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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 | Managementofearlyasymptomaticgastrointestinalstromaltumorsofthe stomach显示文摘Gastrointestinal stromal tumors(GIST) are the most common mesenchymal tumors of the digestive tract. Approximately two thirds of clinically manifest tumors occur in the stomach, nearly one third in the small bowel, and the rest in the colorectal region with a few cas-es in the esophagus. GIST originate within the smooth muscle layer in the wall of the tubular gastrointestinal tract and grow mostly toward the serosa, far less often toward the mucosa. In the latter case, ulceration may develop and can cause gastrointestinal bleeding as the cardinal symptom. However, most GIST of the stomach are asymptomatic. They are increasingly detected incidentally as small intramural or submucosal tumors during endoscopy and particularly during endoscopic ultra-sound. Epidemiological and molecular genetic findings suggest that early asymptomatic GIST of the stomach(< 1 cm) show self-limiting tumorigenesis. Thus, early(< 1 cm) asymptomatic gastric GIST(synonym: micro-GIST) are found in 20%-30% of the elderly. The mostlyelderly people with early gastric GIST have an excellent GIST-specific prognosis. Patients with early GIST of the stomach can therefore be managed by endoscopic sur-veillance. | Scherübl H Faiss S Knoefel WT Wardelmann E | 2014 | World Journal of Gastrointestinal Endoscopy2014，6，7： | 23 |
| 3 | Clinically detected gastroenteropancreatic neuroendocrine tumors are on the rise: Epidemiological changes in Germany显示文摘AIM:To study the epidemiologic changes of gastroenteropancreatic neuroendocrine tumors(GEP-NET)in Germany,we analyzed two time periods 1976-1988 and1998-2006.METHODS:We evaluated epidemiological data of GEP-NET from the former East German National Cancer Registry(DDR Krebsregister,1976-1988)and its successor,the Joint Cancer Registry(GKR,1998-2006),which was founded after German reunification.Due to a particularly substantial database the epidemiological data from the federal states of Mecklenburg-Western Pomerania,Saxony,Brandenburg and Thuringia,covering a population of more than 10.8 million people,were analyzed.Survival probabilities were calculated using life table analysis.In addition,GEP-NET patients were evaluated for one or more second(non-GEP-NET)primary malignancies.RESULTS:A total of 2821 GEP neuroendocrine neoplasms were identified in the two registries.The overall incidence increased significantly between 1976 and2006 from 0.31(per 100.000 inhabitants per year)to2.27 for men and from 0.57 to 2.38 for women.In the later period studied(2004-2006),the small intestine was the most common site.Neuroendocrine(NE)neoplasms of the small intestine showed the largest absolute increase in incidence,while rectal NE neoplasms exhibited the greatest relative increase.Only the incidence of appendiceal NET in women showed little change between 1976 and 2006.Overall survival of patients varied for sex,tumor site and the two periods studied but improved significantly over time.Interestingly,about 20%of the GEP-NET patients developed one or more second malignancies.Their most common location was the gastrointestinal tract.GEP-NET patients without second malignancies fared better than those with one or more of them.CONCLUSION:The number of detected GEP-NET increased about 5-fold in Germany between 1976 and2006.At the same time,their anatomic distribution changed,and the survival of GEP-NET patients improved significantly.Second malignancies are common and influence the overall survival of GEP-NET patients.Thus,GEP-NET warrant our attention as well as intensive research on their tumorigenesis. | Hans Scherübl Brigitte Streller Roland Stabenow Hermann Herbst Michael Hopfner Christoph Schwertner Joachim Steinberg Jan Eick Wanda Ring Krishna Tiwari Soren M Zappe | 2013 | World Journal of Gastroenterology2013，19，47： | 16 |
| 4 | Management of early gastrointestinal neuroendocrine neoplasms显示文摘Neuroendocrine neoplasms (NENs) of the stomach, duo- denum, appendix or rectum that are small (≤ 1 cm) and well differentiated can be considered 'early' tumors, since they generally have a (very) good prognosis. In the new WHO classification of 2010, these neoplasms are called neuroendocrine tumors/ carcinoids (NETs), grade (G) 1 or 2, and distinguished from poorly differentiated neuroendocrine carcinomas (NECs), G3. NETs are increasing, with a rise in the age-adjusted incidence in the U.S.A. by about 700 % in the last 35 years. Improved early detection seems to be the main reason for these epidemiological changes. Both the better generalavailability of endoscopy, and imaging techniques, have led to a shift in the discovery of smaller-sized (≤ 10-20 mm) intestinal NETs/carcinoids and earlier tumor stages at diagnosis. Endoscopic screening is therefore effective in the early diagnosis, not only of colorectal adenocarcinomas, but also of NETs/carcinoids. Endoscopic removal, followed up with endoscopic surveillance is the treatment of choice in NETs/carcinoids of the stomach, duodenum and rectum that are ≤ 10 mm in size, have a low proliferative activity (G1), do not infiltrate the muscular layer and show no angioinvasion. In all the other intestinal NENs, optimal treatment generally needs surgery and/or medical therapy depending on type, biology and stage of the tumor, as well as the individual situation of the patient. | Hans Scherübl Robert T Jensen Guillaume Cadiot Ulrich Stlzel Günter Klppel | 2011 | World Journal of Gastrointestinal Endoscopy2011，3，7： | 13 |
| 5 | 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 |
| 6 | 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 |
| 7 | Neuroendocrine tumors of the small bowels are on the rise:Early aspects and management显示文摘Neuroendocrine tumors of the small bowel are on the rise. In the US they have increased by 300%-500% in the last 35 years. At the same time their prognosis is much improved. Today,most neuroendocrine tumors (NETs) of the duodenum are detected 'incidentally' and therefore recognized at an early stage. Duodenal NETs which are well differentiated,not larger than 10 mm and limited to the mucosa/submucosa can be endoscopically resected. The management of duodenal NETs ranging between 10 and 20 mm needs an interdisciplinary discussion. Endoscopic ultrasound is the method of choice to determine tumor size and depth of infiltration. Surgery is recommended for well-differentiated duodenal NET tumors greater than 20 mm,for localized sporadic gastrinomas (of any size) and for localized poorly differentiated NE cancers. Surgery is recommended for any ileal NET. Advanced ileal NETs with a carcinoid syndrome are treated with longacting somatostatin analogs. This treatment significantly improves (progression-free) survival in patients with metastatic NETs of the ileum. For optimal NET management,tumor biology,type,localization and stage of the neoplasm,as well as the patient's individual circumstances have to be taken into account. | Hans Scherbl Robert T Jensen Guillaume Cadiot Ulrich Stlzel Gnter Klppel | 2010 | World Journal of Gastrointestinal Endoscopy2010，2，10： | 10 |
| 8 | 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 |
| 9 | 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 |
| 10 | Search for a dark photon in the π 0 → e + e ? γ decay显示文摘 | P. Adlarson W. Augustyniak W. Bardan M. Bashkanov F.S. Bergmann M. Ber?owski H. Bhatt A. Bondar M. Büscher H. Calén I. Ciepa? H. Clement D. Coderre E. Czerwiński K. Demmich E. Doroshkevich R. Engels W. Erven W. Eyrich P. Fedorets K. F?hl K. Fransson F. Go | 2013 | Physics Letters B . 2013 (1-3)2013，，1： | 3 |
| 11 | 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 |
| 12 | Neuroendocrine tumors of the stomach (gastric carcinoids) are on the rise: small tumors, small problems?显示文摘 | H. Scherübl G. Cadiot R. Jensen T. R?sch U. St?lzel G. Kl?ppel | 2010 | Endoscopy2010，，08： | 3 |
| 13 | Endoscopic right thyroid lobectomy显示文摘 | M. M. Lirici C. S. G. Hüscher S. Chiodini C. Napolitano A. Recher | 1997 | Surgical Endoscopy1997，，8： | 2 |
| 14 | p27 as a target for cancer therapeutics 显示文摘 | Blain SW Scher HI Cordon-Cardo C | 2003 | Cancer Cell2003，3，2： | 2 |
| 15 | 在接受治疗的急性冠状动脉综合征患者中,肌钙蛋白峰值与长期缺血事件之间的关系显示文摘非ST段抬高急性冠状动脉综合征(acutecoro-narysyndromes,ACS)患者肌钙蛋白水平与结局的关系虽然已经明确,但接受抗血小板治疗管理的非ST段抬高ACS患者肌钙蛋白水平与长期结局的关系尚未明确。 | 刘莉 叶鹏 Goldstein SA Newby LK Cyr DD Neely M Lüscher TF Brown EB White HD Ohman EM Roe MT Hamm CW | 2017 | 中华高血压杂志2017，25，5： | 2 |
| 16 | 内皮细胞在冠状动脉张力调节中的作用显示文摘自1980年Furchgott和Zawadzki首先报道内皮细胞在血管张力变化中的作用以来,该领域的研究有了很大进展。现已证实,内皮细胞调节血管张力的主要机制是合成和释放血管松弛因子(EDRF)及收缩因子(EDCF)。本文旨在回顾近年来的主要研究成果,并重点阐述内皮细胞在冠状动脉(冠脉)张力调节中的作用。 | 王乐信 Thomas F.Lüscher | 1992 | 中国循环杂志1992，7，3： | 2 |
| 17 | Molecular mechanisms of vascular effects of High‐density lipoprotein: alterations in cardiovascular disease显示文摘 | ChristianBesler Thomas F.Lüscher UlfLandmesser | 2012 | EMBO Mol Med2012，，4： | 2 |
| 18 | Raman shifts in Si nanocrystals显示文摘 | ZI J BU SCHER H FALTER C | 1996 | Applied Physics Letters1996，69，2： | 1 |
| 19 | The predictive value of indium - 111 leukocyte scans in the diagnosis of infected total hip, knee, or resection arthroplasties显示文摘 | Scher D M Pak K Lonner J H | 2000 | J Arthroplasty2000，15，3： | 1 |
| 20 | Histologic evaluation of nail clippings for diagnosing onychomycosis显示文摘 | Silvers DN Scher RK | 1991 | Arch Dermatol1991，127，： | 1 |
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