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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 | 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 |
| 3 | Confocal laser endomicroscopy for the differential diagnosis of ulcerative colitis and Crohn’s disease: a pilot study显示文摘 | Gian Tontini Jonas Mudter Michael Vieth Raja Atreya Claudia Günther Yurdagül Zopf Dane Wildner Ralf Kiesslich Maurizio Vecchi Markus Neurath Helmut Neumann | 2014 | Endoscopy2014，，： | 2 |
| 4 | 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 |
| 5 | Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600–Mutant Colorectal Cancer显示文摘 | Corcoran Ryan B. Atreya Chloe E. Falchook Gerald S. Kwak Eunice L. Ryan David P. Bendell Johanna C. Hamid Omid Messersmith Wells A. Daud Adil Kurzrock Razelle Pierobon Mariaelena Sun Peng Cunningham Elizabeth Little Shonda Orford Keith Motwani Monica Bai | 2015 | Journal of Clinical Oncology2015，，34： | 2 |
| 6 | Detection of methane in the atmosphere of mars显示文摘 | Formisano V Atreya S Encrenaz T | 2004 | Science2004，306，： | 1 |
| 7 | Study:Temperature and residual stress in an injection moulded gear显示文摘 | KANSAL G RAO P N ATREYA S K | 2001 | Journal of Materials Processing Technology2001，108，： | 1 |
| 8 | NF-kappaB in inflammatory bowel disease 显示文摘 | Atreya I Atreya R Neumth M F | 2008 | J Intern Med2008，263，6： | 1 |
| 9 | Heat and mass transfer during piloted ignition of cellulosic solids显示文摘 | ATREYA A WICHMAN I S | 1989 | Journal of Heat Transfer1989，111，： | 1 |
| 10 | A point mutation in the coat protein abolishes aphid transmisibility of a potyvirus 显示文摘 | Atreya C D Raccah B Pieron T P | 1990 | Virology1990，178，： | 1 |
| 11 | Development of bio-climatic zones in north-east India显示文摘 | Singh Manoj Kumar Mahapatra Sadhan Atreya S K | 2007 | Energy and Buildings2007，39，12： | 1 |
| 12 | NF-kappaB in inflammatory bowel disease显示文摘 | Atreya I Atreya R Neurath MF | 2008 | j Intern Med2008，263，6： | 1 |
| 13 | Chemical sources of haze formation in Titan' s atmosphere显示文摘 | Wilson E H Atreya S K | 2003 | Planet Space Sci2003，51，： | 1 |
| 14 | Involvement of 1L-6 in the pathogenesis of inflammatory bowel disease and Colon cancer 显示文摘 | Atreya R Neurath MF | 2005 | Clin Rev Allergy Immunol2005，28，3： | 1 |
| 15 | A simplified model for pyrolysis of charring materials 显示文摘 | WICHMANI S ATREYA A | 1987 | Combustion and Flame1987，68，： | 1 |
| 16 | Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in crohn disease and experimental colitis in vivo显示文摘 | Atreya R Mudter J Finotto S | 2000 | Nat Med2000，6，5： | 1 |
| 17 | Mutational analysis of the pelper component proteinase gene of a potyvirus:effects of amino acid substitutions,deletions,and gene replacement on virulence and aphid transmissibility显示文摘 | ATREYA C D PIRONE T P | 1993 | Proceedings of the National Academy USA1993，90，11： | 1 |
| 18 | NF-kappaB in inflammatory bowel disease显示文摘 | Atreya I Atreya R Neurath M F | 2008 | J Intern Med2008，263，6： | 1 |
| 19 | Sooting Structure of Methane Counterflow Diffusion Flames With Preheated Reactants and Dilution by Products of Combustion 显示文摘 | Zhang C Atreya A Lee K | 1992 | Proceedings of the Combustion Institute1992，24，1： | 1 |
| 20 | NF-kappaB in inflammatory bowel disease显示文摘 | ATREYA I ATREYA R NEURATH MF | 2008 | J Intern Med2008，263，： | 1 |
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