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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 | Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials显示文摘 | Carsten Bokemeyer Eric Van Cutsem Philippe Rougier Fortunato Ciardiello Steffen Heeger Michael Schlichting Ilhan Celik Claus-Henning K?hne | 2012 | European Journal of Cancer2012，，10： | 5 |
| 3 | 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 |
| 4 | Phase I study of matuzumab in combination with 5-fluorouracil, leucovorin and cisplatin (PLF) in patients with advanced gastric and esophagogastric adenocarcinomas显示文摘 | Tanja Trarbach Marta Przyborek Norbert Schleucher Steffen Heeger Christian Lüpfert Udo Vanhoefer | 2013 | Investigational New Drugs2013，，3： | 3 |
| 5 | Large open-circuit voltage polymer solar cells by poly(3-hexylthiophene) with multi-adducts fullerenes显示文摘Polymer solar cells (PSCs) made by poly(3-hexylthiophene) (P3HT) with multi-adducts fullerenes, [6,6]-phenyl-C61-butyric acid methyl ester (PC61BM), PC61BM-bisadduct (bisPC61BM) and PC61BM-trisadduct (trisPC61BM), were reported. Electrochemistry studies indicated that PC61BM, bisPC61BM and trisPC61BM had step-up distributional lowest unoccupied molecular orbital (LUMO) energy. PSCs made by P3HT with above PC61BMs show a trend of enlarged open-circuit voltages, which is in good agreement with the energy difference between the LUMO of PC61BMs and the HOMO of P3HT. On the contrary, reduced short-circuit currents (Jsc) were observed. The investigation of photo responsibility, dynamics analysis based on photo-induced absorption of composite films, P3HT:PC61BMs and n-channel thin film field-effect transistors of PC61BMs suggested that the short polaron lifetimes and low carrier mobilities were response for reduced Jsc. All these results demonstrated that it was important to develop an electron acceptor which has both high carrier mobility, and good compatibility with the electron donor conjugated polymer for approaching high performance PSCs. | HEEGER Alan J. | 2012 | Science China Chemistry2012，55，5： | 3 |
| 6 | Leakage tests of the stainless steel vessels of the antineutrino detectors in the Daya Bay reactor neutrino experiment显示文摘The antineutrino detectors for the Daya Bay reactor neutrino experiment are liquid scintillator detectors designed to detect electron anti-neutrino via inverse beta interactions with high efficiency and low backgrounds.Since the antineutrino detector will be installed and immerged in water Cherenkov detector and will run for 3 to 5 years,water tightness is critical to the successful operation of the antineutrino detectors.A special seal technique was used for this purpose.Three leak checking methods have been employed to ensure the seal quality.This paper describes the sealing method and leakage testing results. | CHEN XiaoHui LUO XiaoLan HENG YueKun WANG LingShu TANG Xiao MA XiaoYan ZHUANG HongLin BAND Henry R. CHERWINKA Jeff J. XIAO Qiang HEEGER Karsten M. | 2013 | Science China(Technological Sciences)2013，56，1： | 2 |
| 7 | Efficient blue polymer light-emitting diodes from a series of soluble poly (paraphenylene)s显示文摘 | Yang Y Pei Q Heeger A J | 1996 | J Appl Phys1996，79，： | 2 |
| 8 | Photoinduced Electron Tranfser from a Conductiong polymer to Buckminsterfullerene 显示文摘 | Sariciftci N S Smilowitz L Heeger A J | 1992 | Sci- ence1992，398，： | 1 |
| 9 | Soli- tons in polyacetylene显示文摘 | SU Wupei SCHRIEFFER J R HEEGER A J | 1979 | Phys Rev Lett1979，42，25： | 1 |
| 10 | Well-defined donor-acceptor rod-coil diblock copolymers based on P3HT containing C60:The morphology and role as a surfactant in bulkheterojunction solar cells显示文摘 | Yang C Lee J K Heeger A | | 0，，： | 1 |
| 11 | Novel aspects of complement inkidney injury显示文摘 | Vieyra MB Heeger PS | 2010 | Kidney Int2010，77，6： | 1 |
| 12 | Spectroscopic studies of soluble poly(3-alkylthienylenes)显示文摘 | Hotta S Rughooputh S D D V Heeger A J | 1987 | Macromolecules1987，20，： | 1 |
| 13 | Bulk heterojunction solar cell s:morphology and performance relationships显示文摘 | Ye H Kramer E J Heeger A J | 2014 | Chemical Reviews2014，114，14： | 1 |
| 14 | Label-free electronic detec- tion of thrombin in blood senim by using an aptamer-based sensor 显示文摘 | Xiao Y Lubin AA Heeger AJ | 2005 | Angew Chem2005，44，34： | 1 |
| 15 | 25th anniversary article:bulk heterojunction solar cells:understanding the mechanism of operation显示文摘 | HEEGER A J | 2014 | Adv Mater2014，26，1： | 1 |
| 16 | Preparation of PCR-quality mouse genomic DNA with hot sodium hydroxide and tris (HotSHOT)显示文摘 | Truett GE Heeger P Mynatt RL | 2000 | Biotechniques2000，29，1： | 1 |
| 17 | Energytransfer in mixtures of water-soluble oligomers:effectof charge,aggregation,and surfactant complexation显示文摘 | Stork M Gaylord B S Heeger A J | 2002 | Advanced Materials2002，14，5： | 1 |
| 18 | Semiconducting Polymer Diodes: Large Size, Low cost photodetectors with excellent Visible - ultraviolet Sensi- tivity显示文摘 | Yu G Pakbaz K Heeger A J | 1994 | Appl Phys Let1994，64，25： | 1 |
| 19 | SoIi- ton exci-tations in polyacetylene 显示文摘 | SU Wupei SCHRIEFFER J R HEEGER A 1 | 1980 | Phys Rev B1980，22，4： | 1 |
| 20 | Neural encoding of binoc- ular disparity: energy models, position shifts and phase shifts 显示文摘 | FLEET D J WAGNER H HEEGER D J | 1996 | Vision Research1996，36，12： | 1 |
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