes involved in fatty acid oxidation,and ameliorates hepatic steatosis,apoptosis and inflammation. | Edwina S Baskin-Bey Akira Anan Hajime Isomoto Steven F Bronk Gregory J Gores | 2007 | World Journal of Gastroenterology2007，13，42： | 3 |
| 3 | Tolerance of nonsteroidal antiinflammatory drugs in patients with inflammatory bowel disease显示文摘 | Gregory F Bonner Michelle Walczak Laurel Kitchen Manuel Bayona | 2000 | The American Journal of Gastroenterology2000，，8： | 2 |
| 4 | Standardized measurement of the future liver remnant prior to extended liver resection: Methodology and clinical associations显示文摘 | Jean-Nicolas Vauthey Amin Chaoui Kim-Anh Do Malcolm M Bilimoria Marc J Fenstermacher Chuslip Charnsangavej Marshall Hicks Guido Alsfasser Gregory Lauwers Irvin F Hawkins James Caridi | 2000 | Surgery2000，，5： | 2 |
| 5 | Advances in the Treatment and Outcome of Brainstem Cavernous Malformation Surgery: A Single-Center Case Series of 300 Surgically Treated Patients显示文摘 | Adib A Abla Gregory P Lekovic Jay D Turner Jean G de Oliveira Randall Porter Robert F Spetzler | 2011 | Neurosurgery2011，，2： | 2 |
| 6 | Formation velocity and density-The diagnostic basis for stratigraphic traps 显示文摘 | Gardner G H F Gardner L W Gregory A R | 1974 | Geophysics1974，39，6： | 1 |
| 7 | No Significant Association of 14 Candidate Genes With Schizophrenia in a Large European Ancestry Sample: Implications for Psychiatric Genetics显示文摘 | Sanders Alan R Duan Jubao Levinson Douglas F Shi Jianxin He Deli Hou Cuiping Burrell Gregory J Rice John P Nertney Deborah A Olincy Ann Rozic Pablo Vinogradov Sophia Buccola Nancy G Mowry Bryan J Freedman Robert Amin Farooq Black Donald W | 2008 | The American Journal of Psychiatry2008，，4： | 1 |
| 8 | Sympathetic skin response and cardiovascular autonomic function tests in Par- kinson's disease and multiple system atrophy with autonomic failure 显示文摘 | DE MARINIS M STOCCHI F GREGORI B | 2000 | Mov Disord2000，15，6： | 1 |
| 9 | Plastic-damage model for cyclic loading of concrete structures 显示文摘 | Lee J Gregory L F | 1998 | Journal of Engineer- ingMechanics1998，124，4： | 1 |
| 10 | Management of uterine leimyosarcoma in Australia显示文摘 | Gregory B Gard F | 1999 | Aust NZ J Obstet Gynaecol1999，39，1： | 1 |
| 11 | Laser-induced shock compression of monocrystalline copper: characterization and analysis 显示文摘 | MEYERS M A GREGORI F KAD B K | 2003 | Acta Materialia2003，51，5： | 1 |
| 12 | The effect of diameter ratio and volume ratio on the viscosity of bimodal suspensions of polymer latices 显示文摘 | GREENWOOD R LUCKHAM P F GREGORY T | 1997 | Journal of Colloid and Interface Science1997，191，1： | 1 |
| 13 | Anterior and posterior fusion for children with tuberculosis of the spine显示文摘 | Altman Gregory T Altnab Daniel T Frankovitch Karl F | 1996 | Clin Orthop Relat Res1996，，325： | 1 |
| 14 | Behavior- al genetic analyses of prosocial behavior in adolescents 显示文摘 | Gregory AM Light-H:iusermann JH Rijsdijk F | 2009 | Dev Sci2009，12，1： | 1 |
| 15 | Trends and patterns of vaginal birth after cesarean availability in the united states显示文摘 | Kimberly D Gregory Moshe F | | 0，，04： | 1 |
| 16 | Im-mune evasion genes from filarial nematodes显示文摘 | Maizels R M Gomez E N* Gregory W F | 2001 | Int JParasitol2001，31，9： | 1 |
| 17 | Formation velocity and density: the diagnostic basics for stratigraphic traps 显示文摘 | Gardner G H F Gardner L W Gregory A R | 1974 | Geophysics1974，39，： | 1 |
| 18 | Minimising the viscosity of concentrated dispersions by using bimodal particle size distributions 显示文摘 | GREENWOOD R LUCKHAM P F GREGORY T | 1998 | Colloids and Surfaces A : Physicochemical and Engineering Aspects1998，144，13： | 1 |
| 19 | A Bayesian method for the introduction of probabilistic networks from data显示文摘 | Gregory F Copper Edward Herskovits | 1992 | Machine Learning1992，9，： | 1 |
| 20 | Formation velocity and density-the diagnostic basis for stratigraphic traps 显示文摘 | Gardner G H F Gardner L W Gregory A R | 1974 | Geophysics1974，39，6： | 1 |
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