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| 1 | Tyrosine kinase of insulin-like growth factor receptor as target for novel treatment and prevention strategies of colorectal cancer显示文摘AIM: To investigate the antineoplastic potency of the novel insulin-like growth factor 1 receptor (IGF-1R) tyro- sine kinase inhibitor (TKI) NVP-AEW541 in cell lines and primary cell cultures of human colorectal cancer (CRC). METHODS: Cells of primary colorectal carcinomas were from 8 patients. Immunostaining and crystal violet stain- ing were used for analysis of growth factor receptor pro- tein expression and detection of cell number changes, respectively. Cytotoxicity was determined by measuring the release of the cytoplasmic enzyme lactate dehydro- genase (LDH). The proportion of apoptotic cells was determined by quantifying the percentage of sub-G1 (hypodiploid) cells. Cell cycle status reflected by the DNA content of the nuclei was detected by flow cytometry. RESULTS: NVP-AEW541 dose-dependently inhibited the proliferation of colorectal carcinoma cell lines and primary cell cultures by inducing apoptosis and cell cycle arrest. Apoptosis was characterized by caspase-3 activa- tion and nuclear degradation. Cell cycle was arrested at the G1/S checkpoint. The NVP-AEW541-mediated cell cycle-related signaling involved the inactivation of Akt and extracellular signal-regulated kinase (ERK) 1/2, the upregulation of the cyclin-dependent kinase inhibitors p21Waf1/CIP1 and p27Kip1, and the downregulation of the cell cycle promoter cyclin D1. Moreover, BAX was upregu- lated during NVP-AEW541-induced apoptosis, whereas Bcl-2 was downregulated. Measurement of LDH release showed that the antineoplastic effect of NVP-AEW541 was not due to general cytotoxicity of the compound. However, augmented antineoplastic effects were ob-served in combination treatments of NVP-AEW541 with either 5-FU, or the EGFR-antibody cetuximab, or the HMG-CoA-reductase inhibitor fluvastatin. CONCLUSION: IGF-1R-TK inhibition is a promising novel approach for either mono- or combination treatment strategies of colorectal carcinoma and even for CRC che- moprevention. | Michael Hpfner Andreas P Sutter Alexander Huether Viola Baradari Hans Scherübl | 2006 | World Journal of Gastroenterology2006，12，35： | 10 |
| 2 | Signaling pathways involved in the inhibition of epidermal growth factor receptor by erlotinib in hepatocellular cancer显示文摘瞄准:在肝细胞癌(HCC ) 检验导致 erlotinib 的生长抑制的内在的机制。方法:在基因表示的导致 Erlotinib 的改变用 cDNA 数组技术被评估;在蛋白质表示或蛋白质激活的变化用西方的弄污由于象 IGF-1-induced EGFR transactivation 一样的 erlotinib 治疗被调查。结果:Erlotinib 治疗禁止了 mitogen 激活和抄写(STAT ) 的激活的蛋白质(地图)-kinase 小径和信号变换器调停了表明哪个导致了调整由 cDNA 数组技术示威了的基因的 apoptosis 和房间周期的一个改变的表达式。象与象 Bcl-2, Bcl-X (L) 或 jun D 一样的 antiapoptotic 因素的一条下面规定联系的 caspases 和 gadds 一样的 proapoptotic 因素的 Overexpression 说明了让 erlotinib 的力量导致 apoptosis。支持 G1/S-transition 的房间周期管理者并且在 cyclin 依赖的激酶禁止者和 gadds 的表示上的 Downregulation 响应 erlotinib 贡献了 G1/G0-arrest 的正式就职。而且,我们显示了由 IGF-1-receptor 的调停 EGFR 的发信号的 transactivation 并且在受体受体十字谈话显示出 erlotinib 的禁止的效果。结论:我们的学习在 HCC 房间和 thus 使 EGFR-TK-inhibition 的行动的机制的理解清楚些可能便于 additively 或 synergistically 行动的联合治疗的设计。而且,我们对 erlotinib 处理作出回应的小径上的数据能在以后预言肿瘤的应答的海角到 EGFR-TKIs 是有用的。 | Alexander Huether Michael Hpfner Andreas P Sutter Viola Baradari Detlef Schuppan Hans Scherübl | 2006 | World Journal of Gastroenterology2006，12，32： | 7 |
| 3 | Effects of Nerve Growth Factor and Nitric Oxide Synthase Inhibi- tors on Amyloid Precursor Protein mRNA Levels and Protein Stability显示文摘 | Mackinnon J C Huether P Kalisch B E | 2012 | Open Biochem J2012，6，： | 1 |
| 4 | Wavelet preprocessing for high range resolution radar classification 显示文摘 | Huether B M Gustafson S C Broussard R P | 2001 | IEEE Transactions on Aerospace and Electronic Sys- tems2001，37，4： | 1 |
| 5 | Erlotinib induces cell cycle arrest and apoptosis in hepatocellular cancer cells and enhances chemosensitivity towards cytostatics 显示文摘 | Huether A Hopfner M Sutter A P | 2005 | J Hepatol2005，43，4： | 1 |
| 6 | Targeting the epidermal growth factor receptor by gefitinib for treatment of hepatocenular carcinoma 显示文摘 | Hopfner M Sutter A P Huether A | 2004 | J Hepatol2004，41，6： | 1 |
| 7 | Wavelet preprocessing for high range resolution radar classification 显示文摘 | Huether B M Gustafson S C Broussard R P | 2001 | IEEE Transactions on Aerospace and Electronic Systems2001，37，4： | 1 |
| 8 | Efficacy of a cell extract from Actinobacillus(Haemophilus) pleuropneumoniae serotype 1 against disease in swine显示文摘 | Fedorka-Cray P J Huether M J Stine D L | 1990 | Infect Immun1990，58，： | 1 |
| 9 | Efficacy of a cell extract from Actinobacillus pleuropneumoniae serotype 1 against disease in swine 显示文摘 | Fedorka-Cray P J Huether M J Stine D L | 1990 | Infect Immun1990，58，： | 1 |
| 10 | Efficacy of a cell extract from Aetinobaeillus Pleuropneumoniae serotype laganist disease in swine显示文摘 | FEDORKA-CRAY P J HUETHER M J STINE D L | 1991 | Infect Immun1991，58，： | 1 |
| 11 | Wavelet preprocesing for high range resolution radar classification显示文摘 | Huether Brain M Gustafson Steven C Broussard Randy P | 2001 | IEEE Transactions on Aerospace and Electronc Systems2001，37，4： | 1 |
| 12 | Efficary of a cell extract from Actinobacillus pleuropneumoniae serotype laganist disease in swine显示文摘 | Fedorka-cray P J Huether M J Stine D L | 1991 | Infect Immun1991，58，： | 1 |
| 13 | Efficacy of a cell extract from Actinobacillus Plettropmeumoniae serotype against disease in swine Infect显示文摘 | Fedorka-cray P J Huether M J Stine D L | 1991 | Immun1991，58，： | 1 |
| 14 | Erlotinib induces cellcycle arrest and apoptosis in hepatocellular cancer cells and enhances chemosensitivity towards cytostatics 显示文摘 | HUETHER A HPFNER M SUTTER A P | 2005 | J Hepato2005，43，4： | 1 |
| 15 | Wavelet preprocessing for high range resolution radar classification显示文摘 | GUSTAFSON S C BROUSSARD R P | 2001 | IEEE Traus on AES2001，37，4： | 1 |
| 16 | Erlotinib induces cell cycle arrest and apoptosis in hepatocellular cancer cells and enhances chemosensitivity towards cytostatics显示文摘 | Huether A Hopfner M Sutter A P | 2005 | J Hepatol2005，43，4： | 1 |
| 17 | Efficacy of a cell extract from Actinobacillus pleuropmeumoniae serotype laganist disese in swine显示文摘 | Fedorka-cray P J Huether M J Stine D L | 1991 | Infect Immun1991，58，： | 1 |
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