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| 1 | TRAIL-induced apoptosis of hepatocellular carcinoma cells is augmented by targeted therapies显示文摘AIM:To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors,in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand(TRAIL),on overcoming TRAIL resistance in hepatocellular carcinoma(HCC)and to study the efficacy of agonistic TRAIL antibodies,as well as the commitment of antiapoptotic BCL-2 proteins, in TRAIL-induced apoptosis. METHODS:Surface expression of TRAIL receptors (TRAIL-R1-4)and expression levels of the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL were analyzed by flow cytometry and Western blotting,respectively. Knock-down of MCL-1 and BCL-xL was performed by transfecting specific small interfering RNAs.HCC cellswere treated with kinase inhibitors and chemotherapeutic drugs.Apoptosis induction and cell viability were analyzed via flow cytometry and 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS:TRAIL-R1 and-R2 were profoundly expressed on the HCC cell lines Huh7 and Hep-G2. However,treatment of Huh7 and Hep-G2 with TRAIL and agonistic antibodies only induced minor apoptosis rates.Apoptosis resistance towards TRAIL could be considerably reduced by adding the chemotherapeutic drugs 5-fluorouracil and doxorubicin as well as the kinase inhibitors LY294002[inhibition of phosphoinositol- 3-kinase(PI3K)],AG1478(epidermal growth factor receptor kinase),PD98059(MEK1),rapamycin(mam- malian target of rapamycin)and the multi-kinase inhibitor Sorafenib.Furthermore,the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL play a major role in TRAIL resistance:knock-down by RNA interference increased TRAIL-induced apoptosis of HCC cells.Additionally, knock-down of MCL-1 and BCL-xL led to a significant sensitization of HCC cells towards inhibition of both c-Jun N-terminal kinase and PI3K.CONCLUSION:Our data identify the blockage of survival kinases,combination with chemotherapeutic drugs and targeting of antiapoptotic BCL-2 proteins as promising ways to overcome TRAIL resistance in HCC. | Bruno Christian Koehler Toni Urbanik Binje Vick Regina Johanna Boger Steffen Heeger Peter R Galle Marcus Schuchmann Henning Schulze-Bergkamen | 2009 | World Journal of Gastroenterology2009，15，47： | 9 |
| 2 | Bcl-x_L and Myeloid cell leukaemia-1 contribute to apoptosis resistance of colorectal cancer cells显示文摘AIM: To explore the role of Bcl-xL and Myeloid cell leukaemia (Mcl)-1 for the apoptosis resistance of colorectal carcinoma (CRC) cells towards current treat-ment modalities. METHODS: Bcl-xL and Mcl-1 mRNA and protein ex-pression were analyzed in CRC cell lines as well as human CRC tissue by Western blot,quantitative PCRand immunohistochemistry. Bcl-xL and Mcl-1 protein expression was knocked down or increased in CRC cell lines by applying specific siRNAs or expression plas-mids,respectively. After modulation of protein expres-sion,CRC cells were treated with chemotherapeutic agents,an antagonistic epidermal growth factor recep-tor (EGFR1) antibody,an EGFR1 tyrosine kinase inhibi-tor,or with the death receptor ligand TRAIL. Apoptosis induction and cell viability were analyzed. RESULTS: Here we show that in human CRC tis-sue and various CRC cell lines both Bcl-xL and Mcl-1 are expressed. Bcl-xL expression was higher in CRC tissue than in surrounding non-malignant tissue,both on protein and mRNA level. Mcl-1 mRNA expression was significantly lower in ma-lignant tissues. However,protein expression was slightly higher. Viability rates of CRC cells were significantly decreased after knock down of Bcl-xL expression,and,to a lower extent,after knock down of Mcl-1 expression. Furthermore,cells with reduced Bcl-xL or Mcl-1 expression was more sensitive towards oxaliplatin-and irinotecan-induced apoptosis,and in the case of Bcl-xL also towards 5-FU-induced apoptosis. On the other hand,upregulation of Bcl-xL by transfec-tion of an expression plasmid decreased chemothera-peutic drug-induced apoptosis. EGF treatment clearly induced Bcl-xL and Mcl-1 expression in CRC cells. Apop-tosis induction upon EGFR1 blockage by cetuximab or PD168393 was increased by inhibiting Mcl-1 and Bcl-xL expression. More strikingly,CD95-and TRAIL-induced apoptosis was increased by Bcl-xL knock down. CONCLUSION: Our data suggest that Bcl-xL and,to a lower extent,Mcl-1,are important anti-apoptotic factors in CRC. Specific downregulation of Bcl-xL is a promising approach to sensitize CRC cells towards chemotherapy and targeted therapy. | Henning Schulze-Bergkamen Roland Ehrenberg Lothar Hickmann Binje Vick Toni Urbanik Christoph C Schimanski Martin R Berger Arno Schad Achim Weber Steffen Heeger Peter R Galle Markus Moehler | 2008 | World Journal of Gastroenterology2008，14，24： | 4 |
| 3 | Transscleral diode laser constact cyclophotocoagulation in the treatment of different glaucoma also as primary surgery 显示文摘 | Kramp K Vick HP Guthoff R | 2002 | Graeefe Arch Clin Exp Ophthalmol2002，240，9： | 1 |
| 4 | 显示文摘 | Vick Roy T B Blanch H W Wilke C R | 1983 | Trends of Biotecnology1983，1，： | 1 |
| 5 | Coupling of stochastic elec- tromagnetic fields to a transmission line in a reverberation chamber显示文摘 | Magdowski M Tkachenko S V Vick R | 2011 | IEEE Transactions on Electromagnetic Compatibility2011，53，2： | 1 |
| 6 | Taking educational games se- riously: Using the RETAIN model to design endogenous fantasy into standalone educational games 显示文摘 | Gunter G A Kenny R F Vick E H | 2008 | Educational Technology Re- search and Development2008，56，56： | 1 |
| 7 | Electrocardiographic gating and monitoring in NMR imaging 显示文摘 | Wentdt R E Rokey R Vick G W | 1988 | Magnetic Resonance Imaging1988，4，： | 1 |
| 8 | Time-resolved contrast-enhanced magnetic resonance angiography in pediatric patients using sensitivity encoding显示文摘 | Muthupillai R Vick GW 3rd Flamm SD | 2003 | J Magn Reson Imaging2003，17，： | 1 |
| 9 | Transscleral diode laser contact cyclophotocoagulation in the treatment of different glaucoma,also as primary surgery显示文摘 | Kramp K Vick HP Guthoff R | 2002 | Graefe Arch Clin Exp Ophthalmol2002，240，9： | 1 |
| 10 | Correlative circadian rhythms of cholecystokinin and dopamine content in nuc-leus accumbens and striatum of rat brain显示文摘 | Schade R Vick K Sohr R | 1993 | Behav Brain Res1993，59，： | 1 |
| 11 | Engineering and char- acterization of the long-acting glucagon-like peptide-1 analogue- LY2189165,an Fc fusion protein显示文摘 | Glaesner W Vick AM Millican R | 2010 | Diabetes Metab Res Rev2010，26，4： | 1 |
| 12 | Prospective association of polycystic ovary syndrome withcoronary artery calcification and carotid- intima- media thick-ness :the Coronary Artery Risk Development in Young AdultsWomen’s study 显示文摘 | CALDERON- MARGALIT R SISCO VICK D MERKIN S S etal | 2014 | Arterioscler Thromb Vase Biol2014，34，12： | 1 |
| 13 | Engineering and characterization of the long-acting glucagon-like peptide-1 analogue LY2189265, an Fc fusion protein显示文摘 | GLAESNER W MARK VICK A MILLICAN R | 2010 | Diabetes Res Rev2010，26，4： | 1 |
| 14 | Natural history of muhiple meningiomas显示文摘 | Wong R H Wong A K Vick N | 2013 | Surg Neurol Int2013，4，： | 1 |
| 15 | Choice of intravenous antibi otic prophylaxis for colorectal surgery does matter显示文摘 | Deierhoi R J Dawes L G Vick C | 2013 | J Am Coll Surg2013，217，5： | 1 |
| 16 | 显示文摘 | Vick Roy T B Blanch H W Wilke C R | 1983 | Trends of Biotechnology1983，1，： | 1 |
| 17 | Transscleral diode laser contact cyclophotocoagulation in the treatment of different glaucoma, also as primary surgery显示文摘 | Kramp K Vick HP Guthoff R | 2002 | Graefes Arch Clin Exp Ophthalmol2002，240，9： | 1 |
| 18 | Experimental investiga- tion of solar powered diaphragm and helical pumps 显示文摘 | Vick Brian D Clark R Nolan | 2011 | Solar Energy2011，85，5： | 1 |
| 19 | Transscleral diode laser contactcyclophotocoagulation in the treatment of different glaucomas,also asprimary surgery显示文摘 | Kramp K Vick HP Guthoff R | 2002 | Graefe's Arch Clin Exp Ophthalmol2002，240，9： | 1 |
| 20 | Production of porous carbon thin films by pulsed laser deposition显示文摘 | D Vick Y.Y Tsui M.J Brett R Fedosejevs | 1999 | Thin Solid Films1999，，1： | 1 |
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