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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 | Establishing proof of concept:Platelet-rich plasma and bone marrow aspirate concentrate may improve cartilage repair following surgical treatment for osteochondral lesions of the talus显示文摘Osteochondral lesions of the talus are common injuries in the athletic patient. They present a challenging clinical problem as cartilage has a poor potential for healing. Current surgical treatments consist of reparative(microfracture) or replacement(autologous osteochondral graft) strategies and demonstrate good clinical outcomes at the short and medium term follow-up. Radiological findings and second-look arthroscopy however, indicate possible poor cartilage repair with evidence of fibrous infill and fissuring of the regenerative tissue following microfracture. Longer-term follow-up echoes these findings as it demonstrates a decline in clinical outcome. The nature of the cartilage repair that occurs for an osteochondral graft to become integrated with the native surround tissue is also of concern. Studies have shown evidence of poor cartilage integration,with chondrocyte death at the periphery of the graft, possibly causing cyst formation due to synovial fluid ingress. Biological adjuncts, in the form of platelet-rich plasma(PRP) and bone marrow aspirate concentrate(BMAC), have been investigated with regard to their potential in improving cartilage repair in both in vitro and in vitro settings. The in vitro literature indicates that these biological adjuncts may increase chondrocyte proliferation as well as synthetic capability, while limiting the catabolic effects of an inflammatory joint environment. These findings have been extrapolated to in vitro animal models, with results showing that both PRP and BMAC improve cartilage repair. The basic science literature therefore establishes the proof of concept that biological adjuncts may improve cartilage repair when used in conjunction with reparative and replacement treatment strategies for osteochondral lesions of the talus. | Niall A Smyth Christopher D Murawski Amgad M Haleem Charles P Hannon Ian Savage-Elliott John G Kennedy | 2012 | World Journal of Orthopedics2012，3，7： | 8 |
| 3 | Platelet-rich plasma increases transforming growth factor-beta1 expression at graft-host interface following autologous osteochondral transplantation in a rabbit model显示文摘AIM: To explore the effect of platelet-rich plasma on protein expression patterns of transforming growth factor-beta1(TGF-β1) in cartilage following autologous osteochondral transplantation(AOT) in a rabbit knee cartilage defect model.METHODS: Twelve New Zealand white rabbits received bilateral AOT. In each rabbit, one knee was randomized to receive an autologous platelet rich plasma(PRP) injection and the contralateral knee received saline injection. Rabbits were euthanized at 3, 6 and 12 wk post-operatively. Articular cartilage sections were stained with TGF-β1 antibody. Histological regions of interest(ROI)(left, right and center of the autologous grafts interfaces) were evaluated using Meta Morph. Percentage of chondrocytes positive for TGF-β1 was then assessed.RESULTS: Percentage of chondrocytes positive for TGF-β1 was higher in PRP treated knees for selected ROIs(left; P = 0.03, center; P = 0.05) compared to control and was also higher in the PRP group at each post-operative time point(P = 6.6 × 10^(-4), 3.1 × 10^(-4) and 7.3 × 10^(-3) for 3, 6 and 12 wk, respectively). TGF-β1 expression was higher in chondrocytes of PRP-treated knees(36% ± 29% vs 15% ± 18%)(P = 1.8 × 10^(-6)) overall for each post-operative time point and ROI. CONCLUSION: Articular cartilage of rabbits treated with AOT and PRP exhibit increased TGF-β1 expression compared to those treated with AOT and saline. Our findings suggest that adjunctive PRP may increase TGF-β1 expression, which may play a role in the chondrogenic effect of PRP in vivo. | Lorraine A Boakye Keir A Ross John M Pinski Niall A Smyth Amgad M Haleem Charles P Hannon Lisa A Fortier John G Kennedy | 2015 | World Journal of Orthopedics2015，6，11： | 7 |
| 4 | miR 29b Expression is Associated with Disease-Free Survival in Patients with Ovarian Serous Carcinoma 显示文摘 | Flavin R Smyth P Barrett C | 2009 | Int J Gynecol Cancer2009，19，4： | 1 |
| 5 | An incremental retrieval mechanism for case-based electronic fault diagnosis 显示文摘 | Cunningham P Smyth B Bonzano A | 1998 | Knowledge-Based System1998，，： | 1 |
| 6 | A simple fast hybrid pattern-matching algorithm 显示文摘 | FRANEK F JENNINGS C G SMYTH P W F | 2007 | Journal of Discrete Algorithms2007，4，5： | 1 |
| 7 | Does iodine gas released from seaweed contribute to dietary iodine intake? 显示文摘 | SMYTH P P A BURNS R HUANG R J | 2011 | Environmental Geo- chemistry and Health2011，33，4： | 1 |
| 8 | Electricity consumption, em ployment and real income in Australia evidence from multiva- riate Granger causality tests显示文摘 | NARAYAN P K SMYTH R | 2005 | Energy Policy2005，33，9： | 1 |
| 9 | Intestinal transfer of choline in the rat and hamster显示文摘 | SANFORD P A SMYTH D H | 1971 | The Journal of Physiology1971，215，3： | 1 |
| 10 | Model-based clustering and visualization of navigation patterns on a Web site显示文摘 | Cadez I V Heekerman D Smyth P | 2003 | Knowledge Discovery and Data Mining2003，，： | 1 |
| 11 | Ligand Electronic Effects in Enantioselective Diethylzinc Additions显示文摘 | Smyth M | 2003 | Synlett2003，1，： | 1 |
| 12 | Ret/PTC chimeric transcripts in an Irish cohort of sporadic papillary thyroid carcinoma显示文摘 | Finn S P Smyth P O' Leary J | 2003 | J Clin Endocrinol Metab2003，88，： | 1 |
| 13 | Birkhead revised:petrological and geochemical studies of the Birkhead formation, Eromanga Basin显示文摘 | Smyth M Cook A C Philp R P | 1984 | APEA1984，24，1： | 1 |
| 14 | Glucocorticoid pretreatment induces eytokine over expression and nuclear facto-β activation in macrophages显示文摘 | Smyth G P Stapleton P P Freeman T A | 2004 | J Surg Res2004，11，： | 1 |
| 15 | A Simple Fast Hybrid Pattern-matching Algorithm显示文摘 | Franek F Jennings C G Smyth P W F | 2007 | Journal of Discrete Algorithms2007，4，5： | 1 |
| 16 | Temperature-regulated expression of the tac/lacl system for overproduction of a fungal xylanase in Escherichia coli 显示文摘 | Xue G P Johnson D J Smyth D J | 1996 | Appl Microbiol Biotechnol1996，45，： | 1 |
| 17 | miR-29b expression is associated with disease-free survival in patient with ovarian serous carcinoma显示文摘 | Flavin R Smyth P Barrett C | 2009 | Int J Gynecol Cancer2009，19，4： | 1 |
| 18 | The KDD process for extracting useful knowledge from volume of Data显示文摘 | Fayyad U Piatetsky-Shapiro G Smyth P | 1996 | Communication of the ACM1996，39，11： | 1 |
| 19 | The KDD process of extracting useful knowledge from volumes of data显示文摘 | Fayyad U Piatetsky-Shapiro G Smyth P | 1996 | Communications of the ACM1996，39，11： | 1 |
| 20 | A panel cointegration analysis of the demand for oil in the Middle East 显示文摘 | Narayan P K Smyth R | 2007 | Energy Policy2007，35，： | 1 |
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