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| 1 | Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases显示文摘Anti-tumor necrosis factor(TNF) antibodies are successfully used in the therapy of inflammatory bowel diseases(IBD). However, the molecular mechanism of action of these agents is still a matter of debate. Apart from neutralization of TNF, influence on the intestinal barrier function, induction of apoptosis in mucosal immune cells, formation of regulatory macrophages as well as other immune modulating properties have been discussed as central features. Nevertheless, clinically effective anti-TNF antibodies were shown to differ in their mode-of-action in vivo and in vitro. Furthermore, the anti-TNF agent etanercept is effective in the treatment of rheumatoid arthritis but failed to induce clinical response in Crohn's disease patients, suggesting different contributions of TNF in the pathogenesis of these inflammatory diseases. In the following, we will review different aspects regarding the mechanism of action of anti-TNF agents in general and analyze comparatively different effects of each antiTNF agent such as TNF neutralization, modulation of the immune system, reverse signaling and induction of apoptosis. We discuss the relevance of the membranebound form of TNF compared to the soluble form for the immunopathogenesis of IBD. Furthermore, we review reports that could lead to personalized medicine approaches regarding treatment with antiTNF antibodies in chronic intestinal inflammation, by predicting response to therapy. | Ulrike Billmeier Walburga Dieterich Markus F Neurath Raja Atreya | 2016 | World Journal of Gastroenterology2016，22，42： | 19 |
| 2 | Colon cancer and the immune system:The role of tumor invading T cells显示文摘Colon cancer is still one of the leading causes of cancer death worldwide. Although the host immune system has been shown to react against tumor cells, mainly through tumor infi ltrating lymphocytes and NK cells, tumor cells may utilize different ways to escape anti-tumor immune response. Tumor infi ltration of CD8+ and CD4+ (T-bet+) effector T cells has been attributed to a beneficial outcome, and the enhancement of T cell activation through T cell receptor stimulation and co-stimulatory signals provides promising strategies for immunotherapy of colon cancer. Growing evidence supports a role for the Fas/FasL system in tumor immunology, although the mechanisms and consequences of FasL activation in colon cancer are not completely understood. In animal models, depletion of regulatory T cells (CD4+ CD25+ T cells) can enhance the anti-tumor immune response under certain conditions. Taken together, recent insights in the immune reaction against colon carcinoma have provided new approaches to immunotherapy, although much remains to be learned about the exact mechanisms. | Maximilian Waldner Carl C Schimanski Markus F Neurath | 2006 | World Journal of Gastroenterology2006，12，45： | 15 |
| 3 | Differential diagnosis in inflammatory bowel disease colitis:State of the art and future perspectives显示文摘Distinction between Crohn's disease of the colonrectum and ulcerative colitis or inflammatory bowel disease(IBD) type unclassified can be of pivotal importance for a tailored clinical management,as each entity often involves specific therapeutic strategies and prognosis.Nonetheless,no gold standard is available and the uncertainty of diagnosis may frequently lead to misclassification or repeated examinations.Hence,we have performed a literature search to address the problem of differential diagnosis in IBD colitis,revised current and emerging diagnostic tools and refined disease classification strategies.Nowadays,the differential diagnosis is an untangled issue,and the proper diagnosis cannot be reached in up to 10% of patients presenting with IBD colitis.This topic is receiving emerging attention,as medical therapies,surgical approaches and leading prognostic outcomes require more and more disease-specific strategies in IBD patients.The optimization of standard diagnostic approaches based on clinical features,biomarkers,radiology,endoscopy and histopathology appears to provide only marginal benefits.Conversely,emerging diagnostic techniques in the field of gastrointestinal endoscopy,molecular pathology,genetics,epigenetics,metabolomics and proteomics have already shown promising results.Novel advanced endoscopic imaging techniques and biomarkers can shed new light for the differential diagnosis of IBD,better reflecting diverse disease behaviors based on specific pathogenic pathways. | Gian Eugenio Tontini Maurizio Vecchi Luca Pastorelli Markus F Neurath Helmut Neumann | 2015 | World Journal of Gastroenterology2015，21，1： | 13 |
| 4 | Capecitabine and irinotecan with and without bevacizumab for advanced colorectal cancer patients显示文摘AIM:To investigate the efficacy and safety of capecitabine plus irinotecan±bevacizumab in advanced or metastatic colorectal cancer patients. METHODS:Forty six patients with previously untreated,locally-advanced or metastatic colorectal cancer(mCRC) were recruited between 2001-2006 in a prospective open-label phaseⅡtrial,in German community-based outpatient clinics.Patients received a standard capecitabine plus irinotecan(CAPIRI) or CAPIRI plus bevacizumab(CAPIRI-BEV) regimen every 3 wk. Dose reductions were mandatory from the first cycle in cases of>grade 2 toxicity.The treatment choice of bevacizumab was at the discretion of the physician.Theprimary endpoints were response and toxicity and secondary endpoints included progression-free survival and overall survival. RESULTS:In the CAPIRI group vs the CAPRI-Bev group there were more female than male patients(47% vs 24%) ,and more patients had colon as the primary tumor site(58.8%vs 48.2%) with fewer patients having sigmoid colon as primary tumor site(5.9%vs 20.7%) .Grade 3/4 toxicity was higher with CAPIRI than CAPIRI-Bev:82%vs 58.6%.Partial response rates were 29.4%and 34.5%,and tumor control rates were 70.6%and 75.9%,respectively.No complete responses were observed.The median progression-free survival was 11.4 mo and 12.8 mo for CAPIRI and CAPIRI-Bev,respectively.The median overall survival for CAPIRI was 15 mo(458 d) and for CAPIRI-Bev 24 mo(733 d) .These differences were not statistically different.In the CAPIRI-Bev,group,two patients underwent a full secondary tumor resection after treatment,whereas in the CAPIRI group no cases underwent this procedure. CONCLUSION:Both regimens were well tolerated and offered effective tumor growth control in this outpatient setting.Severe gastrointestinal toxicities and thromboembolic events were rare and if observed were never fatal. | Markus Moehler Martin F Sprinzl Murad Abdelfattah Carl C Schimanski Bernd Adami Werner Godderz Klaus Majer Dimitri Flieger Andreas Teufel Juergen Siebler Thomas Hoehler Peter R Galle Stephan Kanzler | 2009 | World Journal of Gastroenterology2009，15，4： | 10 |
| 5 | Double-balloon-enteroscopy-based endoscopic retrograde cholangiopancreatography in post-surgical patients显示文摘AIM: To evaluate double balloon enteroscopy (DBE) in post-surgical patients to perform endoscopic retrograde cholangiopancreatography (ERCP) and interventions. METHODS: In 37 post-surgical patients, a stepwise approach was performed to reach normal papilla or enteral anastomoses of the biliary tract/pancreas. When conventional endoscopy failed, DBE-based ERCP was performed and standard parameters for DBE, ERCP and interventions were recorded. RESULTS: Push-enteroscopy (overall, 16 procedures) reached enteral anastomoses only in six out of 37 post-surgical patients (16.2%). DBE achieved a high rate of luminal access to the biliary tract in 23 of the remaining 31 patients (74.1%) and to the pancreatic duct (three patients). Among all DBE-based ERCPs (86 procedures), 21/23 patients (91.3%) were successfully treated. Interventions included ostium incision or papillotomy in 6/23 (26%) and 7/23 patients (30.4%), respectively. Biliary endoprosthesis insertion and regular exchange was achieved in 17/23 (73.9%) and 7/23 patients (30.4%), respectively. Furthermore, bile duct stone extraction as well as ostium and papillary dilation were performed in 5/23 (21.7%) and 3/23 patients (13.0%), respectively. Complications during DBE-based procedures were bleeding (1.1%), perforation (2.3%) and pancreatitis (2.3%), and minor complications occurred in up to 19.1%. CONCLUSION: The appropriate use of DBE yields a high rate of luminal access to papilla or enteral anastomoses in more than two-thirds of post-surgical patients, allowing important successful endoscopic therapeutic interventions. | Martin Raithel Harald Dormann Andreas Naegel Frank Boxberger Eckhart G Hahn Markus F Neurath Juergen Maiss | 2011 | World Journal of Gastroenterology2011，17，18： | 9 |
| 6 | Advances in hepatitis C therapy: What is the current state-what come's next?显示文摘Chronic hepatitis C virus(HCV) infection affects 80-160 million people worldwide and is one of the leading causes of chronic liver disease.It is only a few years ago that standard treatment regimes were based on pegylated interferon alpha and ribavirin.However,treatment of HCV has undergone a revolutionary change in recent years.The admission of the nucleotide polymerase inhibitor Sofosbuvir enabled an interferon-free regimen with direct antiviral agents(DAA).Meanwhile seven DAAs are available and can be applied in several combinations for 8 to 24 wk depending on HCV genotype and patient characteristics such as cirrhosis and chronic renal failure.High rates of sustained virological response(SVR) rates can be achieved with these novel drugs.Even in difficult to treat populations such as patients with liver cirrhosis,HCV-human immunodeficiency virus co-infections,after liver transplantion,or with chronic kidney disease comparable high rates of SVR can be achieved.The anticipated 2nd generation DAAs are strikingly effective in patients so far classified as difficult to treat including decompensated liver cirrhosis or posttransplant patients.These 2nd generations DAAs will have higher resistance barriers,higher antiviral effects and a pan-genotypic spectrum.This review highlights the current state of the art of antiviral treatment in hepatitis Cand gives an outlook for upcoming therapies. | Steffen Zopf Andreas E Kremer Markus F Neurath Juergen Siebler | 2016 | World Journal of Hepatology2016，8，3： | 7 |
| 7 | Sporadic versus hereditary gastrinomas of the duodenum and pancreas: Distinct clinico-pathological and epidemiological features显示文摘Gastrinomas are defined as gastrin secreting tumors that are associated with Zollinger-Ellison syndrome (ZES). ZES is characterized by elevated fasting gastrin serum levels, positive secretin stimulation test and clinical symptoms such as recurrent peptic ulcer disease, gastroesophageal re?ux disease and occasional diarrhea. Genetically, nonhereditary (sporadic) gastrinomas are distinguished from hereditary gastrinomas, which are associated with multiple endocrine neoplasia type 1 (MEN1) syndrome. In general, duodenal gastrinomas are small and solitary if they are sporadic and multiple as well as hereditary. The sporadic gastrinomas occur in the duodenum or in the pancreas while the hereditary gastrinomas almost all occur in the duodenum. Our series of 77 sporadic duodenal neuroendocrine tumors (NETs) includes 18 patients (23.4%) with gastrinomas and ZES. Of 535 sporadic NETs in the pancreas collected from the NET archives of the departments of pathology in Zürich, Switzerland, and Kiel, Germany, 24 patients (4.5%) suffered from sporadic pancreatic gastrinomas and ZES. These NETs have to be distinguished fromtumors with immunohistochemical positivity for gastrin but without evidence of ZES. An additional 19 patients suffered from MEN1 and ZES. These patients showed exclusively duodenal gastrinomas, but not pancreatic gastrinomas. The prognosis of sporadic and MEN1- associated duodenal gastrinomas is better than that of pancreatic gastrinomas, since they progress slowly to liver metastasis. In summary, sporadic and MEN1- associated gastrinomas in the duodenum and pancreas show different clinico-pathological and genetic features. The incidence of sporadic duodenal gastrin-producing tumors is increasing, possibly due to optimized diagnostic procedures. In contrast, pancreatic MEN1- associated gastrinomas seem to be extremely rare. A considerable subset of tumors with immunohistochemical expression of gastrin but without evidence of ZES should be designated as functionally inactive NETs expressing gastrin, but not as gastrinomas. | Martin Anlauf Nele Garbrecht Tobias Henopp Anja Schmitt Regina Schlenger Andreas Raffel Markus Krausch Oliver Gimm Claus F Eisenberger Wolfram T Knoefel Henning Dralle Paul Komminoth Philipp U Heitz Aurel Perren Günter Klppel | 2006 | World Journal of Gastroenterology2006，12，34： | 7 |
| 8 | Cancer risk in IBD: How to diagnose and how to manage DALM and ALM显示文摘The risk of developing neoplasia leading to colorectal cancer is significantly increased in ulcerative colitis (UC) and most likely in Crohn's disease. Several endoscopic surveillance strategies have been implemented to identify these lesions. The main issue is that colitisassociated neoplasms often occurs in flat mucosa, often being detected on taking random biopsies rather than by identification of these lesions via endoscopic imaging. The standard diagnostic procedure in long lasting UC is to take four biopsies every 10 cm. Image enhancement methods, such as chromoendoscopy and virtual histology using endomicroscopy, have greatly im- proved neoplasia detection rates and may contribute toreduced random biopsies by taking targeted 'smart' biopsies. Chromoendoscopy may effectively be performed by experienced endoscopists for routine screening of UC patients. By contrast, endomicroscopy is often only available in selected specialized endoscopic centers. Importantly, advanced endoscopic imaging has the poten- tial to increase the detection rate of neoplasia whereas the interplay between endoscopic experience and interpretation of histological biopsy evaluation allows the physician to make a proper diagnosis and to find the appropriate therapeutic approach. Colitis-associated intraepithelial neoplasms may occur in flat mucosa of endoscopically normal appearance or may arise as dysplasia-associated lesion or mass (DALM), which may be indistinguishable from sporadic adenomas in healthy or non-colitis mucosa [adenoma-like mass (ALM)]. The aim of this review was to summarize endoscopic and histological characteristics of DALM and ALM in the context of therapeutic procedures. | Helmut Neumann Michael Vieth Cord Langner Markus F Neurath Jonas Mudter | 2011 | World Journal of Gastroenterology2011，17，27： | 6 |
| 9 | In vivo subsurface morphological and functional cellular and subcellular imaging of the gastrointestinal tract with confocal mini-microscopy显示文摘瞄准:为在活体内评估一根最新发达的手持的共焦的探针在啮齿类动物的完全的胃肠道的显微镜的成像。方法:一根新奇僵硬共焦的探针(直径 7 公里) 为 fluorophore 刺激用 488 nm 单身者线激光在人为使用与类似于灵活 endomicroscopy 系统的光特征被设计。轻排放在 505 ~ 750 nm 被检测。看法的地多样地是 475 妈妈 475 妈妈。光片厚度是有 0.7 妈妈的侧面的分辨率的 7 妈妈。在不同深度(到 250 妈妈的表面) 的表面下的连续图象多样地在 1024 点在实时被产生由在轻轻的、稳定的接触把探查放到织物上的 1024 个象素(0.8 frames/s ) 。织物标本为组织病理学说的关联被取样。结果:食管,胃,小并且大肠和中央,肝,胰和胆囊是在在 n = 的高分辨率的视觉 ised 在活体内 48 个鼠标。有共焦的微型显微镜学探查的实时显微镜的成像是容易的完成。不同染色协议(荧光黄,吖啶黄,标记 FITC 的葡聚糖和 L。可食用嗯植物凝血素) 织物的每个加亮的特定的方面,和在活体内成像与常规组织学最优地相关。在活体内血流监视把功能的质量加到词法成像。结论:共焦的显微镜学是在甚至表面下的织物结构的高分辨率允许完全的官方补给的道的可视化的可行在活体内。在这研究评估的新共焦的探查设计与腹腔镜检查兼容并且显著地扩展可能的应用的地到 intra 腹的机关。它允许新在活体内染色和申请选择的立即的测试因此在病人从动物研究允许快速的转移到临床的使用。 | Martin Goetz Beena Memadathil Stefan Biesterfeld Constantin Schneider Sebastian Gregor Peter R Galle Markus F Neurath Ralf Kiesslich | 2007 | World Journal of Gastroenterology2007，13，15： | 6 |
| 10 | New endoscopic approaches in IBD显示文摘Recent advances in endoscopic imaging techniques have revolutionized the diagnostic approach of patients with inflammatory bowel disease(IBD).New,emerging endoscopic imaging techniques visualized a plethora of new mucosal details even at the cellular and subcellular level.This review offers an overview about new endoscopic techniques,including chromoendoscopy,magnification endoscopy,spectroscopy,confocal laser endomicroscopy and endocytoscopy in the face of IBD. | Helmut Neumann Markus F Neurath Jonas Mudter | 2011 | World Journal of Gastroenterology2011，17，1： | 6 |
| 11 | First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy显示文摘We present the case of a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNF antibodies(infliximab, adalimumab) and tacrolimus, who refused colectomy as a therapeutic option. As the pro-inflammatory cytokine interleukin-6(IL-6) had been identified as a crucial regulator in the immunopathogenesis of inflammatory bowel diseases, we treated the patient with biweekly intravenous infusions of an anti-IL-6R antibody(tocilizumab) for 12 wk. However, no clinical improvement of disease activity was noted. In fact, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of mucosal inflammation and ulcer formation upon anti-IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines such as TNF, IL-21 and IFN-γ. Inhibition of IL-6 by tocilizumab had no clinical benefit in this patient with intractable ulcerative colitis and even led to exacerbation of mucosal inflammation. Our findings suggest that anti-IL-6R antibody therapy may leadto aggravation of anti-TNF resistant ulcerative colitis. When targeting IL-6, the differential responsiveness of target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inflammation via soluble IL-6R signaling but on the other side also strongly contributes to epithelial cell survival via membrane bound IL-6R signaling. | Raja Atreya Ulrike Billmeier Timo Rath Jonas Mudter Michael Vieth Helmut Neumann Markus F Neurath | 2015 | World Journal of Gastroenterology2015，21，45： | 5 |
| 12 | EV和HEV的爪形离合器变速器显示文摘电动汽车是在减少对化石燃料依赖和环境污染的同时,确保人类移动灵活性和实现汽车产业可持续发展的有效路径。在中国,通过”九五”、“十五”和”十一五”期间国家科技计划的持续支持和能源基金组织等国际社会的帮助,电动汽车技术的开发及产业化工作得以不断深入,并得到国际社会的广泛认可。 | Markus Schnablerhofer f&e | 2012 | 汽车零部件2012，，10： | 4 |
| 13 | Comparison of Hemospray~? and Endoclot? for the treatment of gastrointestinal bleeding显示文摘BACKGROUND Gastrointestinal(GI) bleeding is a common indication for endoscopy. For refractory cases, hemostatic powders(HP) represent 'touch-free' agents.AIM To analyze short term(ST-within 72 h-) and long-term(LT-within 30 d-) success for achieving hemostasis with HP and to directly compare the two agents Hemospray(HS) and Endoclot(EC).METHODS HP was applied in 154 consecutive patients(mean age 67 years) with GI bleeding.Patients were followed up for 1 mo(mean follow-up: 3.2 mo).RESULTS Majority of applications were in upper GI tract(89%) with following bleeding sources: peptic ulcer disease(35%), esophageal varices(7%), tumor bleeding(11.7%), reflux esophagitis(8.7%), diffuse bleeding and erosions(15.3%). Overall ST success was achieved in 125 patients(81%) and LT success in 81 patients(67%). Re-bleeding occurred in 27% of all patients. In 72 patients(47%), HP was applied as a salvage hemostatic therapy, here ST and LT success were 81% and64%, with re-bleeding in 32%. As a primary hemostatic therapy, ST and LT success were 82% and 69%, with re-bleeding occurring in 22%. HS was more frequently applied for upper GI bleeding(P = 0.04)CONCLUSION Both HP allow for effective hemostasis with no differences in ST, LT success and re-bleeding. | Francesco Vitali Andreas Naegel Raja Atreya Steffen Zopf Clemens Neufert Juergen Siebler Markus F Neurath Timo Rath | 2019 | World Journal of Gastroenterology2019，25，13： | 2 |
| 14 | Infectious, atopic and inflammatory diseases, childhood adversities and familial aggregation are independently associated with the risk for mental disorders: Results from a large Swiss epidemiological study显示文摘AIM To examine the associations between mental disorders and infectious, atopic, inflammatory diseases while adjusting for other risk factors.METHODS We used data from PsyC oL aus, a large Swiss Population Cohort Study(n = 3720; age range 35-66). Lifetime diagnoses of mental disorders were grouped into the following categories: Neurodevelopmental, anxiety(early and late onset), mood and substance disorders. They were regressed on infectious, atopic and other inflammatory diseases adjusting for sex, educational level, familial aggregation, childhood adversities and traumatic experiences in childhood. A multivariate logistic regression was applied to each group of disorders. In a complementary analysis interactions with sex were introduced via nested effects. RESULTS Associations with infectious, atopic and other chronic inflammatory diseases were observable together with consistent effects of childhood adversities and familial aggregation, and less consistent effects of trauma in each group of mental disorders. Streptococcal infections were associated with neurodevelopmental disorders(men), and measles/mumps/rubella-infections with early and late anxiety disorders(women). Gastric inflammatory diseases took effect in mood disorders(both sexes) and in early disorders(men). Similarly, irritable bowel syndrome was prominent in a sex-specific way in mood disorders in women, and, moreover, was associated with early and late anxiety disorders. Atopic diseases were associated with late anxiety disorders. Acne(associations with mood disorders in men) and psoriasis(associations with early anxiety disorders in men and mood disorders in women) contributed sex-specific results. Urinary tract infections were associated with mood disorders and, in addition, in a sex-specific way with late anxiety disorders(men), and neurodevelopmental and early anxiety disorders(women).CONCLUSION Infectious, atopic and inflammatory diseases areimportant risk factors for all groups of mental disorders. The sexual dimorphism of the associations is pronounced. | Vladeta Ajdacic-Gross Aleksandra Aleksandrowicz Stephanie Rodgers Margot Mutsch Anja Tesic Mario Müller Wolfram Kawohl Wulf R?ssler Erich Seifritz Enrique Castelao Marie-Pierre F Strippoli Caroline Vandeleur Roland von K?nel Rosa Paolicelli Markus A Landolt Cornelia Witthauer Roselind Lieb Martin Preisig | 2016 | World Journal of Psychiatry2016，6，4： | 2 |
| 15 | RAPD variation among and within small and large populations of the rare clonal plant Ranunculm reptans(Ranuneulaeeae ) 显示文摘 | MARKUS F RENE H DANIEL P | 2000 | American Journal of Botany2000，87，： | 1 |
| 16 | Incorporating a statistically based shape model into a system for computor-assisted anterior cruciate ligament surgery显示文摘 | Markus F St(e)phane L R(e)mi J | 1999 | Medical Image Analysis1999，3，3： | 1 |
| 17 | Hofreither,Phasing out of environmentally harmful sidies:Consequences of the 2003 CAP reform显示文摘 | Erwin Schmida Franz Sinabell Markus F | 2003 | Ecological Econpmics2003，，： | 1 |
| 18 | Pyridinyl polythiazole class peptide antiriotic microtic micrococcin pi, Secreted by foodbornh staphylococcus e guorm Ws2733, is biosynthesized nonribosomally显示文摘 | Markus C C Torsten S Kevin P F | 2001 | Eu J Biochem2001，268，： | 1 |
| 19 | Nymphal RNAi:Systemic RNAi Mediated Gene Knockdown in Juvenile Grasshopper显示文摘 | DONG Y MARKUS F | 2005 | BMC Biotechnology2005，5，25： | 1 |
| 20 | 显示文摘 | Finotto S Markus F Neurath MF | 2002 | Science2002，295，： | 1 |
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