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| 1 | Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25显示文摘堵住抗体 ipilimumab 的细胞毒素的 T 淋巴细胞 antigen-4 (CTLA-4 ) 在很少的病人导致变形黑瘤的调停免疫者的长期的控制。尽管 ipilimumab 无疑经由 immunostimulation 施加它的治疗学的效果,这样远的临床上有用的、 immunologically 相关的 biomarkers 预言治疗效率是逃犯的。这里,我们显示出 IL-2 的那中立化或堵住 α并且 βIL-2 受体的子单元(CD25 和 CD122,分别地) 否则在现出症状之前的潜的老鼠模型由 CTLA-4 封锁导致了,废除了 antitumor 效果和 intratumoral T 受动器对规章的房间(Tregs ) 的比率的伴随的改进,它是。CTLA-4 封锁导致了在失去了 FoxP3 表示并且在 regressing 肿瘤积累了的 IL-2-producing 受动器房间与伴随物上升表示 Lag3, ICOS, IL-10 和 Egr2 的一个镇压 CD4 + T 房间子集的减小。当 recombinant IL-2 改进了 CTLA-4 封锁的治疗学的功效时,圈套 IL-2 受体 α(IL-2Rα, sCD25 ) 禁止了 CTLA-4 的 anticancer 效果封锁。在收到 ipilimumab 的 262 个变形黑瘤病人, sCD25 的基线浆液集中代表了全面幸存的独立指示物,与预言到治疗的抵抗的高水平。总的来说,这些结果解开为在 CTLA-4 的 anticancer 活动的 IL-2 和 IL-2 受体的一个角色封锁。重要地,我们的学习提供第一 immunologically 相关的 biomarker,也就是提高的浆液 sCD25,那与黑瘤在病人预言抵抗到 CTLA-4 封锁。 | Dalil Hannani Marie Vetizou David Enot Sylvie Rusakiewicz Nathalie Chaput David Klatzmann Melanie Desbois Nicolas Jacquelot Nadege Vimond Salem Chouaib Christine Mateus James P Allison Antoni Ribas Jedd D Wolchok Jianda Yuan Philip Wong Michael Postow Andrzej Mackiewicz Jacek Mackiewicz Dirk Schadendorff Dirk Jaeger Alan J Korman Keith Bahjat Michele Maio Luana Calabro Michele WL Teng Mark J Smyth Alexander Eggennont Caroline Robert Guido Kroemer Laurence Zitvogel | 2015 | Cell Research2015，25，2： | 14 |
| 2 | On tolerability and safety of a maintenance treatment with 6-thioguanine in azathioprineor 6-mercaptopurine intolerant IBD patients显示文摘AIM: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 year.METHODS: Database analysis.RESULTS: Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8×108 RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%)and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had splenomegaly.CONCLUSION: The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials. | Nanne KH de Boer Luc JJ Derijks Lennard PL Gilissen Daniel W Hommes Leopold GJB Engels Sybrand Y de Boer Gijsbertus den Hartog Piet M Hooymans Anja BU M(?)kelburg Barend D Westerveld Anton HJ Naber Chris JJ Mulder Dirk J de Jong | 2005 | World Journal of Gastroenterology2005，11，35： | 4 |
| 3 | Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind randomised phase 3 study显示文摘 | Hedy L Kindler Tatsuya Ioka Dirk J Richel Jaafar Bennouna Richard Létourneau Takuji Okusaka Akihiro Funakoshi Junji Furuse Young Suk Park Shinichi Ohkawa Gregory M Springett Harpreet S Wasan Peter C Trask Paul Bycott Alejandro D Ricart Sinil Kim Eric Van | 2011 | Lancet Oncology2011，，3： | 4 |
| 4 | Frequent amplification of a chr19q13.41 microRNA polycistron in aggressive primitive neuroectodermal brain tumors显示文摘 | Li M Lee KF Lu Y Clarke I Shih D Eberhart C Collins VP Van Meter T Picard D Zhou L Boutros PC Modena P Liang ML Scherer SW Bouffet E Rutka JT Pomeroy SL Lau CC Taylor MD Gajjar A Dirks PB Hawkins CE Huang A. | 2009 | 中国神经肿瘤杂志2009，7，4： | 3 |
| 5 | Early Mucosal Healing With Infliximab Is Associated With Improved Long-term Clinical Outcomes in Ulcerative Colitis显示文摘 | Jean Frédéric Colombel Paul Rutgeerts Walter Reinisch Dirk Esser Yanxin Wang Yinghua Lang Colleen W. Marano Richard Strauss Bj?rn J. Oddens Brian G. Feagan Stephen B. Hanauer Gary R. Lichtenstein Daniel Present Bruce E. Sands William J. Sandborn | 2011 | Gastroenterology2011，，4： | 3 |
| 6 | Lack of correlation between Treg quantification assays in inflammatory bowel disease patients显示文摘AIM:To compare the number of regulatory T-cells( Tregs) measured by flow cytometry with those obtained using a real-time quantitative PCR(q PCR) method in patients suffering from inflammatory bowel disease(IBD).METHODS:Tregs percentages obtained by both flow cytometry and q PCR methods in 35 adult IBD patients,18 out of them with Crohn′s disease(CD)and 17 with ulcerative colitis(UC)were compared to each other as well as to scores on two IBD activity questionnaires using the Harvey Bradshaw Index(HBI)for CD patients and the Simple Colitis Clinical Activity Index(SCCAI)for UC patients.The Treg percentages by flow cytometry were defined as CD4+CD25highCD127lowFOXP3+cells in peripheral blood mononuclear cells,whereas the Treg percentages by q PCR method were determined as FOXP3 promoter demethylation in genomic DNA.RESULTS:We found an average of 1.56%±0.78%Tregs by using flow cytometry,compared to 1.07%±0.53%Tregs by using q PCR in adult IBD patients.There were no significant correlations between either the percentages of Tregs measured by flow cytometry or q PCR and the HBI or SCCAI questionnaire scores in CD or UC patients,respectively.In addition,there was no correlation between Treg percentages measured by q PCR and those measured by flow cytometry(r=-0.06,P=0.73;Spearman Rho).These data suggest that,either Treg-related immune function or the clinical scores in these IBD patients did not accurately reflect actual disease activity.Until the cause(s)for these differences are more clearly defined,the resultssuggest caution in interpreting studies of Tregs in various inflammatory disorders.CONCLUSION:The two methods did not produce equivalent measures of the percentage of total Tregs in the IBD patients studied which is consistent with the conclusion that Tregs subtypes are not equally detected by these two assays. | Gunnar Brandhorst Darinka Todorova Petrova Sebastian Weigand Christoph Eberle Nicolas von Ahsen Jessica Schmitz Frank Christian Schultze Dirk Raddatz Michael Karaus Michael Oellerich Philip D Walson | 2015 | World Journal of Gastroenterology2015，21，11： | 2 |
| 7 | Treatment of small-bowel fistulae in the open abdomen with topical negative-pressure therapy显示文摘 | Mathieu D’Hondt Dirk Devriendt Frank Van Rooy Franky Vansteenkiste André D’Hoore Freddy Penninckx Marc Miserez | 2011 | The American Journal of Surgery2011，，： | 2 |
| 8 | Difference method for analysing infrared images in pigs with elevated body temperatures显示文摘 | Carsten Siewert Sven D?nicke Susanne Kersten Bianca Brosig Dirk Rohweder Martin Beyerbach Hermann Seifert | 2013 | Zeitschrift für Medizinische Physik2013，，： | 2 |
| 9 | Kontrastmittelsonografie bei B-Bild-morphologisch unklaren Leberraumforderungen – Diagnostische Treffsicherheit im klinischen Alltag (DEGUM-Multicenter – Studie)显示文摘 | D Strobel K Seitz W Blank A Schuler C Dietrich A Herbay M Friedrich-Rust G Kunze D Becker U Will W Kratzer F Albert C Pachmann K Dirks H Strunk C Greis T Bernatik | 2008 | Ultraschall in Med2008，，05： | 2 |
| 10 | Activity of phenylalanine ammonialyase, peroxidase and polyphenol oxidase in roots of banana(Musa acuminata AAA, cvs Grande Naine and Yangambi km5) before and after infection with Radophotus similes显示文摘 | Nathalie W Dirk D Rony S | 2006 | Nematology2006，8，2： | 1 |
| 11 | Tumor necrosis factor receptor-associated factor(TRAF)4 is a new binding partner for the p70S6 serine/threonine kinase显示文摘 | Fleckenstein D S Dirks W G Drexler H G | 2003 | Leuk Res2003，27，8： | 1 |
| 12 | The role of trust in organiza- tional settings 显示文摘 | Dirks K T Ferrin D L | 2001 | Organization Science2001，12，4： | 1 |
| 13 | High-resolution studies of rainfall on Norfolk Island Part II:interpolation of rainfall data 显示文摘 | Dirks K N Hay J E Stow C D | 1998 | Journal of Hydrology1998，208，3： | 1 |
| 14 | The role of trust in organization set-tings显示文摘 | Dirks K T Ferrin D L | 2001 | Organization Science2001，12，： | 1 |
| 15 | Experiments and modeling ofanisotropic aluminum extrusions under multi-axial loading-PartII: Ductile fracture显示文摘 | Luo M Matthieu D Dirk M | | International Journal of0，11，35： | 1 |
| 16 | The repair of trust: A dynamic bilateral perspective and multilevel conceptualization显示文摘 | Kim P H Dirks K T and Cooper C D | 2009 | Academy of Management Review2009，34，3： | 1 |
| 17 | The Use of Rewards to Increase and Decrease Trust:Mediating Processes and Differential Effects显示文摘 | Ferrin D L Dirks K T | 2003 | Organization Science2003，，： | 1 |
| 18 | A second target for the peptoid Tat/transactivation response element inhibitor CGP64222: inhibitor of human immunodeficiecy virus replication by blocking CXCR4-mediated virus entry显示文摘 | Dirk D Dominique S Myriam W | 2000 | Mol Pharmacol2000，57，1： | 1 |
| 19 | Extrinsic risk factors for compromised blood flow in the vertebral artery: anatomical observations of the transverse foramina from C3 to C7显示文摘 | Barbara Cagnie Erik Barbaix Elke Vinck Katharina D’Herde Dirk Cambier | 2005 | Surgical and Radiologic Anatomy2005，，4： | 1 |
| 20 | IQGAP1 protein specifies amplifying cancer cells in glioblastoma multiforme显示文摘 | BALENCI L CLARKE I D DIRKS P B | 2006 | Cancer Res2006，66，18： | 1 |
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