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| 1 | Growth factor receptors and related signalling pathways as targets for novel treatment strategies of hepatocellular cancer显示文摘Growth factors and their corresponding receptors are commonly overexpressed and/or dysregulated in many cancers including hepatocellular cancer (HCC). Clinical trials indicate that growth factor receptors and their related signalling pathways play important roles in HCC cancer etiology and progression, thus providing rational targets for innovative cancer therapies. A number of strategies including monoclonal antibodies, tyrosine kinase inhibitors ('small molecule inhibitors') and antisense oligonucleotides have already been evaluated for their potency to inhibit the activity and downstream signalling cascades of these receptors in HCC. First clinical trials have also shown that multi-kinase inhibition is an effective novel treatment strategy in HCC. In this respect sorafenib, an inhibitor of Raf-, VEGF- and PDGF-signalling, is the first multi-kinase inhibitor that has been approved by the FDA for the treatment of advanced HCC. Moreover, the serine-threonine kinase of mammalian target of rapamycin (mTOR) upon which the signalling of several growth factor receptors converge plays a central role in cancer cell proliferation. mTOR inhibition of HCC is currently also being studied in preclinical trials. As HCCs represent hypervascularized neoplasms, inhibition of tumour vessel formation via interfering with the VEGF/VEGFR system is another promising approach in HCC treatment. This review will summarize the current status of the various growth factor receptor-based treatment strategies and in view of the multitude of novel targeted approaches, the rationale for combination therapies for advanced HCC treatment will also be taken into account. | Michael Hpfner Detlef Schuppan Hans Scherübl | 2008 | World Journal of Gastroenterology2008，14，1： | 33 |
| 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 | Liver cirrhosis显示文摘 | Detlef Schuppan Nezam H Afdhal | 2008 | The Lancet . 2008 (9615)2008，，： | 4 |
| 5 | Treatment of gastrointestinal neuroendocrine tumors with inhibitors of growth factor receptors and their signaling pathways: Recent advances and future perspectives显示文摘The limited efficacy of conventional cytotoxic treatment regimes for advanced gastrointestinal neuroendocrine cancers emphasizes the need for novel and more effective medical treatment options. Recent findings on the specific biological features of this family of neoplasms has led to the development of new targeted therapies, which take into account the high vascularization and abundant expression of specific growth factors and cognate tyrosine kinase receptors. This review will briefly summarize the status and future perspectives of antiangiogenic, mTOR- or growth factor receptor-based pharmacological approaches for the innovative treatment of gastrointestinal neuroendocrine tumors. In view of the multitude of novel targeted approaches, the rationale for innovative combination therapies, i.e. combining growth factor (receptor)-targeting agents with chemo- or biotherapeutics or with other novel anticancer drugs such as HDAC or proteasome inhibitors will be taken into account. | Michael Hpfner Detlef Schuppan Hans Scherübl | 2008 | World Journal of Gastroenterology2008，14，16： | 4 |
| 6 | Liver cirrhosis显示文摘 | Detlef Schuppan Nezam H Afdhal | 2008 | The Lancet2008，，9615： | 4 |
| 7 | Targeted medical therapy of biliary tract cancer:Recent advances and future perspectives显示文摘The limited efficacy of cytotoxic therapy for advanced biliary tract and gallbladder cancers emphasizes the need for novel and more effective medical treatment options. A better understanding of the specific biological features of these neoplasms led to the development of new targeted therapies, which take the abundant expression of several growth factors and cognate tyrosine kinase receptors into account. This review will briefly summarize the status and future perspectives of antiangiogenic and growth factor receptor-based pharmacological approaches for the treatment of biliary tract and gallbladder cancers. In view of multiple novel targeted approaches, the rationale for innovative therapies, such as combinations of growth factor (receptor)-targeting agents with cytotoxic drugs or with other novel anticancer drugs will be highlighted. | Michael Hpfner Detlef Schuppan Hans Scherübl | 2008 | World Journal of Gastroenterology2008，14，46： | 3 |
| 8 | Enucleation and Limited Pancreatic Resection Provide Long-Term Cure for Insulinoma in Multiple Endocrine Neoplasia Type 1显示文摘 | Bartsch Detlef K Albers Max Knoop Richard Kann Peter H Fendrich Volker Waldmann Jens | 2014 | Neuroendocrinology2014，，4： | 2 |
| 9 | Sample analysis using laser ablation inductively coupled plasma mass spectrometry显示文摘 | Detlef G Bodo H | 2005 | TrAC Trends in Analytical Chemistry2005，24，3： | 1 |
| 10 | Climate policy through changing consumption choices:Options and obstacles for reducing greenhouse gas emissions显示文摘 | Girod B Detlef P V Edgar G H | 2014 | Global Environmental Change2014，25，4： | 1 |
| 11 | Damage mechanisms of cast Al-Si-Mg alloys under superimposed thermal-mechanical fatigue and high-cycle fatigue loading显示文摘 | TILMANN B DETLEF L JOCHEN L INGO H | 2007 | Materials Science and Engineering A2007，468，： | 1 |
| 12 | Liver cirrhosis显示文摘 | Detlef Schuppan Nezam H Afdhal | 2008 | The Lancet2008，，9615： | 1 |
| 13 | 查看详情显示文摘 | Hanan H M Detlef W B | | 0，，： | 1 |
| 14 | Automated gene ontology annotation for anonymous sequence data显示文摘 | Steffen H Detlef G Hans L | 2003 | Nucleic Acids Research2003，31，13： | 1 |
| 15 | Automated gene ontology annotation for anonymous sequence data显示文摘 | STEFFEN H DETLEF G HANS L | 2003 | Nucleic Acids Research2003，31，13： | 1 |
| 16 | Effect of Nitrite, NO and N2O on Methanogensis and Other Redox Processes in Anoxic Rice Field Soil 显示文摘 | Detlef Klue ber H Conrad R | 1998 | Ferns Mocrobiology1998，25，： | 1 |
| 17 | Schmallenberg virus—Two years of experiences显示文摘 | Kerstin Wernike Franz Conraths Gina Zanella Harald Granzow Kristel Gache Horst Schirrmeier Stephen Valas Christoph Staubach Philippe Marianneau Franziska Kraatz Detlef H?reth-B?ntgen Ilona Reimann Stéphan Zientara Martin Beer | 2014 | Preventive Veterinary Medicine2014，，： | 1 |
| 18 | Blockade of IGF-1 receptor tyrosine kinase has antineoplastic effects in hepatocellular carcinoma cells显示文摘 | Michael H?pfner Alexander Huether Andreas P. Sutter Viola Baradari Detlef Schuppan Hans Scherübl | 2006 | Biochemical Pharmacology2006，，10： | 1 |
| 19 | Ab initio studies of rhodium(I) - N- alkenyiamide complexes with cis- and trans-coordinating phosphines: relevance for the mechanian of catalytic asmmetric Hydrogemtion of prochiral delaydromino acids显示文摘 | ACHIM K ARMIN B DETLEF H | 1997 | Organometallics1997，16，10： | 1 |
| 20 | Blockade of IGF-1 receptor tyrosine kinase has antineoplastic effects in hepatocellular carcinoma cells显示文摘 | Michael H?pfner Alexander Huether Andreas P. Sutter Viola Baradari Detlef Schuppan Hans Scherübl | 2006 | Biochemical Pharmacology2006，，10： | 1 |
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