|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 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 | Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases显示文摘瞄准:为了如果特定的细胞毒素的 T 房间回答能与恶意的肝在病人被导致,估计,肿瘤与无线电频率对待脱离(RFA ) 。方法:有颜色的肝转移的六个病人表面的癌症并且 6 与肝细胞,癌(HCC ) 经历了 RFA。血以前被取样,在 RFA 以后的 4 和 8 wk。测试抗原是活体检视从每个病人获得的自体同源的肝和肿瘤溶解产物。外部 T 房间激活被一个干扰素鲸鱼群妈(IFNgamma ) 估计分泌物试金和流动血细胞计数。T 房间是双 stained 让 CD4/CD8 和 IFNgamma 检测细胞毒素的 T 房间。积极的 IFNgamma 和 IFNgamma 否定 T 房间的比率作为刺激索引(SI ) 被决定。估计细胞溶解的活动, T 房间与人的 CaCo 颜色被共同孵化 cytosolic adenylate 激酶的表面的癌症和 HepG2 HCC 房间和版本被酶试金测量。结果:在 RFA SI 前是 0.021 (+/- 0.006 ) 为 CD4 (+) 并且 0.022 (+/- 0.004 ) 为对非恶意的肝织物的 CD8 (+) T 房间并且 0.018 (+/- 0.005 ) 为 CD4 (+) 并且 0.021 (+/- 0.004 ) 为对自体同源的肿瘤织物的 CD8 (+) 房间。在对肿瘤织物的 RFA SI 以后的四个星期增加了到 0.109 (+/- 0.005 )为 CD4 (+)并且 0.11 (+/- 0.012 )为对 HCC 的 CD8 (+) T 房间,并且到 0.115 (+/- 0.031 )为 CD4 (+)并且 0.15 (+/- 0.02 )为为颜色的 CD8 (+)房间表面的转移( P <
0.0001 )。没有增加的 SI 被观察与非,恶性瘤织物根本预定点。与 2.62 在对各自的癌症房间的 RFA 细胞溶解的的活动前是低的(+/- 0.37 ) 相对的光单位(RLU ) ,而是超过 100 合拢的玫瑰在 RFA 以后的 4 和 8 wk。自发的版本是 2% 最大值在所有实验释放的 <
。结论:病人与主要并且肝的继发性瘤在 RFA 以后与 CD8 (+) T 房间的一项戏剧性地增加的肿瘤 specific 细胞溶解的活动显示出重要肿瘤特定的细胞毒素的 T 房间刺激。 | Johannes Hansler Thaddaus Till Wissniowski Detlef Schuppan Astrid Witte Thomas Bernatik Eckhart Georg Hahn Deike Strobel | 2006 | World Journal of Gastroenterology2006，12，23： | 22 |
| 3 | 大鼠结缔组织生长因子部分cDNA序列的克隆及其mRNA在实验性肝纤维化中的表达显示文摘目的克隆出大鼠结缔组织生长因子(connective tissue growth factor, CTGF)的部分cDNA序列,并观察在实验性肝纤维化大鼠肝脏中 CTGF mRNA的表达改变。方法根据小鼠CTGF mRNA序列设计引物,用 RT-PCR从大鼠肝脏总 RNA中扩增出一段 430 bp的产物,并测定其序列。将 16只雌性 Wistar大鼠随机分为胆管堵塞组(n=8)及假手术组(n=8)。6周后取大鼠肝脏提取总RNA,利用多探针以核酸酶保护分析法测定CTGF及TGFβ_1的mRNA水平。结果克隆出的大鼠CTGF cDNA序列在核酸水平与小鼠的同源性为95%。胆汁性肝硬化大鼠肝脏中 TGF β_1及 CTGF的 IRNA水平分别为假手术组大鼠的 4倍和 7倍。结论在实验性肝纤维化大鼠肝脏中CTGF mRNA的表达水平明显上调。 | 贾继东 Michael Bauer Gabriele Boigk Martin Ruelh Detlef Schuppan 王宝恩 | 2000 | 中华肝脏病杂志2000，8，2： | 22 |
| 4 | Role of the receptor for advanced glycation end products in hepatic fibrosis显示文摘AIM:To study the role of advanced glycation end products(AGE)and their specifi c receptor(RAGE)in the pathogenesis of liver fi brogenesis.METHODS:In vitro RAGE expression and extracellular matrix-related gene expression in both rat and human hepatic stellate cells(HSC)were measured after stimulation with the two RAGE ligands,advanced glycation end product-bovine serum albumin(AGE-BSA)and Nε-(carboxymethyl)lysine(CML)-BSA,or with tumor necrosis factor-α(TNF-α).In vivo RAGE expression was examined in models of hepatic fi brosis induced by bile duct ligation or thioacetamide.The effects of AGE-BSA and CML-BSA on HSC proliferation,signal transduction and profi brogenic gene expression were studied in vitro.RESULTS:In hepatic fibrosis,RAGE expression was enhanced in activated HSC,and also in endothelial cells,inflammatory cells and activated bile duct epithelia.HSC expressed RAGE which was upregulated after stimulation with AGE-BSA,CML-BSA,and TNF-α.RAGE stimulation with AGE-BSA and CML-BSA did not alter HSC proliferation,apoptosis,fibrogenic signal transduction and fibrosis-or fibrolysis-related gene expression,except for marginal upregulation of procollagen α1(Ⅰ)mRNA by AGE-BSA.CONCLUSION:Despite upregulation of RAGE in activated HSC,RAGE stimulation by AGE does not alter their fibrogenic activation.Therefore,RAGE does not contribute directly to hepatic fibrogenesis. | Christina Lohwasser Daniel Neureiter Yury Popov Michael Bauer Detlef Schuppan | 2009 | World Journal of Gastroenterology2009，15，46： | 13 |
| 5 | 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 |
| 6 | Helicobacter pylori upregulates prion protein expression in gastric mucosa: A possible link to prion disease显示文摘AIM: Pathological prion protein (PrPSC) is responsible for the development of transmissible spongiform encephalopathies (TSE). While PrPc enters the organism via the oral route, less data is available to know about its uptake and the role of gastrointestinal inflammation on the expression of prion precursor PrPc, which is constitutively expressed in the gastric mucosa.METHODS: We studied PrPc expression in the gastric mucosa of 10 Helicobacter pylori-positive patients before and after successful H pylori eradication compared to non-infected controls using RT-PCR and Western blotting.The effect of central mediators of gastric inflammation,i.e., gastrin, prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) on PrPc expression was analyzed in gastric cell lines.RESULTS: PrPc expression was increased in H pyloriinfection compared with non-infected controls and decreased to normal after successful eradication. Gastrin,PGE2, and IL-1β dose-dependently upregulated PrPc in gastric cells, while TNF-α had no effect.CONCLUSION: H pylori infection leads to the upregulation of gastric PrPc expression. This can be linked to H pylori induced hypergastrinemia and increased mucosal PGE2 and IL-1β synthesis.H pylori creates a milieu for enhanced propagation of prions in the gastrointestinal tract. | Peter C Konturek Karolina Bazela Vitally Kukharskyy Michael Bauer Eckhart G Hahn Detlef Schuppan | 2005 | World Journal of Gastroenterology2005，11，48： | 9 |
| 7 | 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 |
| 8 | 教育现实情境取向的教育心理学研究--德国近十年教育心理学发展的基本走向显示文摘迄今国内对德国教育心理学的发展状况了解、评介甚少。在全球化的今天,将目光聚焦于曾对心理学,其中包括教育心理学做出过巨大贡献,至今仍在国际心理学界占一席之地的德国十分必要。文章以三种德文教育心理学权威学术期刊近十年发表的论文为资料源进行分析,概括出德国教育心理学的新近发展特点是:以教育现实情境为基本研究取向,以学习者心理研究为中心,以量化研究为主并注重多方法结合,凸现了教育心理学对教育实践的指导价值。德国教育心理学发展的基本走向为:重视校外环境对学习者的影响,重视教与学双主体的相关能力及面临的问题的解决,重视以多媒体网络技术为基础的新媒体的作用、重视整合研究及国际交流等。 | 冯小俐 张大均 Detlef H.Rost | 2012 | 心理科学2012，35，2： | 6 |
| 9 | Liver-specific therapies for metastases of neuroendocrine pancreatic tumors显示文摘The presence or development of liver metastases in patients with neuroendocrine pancreatic tumors is the most important prognostic factor.Liver resection,transplantation and many different therapeutic approaches are discussed in this special review. | Volker Fendrich Patrick Michl Nils Habbe Detlef Klaus Bartsch | 2010 | World Journal of Hepatology2010，2，10： | 6 |
| 10 | Evolving therapies for liver fibrosis显示文摘 | Schuppan Detlef Kim Yong Ook | 2013 | Journal of Clinical Investigation2013，，5： | 5 |
| 11 | HASTY modulates miRNA biogenesis by linking pri-miRNA transcription and processing显示文摘Post-transcriptional gene silencing mediated by microRNAs(miRNAs)modulates numerous developmental and stress response pathways.For the last two decades,HASTY(HST),the ortholog of human EXPORTIN 5,was considered to be a candidate protein that exports plant miRNAs from the nucleus to the cytoplasm.Here,we report that HST functions in the miRNA pathway independent of its cargo-exporting activity in Arabidopsis.We found that Arabidopsis mutants with impaired HST shuttling exhibit normal subcellular distribution of miRNAs.Interestingly,protein-protein interaction and microscopy assays showed that HST directly interacts with the microprocessor core component DCL1 through its N-terminal domain.Moreover,mass spectrometry analysis revealed that HST also interacts independently of its N-terminal domain with the mediator complex subunit MED37.Further experiments revealed that HST could act as a scaffold to facilitate the recruitment of DCL1 to genomic MIRNA loci by stabilizing the DCL1-MED37 complex,which in turn promotes the transcription and proper processing of primary miRNA transcripts(primiRNAs).Taken together,these results suggest that HST is likely associated with the formation of the miRNA biogenesis complex at MIRNA genes,promoting the transcription and processing of primiRNAs rather than the direct export of processed miRNAs from the nucleus. | Damian A.Cambiagno Axel J.Giudicatti Agustin L.Arce Delfina Gagliardi Lei Li Wei Yuan Derek S.Lundberg Detlef Weigel Pablo A.Manavella | 2021 | Molecular Plant2021，14，3： | 5 |
| 12 | 如何提高单胃动物对微量元素的吸收率显示文摘微量元素在动物体内履行着重要的生理功能,如在新陈代谢中发挥着复杂的功能,并且它们的缺乏可导致动物机体生理功能的紊乱,这就是为什么它们需要通过饲料向动物提供的原因。虽然微量元素在保持家畜最佳的健康状况和生产性能上具有重要的作用,然而添加微量元素所产生益处的重要性往往被人们低估。 | 陈建康 Detlef Kampf | 2014 | 国外畜牧学(猪与禽)2014，34，3： | 4 |
| 13 | Organosolv Lignin for Non-Isocyanate Based Polyurethanes (NIPU) as Wood Adhesive显示文摘A non-isocyanate-based polyurethane(NIPU)wood adhesive was produced from organosolv lignin,which is a bio-sourced raw material,available in large quantities and produced as a by-product of the paper industry.The formulation of this new lignin-based NIPU adhesive,which is presented,was chemically characterised by Matrix-Assisted Laser Desorption Ionization Time of Flight(MALDI ToF)mass spectrometry and by Fourier Transform Infra-Red(FTIR)spectrometry analyses.The oligomers formed were determined and showed that the three species involved in the NIPU adhesive preparation were formed by the co-reaction of the three reagents used:lignin,dimethyl carbonate,and hexamethylene diamine.Linear and branched structures were both identi-fied.Mechanical properties of the adhesive were determined using the Automated Bonding Evaluation System(ABES)and internal bond(IB)strength test of the laboratory particleboard bonded with it.The adhesive has shown satisfactory mechanical properties after hot pressing at 230℃.Such a temperature is used industrially in the most modern particleboard factories,but since it is hardly feasible for more conventional wood bonding equipment,the reactivity of the NIPU adhesive was successfully increased with the addition of a small percentage of a silane coupling agent.With the addition of the silane,the proposed NIPU adhesive could also be used at a hot-pressing temperature lower than 200℃. | Jaša Saražin Antonio Pizzi Siham Amirou Detlef Schmiedl MilanŠernek | 2021 | Journal of Renewable Materials2021，9，5： | 4 |
| 14 | Liver cirrhosis显示文摘 | Detlef Schuppan Nezam H Afdhal | 2008 | The Lancet . 2008 (9615)2008，，： | 4 |
| 15 | 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 |
| 16 | Liver cirrhosis显示文摘 | Detlef Schuppan Nezam H Afdhal | 2008 | The Lancet2008，，9615： | 4 |
| 17 | ⅩⅧ型胶原mRNA在实验性肝纤维化大鼠肝脏中的表达显示文摘目的了解XⅧ型胶原(collagenXⅧ,CXⅧ)mRNA在实验性肝纤维化中的定量改变。方法以逆行胆管硬化注射加结扎的方法制备大鼠胆管堵塞性肝纤维化模型,以假手术组大鼠为对照组。提取肝脏总RNA,以核酸酶保护分析(RNA酶保护分析)定量测定前胶原α1(XⅧ)mRNA水平,并与α1(Ⅰ)和金属蛋白酶组织抑制因子1(TIMP-1)的mRNA变化相比较。结果与假手术组大鼠相比,胆管堵塞性肝纤维化大鼠肝脏前胶原α1(Ⅰ)及TIMP-1mRNA水平分别升高20倍及4倍;而肝纤维化大鼠肝脏前胶原α1(XⅧ)mRNA水平仅升高到1.8倍。结论肝纤维化时肝脏XⅧ胶原仅轻度升高.这种变化类型可能和XⅧ胶原主要由肝实质细胞表达有关。 | 贾继东 Michael Bauer Garbriele Boigk Martin Ruehl Detlef Schuppan 王宝恩 | 2000 | 中华肝脏病杂志2000，8，5： | 4 |
| 18 | PPCPs - A human and veterinary fingerprint in the Pearl River delta and northern south China sea显示文摘This study aimed to identify stable indicator contaminants of pharmaceuticals and personal care products(PPCPs)to trace the anthropogenic fingerprint of the Pearl River plume in the coastal waters of the northern South China Sea.40 PPCPs were under investigation,of which 14 were detected along the Pearl River Estuary and 4 on the shelf of the northern South China Sea.Results show that caffeine,metoprolol,diclofenac,and carbamazepine can be utilized to detect the human impact.They are diluted along the Pearl River,as their concentrations decrease from low salinity towards high salinity.Sulfonamide antibiotics and trimethoprim are suitable to determine the veterinary and human impact.Their highest concentrations were detected along the river yet still in low saline water whereas,the origin of the organic UV-filter is diverse.Their source could not be precisely determined.Only caffeine,metoprolol,octocrylene,and PBSA were detected at the near-coastal stations in the South China Sea.They can be utilized as suitable indicators to detect an anthropogenic impact on the northern South China Sea.The detected concentrations are of low risk to organisms in the Pearl River and the northern South China Sea. | Kathrin Fisch Ruifeng Zhang Meng Zhou Detlef E.Schulz-Bull Joanna J.Waniek | 2021 | Emerging Contaminants2021，7，1： | 3 |
| 19 | Dissection of miRNA Pathways Using Arabidopsis Mesophyll Protoplasts显示文摘主要, post-transcriptionally,由指导,抄本劈开或互补 mRNA 的翻译压抑指向的 MicroRNAs (miRNAs ) 控制基因表示,从而调整的发展进程和压力回答。尽管有这块地的显著扩大,位于 miRNA 活动下面的机制充分没被理解。在这篇文章,我们在 Arabidopsis 叶肉原物描述一个短暂表达式系统,它为 miRNA 小径的解剖是高度顺从的。我们显示出那由短暂地主要 miRNAs 和目标模仿的 overexpressing,我们能操作 miRNA 层次并且因而影响他们的目标。而且,我们为确定开发了一套基于酶的传感器 miRNA 活动对明确地作出回应内长并且 overexpressed miRNAs 和目标模仿。我们证明这些 miRNA 传感器能被用来在特定的变化的 miRNA 活动,以及影响测试 miRNA 小径的通常认为的部件的影响,由 overexpression 或从相应异种的原物的使用。我们进一步证明我们的 miRNA 传感器能被用于在 miRNA 活动调查化学药品的效果。我们的基于房间的短暂表示系统快、容易建立,并且产生量的结果,是为 assaying miRNA 活动在的一个强大的工具 ? vivo。 | Claudia Martinho Ana Confraria Carlos Alexandre Elias Pierre Crozet Ignacio Rubio-Somoza Detlef Weigel Elena Baena-Gonzalez | 2015 | Molecular Plant2015，8，2： | 3 |
| 20 | Hedgehog signaling regulates epithelial-mesenchymal transition during biliary fibrosis in rodents and humans显示文摘 | Omenetti Alessia Porrello Alessandro Jung Youngmi Yang Liu Popov Yury Choi Steve S Witek Rafal P Alpini Gianfranco Venter Juliet Vandongen Hendrika M Syn Wing-Kin Baroni Gianluca Svegliati Benedetti Antonio Schuppan Detlef Diehl Anna Mae | 2008 | Journal of Clinical Investigation2008，，10： | 3 |
您所在的机构暂未开通此部分的功能，请联系管理员