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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 | Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells显示文摘AIM: To investigate the antiproliferative effect of the histone deacetylase (HDAC) inhibitor MS-275 on cholangiocarcinoma cells alone and in combination with conventional cytostatic drugs (gemcitabine or doxorubicin) or the novel anticancer agents sorafenib or bortezomib. METHODS: Two human bile duct adenocarcinoma cell lines (EGI-1 and TFK-1) were studied. Crystal violet staining was used for detection of cell number changes. Cytotoxicity was determined by measuring the release of the cytoplasmic enzyme lactate dehydrogenase (LDH). Apoptosis was determined by measuring the enzyme activity of caspase-3. Cell cycle status reflected by the DNA content was detected by flow cytometry.RESULTS: MS-275 treatment potently inhibited the proliferation of EGI-1 and TFK-1 cholangiocarcinoma cells by inducing apoptosis and cell cycle arrest. MS-275-induced apoptosis was characterized by activation of caspase-3, up-regulation of Bax and down-regulation of Bcl-2. Cell cycle was predominantly arrested at the G1/S checkpoint, which was associated with induction of the cyclin-dependent kinase inhibitor p21Waf/CIP1. Furthermore, additive anti-neoplastic effects were observed when MS-275 treatment was combined with gemcitabine or doxorubicin, while combination with the multi-kinase inhibitor sorafenib or the proteasome inhibitor bortezomib resulted in overadditive anti-neoplastic effects.CONCLUSION: The growth of human cholangiocarcinoma cells can be potently inhibited by MS-275 alone or in combination with conventional cytostatic drugs or new, targeted anticancer agents. | Viola Baradari Michael Hpfner Alexander Huether Detlef Schuppan Hans Scherübl | 2007 | World Journal of Gastroenterology2007，13，33： | 10 |
| 3 | 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 |
| 4 | MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer显示文摘 | Nicola Valeri Chiara Braconi Pierluigi Gasparini Claudio Murgia Andrea Lampis Viola Paulus-Hock Jonathan R. Hart Lynn Ueno Sergei I. Grivennikov Francesca Lovat Alessio Paone Luciano Cascione Khlea M. Sumani Angelo Veronese Muller Fabbri Stefania Carasi H | 2014 | Cancer Cell2014，，： | 2 |
| 5 | Multi-modal volume registration by maximization of mutual infcrmation显示文摘 | Wells W M Ⅲ Viola P Atsumi H | 1996 | Med Image Anal1996，3，1： | 1 |
| 6 | Multi-modal Volume Registration by Maximization of Mutual Information显示文摘 | Well W M Viola P Atsumi H | 1996 | Medical Image Analysis1996，1，1： | 1 |
| 7 | Multi-modal volume registration by maximization of mutual information 显示文摘 | WELLS W M VIOLA P ATSUMI H | 1996 | Med Image Anal1996，1，1： | 1 |
| 8 | Persistence of genetically altered fields in head and neck cancer patients:biological and clinical implications显示文摘 | Maarten P Tabor Ruud H Brakenhoff Viola M M van Houten | 2001 | Clinical Cancer Research2001，7，6： | 1 |
| 9 | Phosphorylated cAMP response element-binding protein as a molecular marker of memory processing in rat hippocampus: effect of novelty 显示文摘 | Viola H Furman M lzquierdo LA | 2000 | J Neurosci2000，20，23： | 1 |
| 10 | Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from passiflora coerulea显示文摘 | WOLFMAN C VIOLA H PALADINI A | 1994 | Pharmaeol Biochem1994，47，1： | 1 |
| 11 | 6-Met hyl-apigenin and hesperidin : new valeriana flavonoids wit h activity on the CNS显示文摘 | MARDER M VIOLA H WASOWSKI C | 2003 | Phannacol Biochem Behav2003，75，3： | 1 |
| 12 | Transforaminal lumbar interbody fusion:a safe technique with satisfacto ry three to five year results显示文摘 | Hackenberg L Halm H Viola B | 2005 | Eur Spine J2005，14，6： | 1 |
| 13 | Transforaminal lumbar interbody fusion: a safe technique with satisfactory three to five year resuits显示文摘 | Hackenberg L Henry H Viola B | 2005 | Spine2005，14，： | 1 |
| 14 | Multi-modal volume regis- tration by maximization of mutual information 显示文摘 | Wells W M Viola P Atsumi H | 1996 | Med Image Anal1996，3，1： | 1 |
| 15 | Multi-modal volume registration by maximization of mutual information显示文摘 | Wells III W M Viola P Atsumi H | 1996 | Medical Image Analysis1996，1，1： | 1 |
| 16 | The L- type Ca(2+ ) channel as a therapeutic target in heart disease显示文摘 | Viola HM Macdonald WA Tang H | 2009 | Curr Med Chem2009，16，26： | 1 |
| 17 | Muti-modal volume registration by maximization of mutual information显示文摘 | Wells Ⅲ W M Viola P Atsumi H | 1996 | Medical Image Analysia1996，1，1： | 1 |
| 18 | 6-Methylapigenin and hesperidin:new valeriana flavonoids with activity on the CNS显示文摘 | MARDER M VIOLA H WASOWSKI C | 2003 | Pharmacol Biochem Behav2003，75，3： | 1 |
| 19 | Phosphorylation state of CREB in the rat hippocampus:a molecular switch between spatial novelty and spatial familiarity显示文摘 | Moncada D Viola H | | Neurobiology of Learning and Memory0，，： | 1 |
| 20 | Treatment of ectopic ossification about the elbow显示文摘 | Viola RW Hastings H | 2000 | Clin Orthop Relat Res2000，，370： | 1 |
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