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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 | Regulation of epithelium-specific Ets-like factors ESE-1 and ESE-3 in airway epithelial cells: potential roles in airway inflammation显示文摘航线发炎是许多呼吸障碍的特点,例如气喘和膀胱的纤维变性。在发炎触发的航线基因表示的变化在这些疾病的致病起一个关键作用。基因连接研究建议 ESE-2 和 ESE-3,编码上皮特定的 Ets-domain-containing 抄写因素,是候选人气喘危险性基因。我们这里报导 et 家庭抄写因素 ESE-1 的另一个成员的表示,以及 ESE-3,起来在支气管的上皮的房间线由煽动性的 cytokines interleukin-1beta (IL-1beta ) 和肿瘤坏死 factor-alpha (TNF-alpha ) 调整了。有 IL-1beta 和 TNF-alpha 的这些房间的处理为 ESE-1 和 ESE-3 导致了信使 rna 表示的戏剧的增加。我们证明导致的表示被抄写因素 NF-kappaB 的激活调停。我们描绘了 ESE-1 和 ESE-3 倡导者并且识别了为导致 cytokine 的表达式被要求的 NF-kappaB 有约束力的序列。另外,我们也表明那 ESE-1 在上面调整 ESE-3 表示, down 由 cytokines 调整它的自己的正式就职。最后,我们在 Elf3 显示出那(对人的 ESE-1 相应) 猛烈老鼠,煽动性的 cytokine interleukin-6 (IL-6 ) 的表示是调整的 down。我们的调查结果建议 ESE-1 和 ESE-3 在航线发炎起一个重要作用。 | Jing Wu Rongqi Duan Huibi Cao Deborah Field Catherine M Newnham David R Koehler Noe Zamel Melanie A Pritchard Paul Hertzog Martin Post A Keith Tanswell Jim Hu | 2008 | Cell Research2008，18，6： | 6 |
| 3 | Drainage of single plateau borders: direct observation of rigid and mobile interfaces 显示文摘 | KOEHLER S A HILGENFELDT S WEEKS E R | 2002 | Physical Review E2002，66，04： | 1 |
| 4 | Astrocytes and the Regulation of Cerebral Blood Flow显示文摘 | Koehler RC Roman R J Harder DR | 2009 | Trends Neurosci2009，32，3： | 1 |
| 5 | Complex seismic trace analysis显示文摘 | Taner M T Koehler F Sheriff R E | 1979 | Geophysics1979，44，6： | 1 |
| 6 | Computed tomography in the staging of esophageal carcinoma显示文摘 | PICUS D BALFE D KOEHLER R | 1983 | Radiology1983，146，： | 1 |
| 7 | The relationship between native speaker judgments of nonnative pronunciation and deviance in segmentals, prosody and syllable structure 显示文摘 | Anderson-Hsieh J Johnson R & Koehler K | 1992 | Language Learning1992，42，4： | 1 |
| 8 | Complex seismic trace analysis显示文摘 | Taner M T Koehler F Sheriff R E | 1979 | Geophysics1979，44，6： | 1 |
| 9 | Molecular analysis of cytoplasmic genetic variation in Holstein cows显示文摘 | BROWN D R KOEHLER C M LINDBERG G L | 1989 | J Anim Sci1989，67，8： | 1 |
| 10 | Complex seismic Trace analysis显示文摘 | Taner M T Koehler F Sheriff R E | 1979 | Geophysics1979，44，6： | 1 |
| 11 | Microstructure and dynamics of wormlike micellar solutions formed by mixing cationic and anionic surfactants显示文摘 | KOEHLER R D KALER E W KALER E W | 2000 | J Phys Chem B2000，104，11： | 1 |
| 12 | Small interfering RNA-mediated suppression of dUTPase sensitizes cancer cell lines to thymidylate synthase inhibition显示文摘 | KOEHLER S E LADNER R D | 2004 | Mol Pharmacol2004，66，3： | 1 |
| 13 | Biologically active amines in foods: A review显示文摘 | Rice S L Eitenmiller R R Koehler P E | 1976 | Journal of Milk and Food Technology1976，39，： | 1 |
| 14 | Complex seismic trace analysis 显示文摘 | Taner M T Koehler F Sheriff R E | 1979 | Geophysics1979，44，6： | 1 |
| 15 | Lumbar disc herniation:level increase with age显示文摘 | Dammers R Koehler PJ | 2002 | Surg Neurol2002，58，34： | 1 |
| 16 | Laparoscopy versus laparotomy in endumetrial cancer: first analysis of survival of a randomized prospective study 显示文摘 | Tozzy R Malur S Koehler C | 2005 | Miniminvasive Gynecol2005，12，2： | 1 |
| 17 | Long-term acidification of farmland in northern Idaho and eastern Washington 显示文摘 | Mahler R L Halvorson A R Koehler F E | 1985 | Communications in Soil Science and Plant Analysis1985，16，： | 1 |
| 18 | A new finite element method in micromagnetics显示文摘 | Chen W Fredkin D R Koehler T R | 1993 | IEEE Trans Magn1993，29，： | 1 |
| 19 | Advances in gastrointestinal intervention:the treatment of gastroduodenal and colorectal obstruction with metallic stents显示文摘 | Mauro M A Koehler R E Baron T H | 2000 | Radiology2000，215，3： | 1 |
| 20 | Effects of increased intraabdominal pressure on regional blood flow in newborn lambs显示文摘 | Buckj R Koehler RC | 1983 | Anesthesiology1983，59，： | 1 |
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