|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 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 | Macrophage secretory products induce an inflammatory phenotype in hepatocytes显示文摘AIM:To investigate the influence of macrophages on hepatocyte phenotype and function.METHODS:Macrophages were differentiated from THP-1 monocytes via phorbol myristate acetate stimulation and the effects of monocyte or macrophageconditioned medium on HepG2 mRNA and protein expression determined.The in vivo relevance of these findings was confirmed using liver biopsies from 147 patients with hepatitis C virus(HCV)infection.RESULTS:Conditioned media from macrophages,but not monocytes,induced a transient morphological change in hepatocytes associated with upregulation of vimentin(7.8±2.5-fold,P=0.045)and transforming growth factor(TGF)-β1(2.6±0.2-fold,P<0.001)and downregulation of epithelial cadherin(1.7±0.02-fold,P=0.017)mRNA expression.Microarray analysis revealed significant upregulation of lipocalin-2(17-fold,P <0.001)and pathways associated with inflammation,and substantial downregulation of pathways related to hepatocyte function.In patients with chronic HCV,realtime polymerase chain reaction and immunohistochemistry confirmed an increase in lipocalin-2 mRNA(F0 1.0 ±0.3,F1 2.2±0.2,F2 3.0±9.3,F3/4 4.0±0.8,P= 0.003)and protein expression(F1 1.0±0.5,F2 1.3± 0.4,F3/4 3.6±0.4,P=0.014)with increasing liver injury.High performance liquid chromatography-tandem mass spectrometry analysis identified elevated levels of matrix metalloproteinase(MMP)-9 in macrophageconditioned medium,and a chemical inhibitor of MMP-9 attenuated the change in morphology and mRNA expression of TGF-β1(2.9±0.2 vs 1.04±0.1,P<0.001) in macrophage-conditioned media treated HepG2 cells.In patients with chronic HCV infection,hepatic mRNA expression of CD163(F0 1.0±0.2,F1/2 2.8±0.3,F3/4 5.3±1.0,P=0.001)and MMP-9(F0 1.0±0.4,F1/2 2.8±0.3,F3/4 4.1±0.8,P=0.011)was significantly associated with increasing stage of fibrosis.CONCLUSION:Secreted macrophage products alter the phenotype and function of hepatocytes,with increased expression of inflammatory mediators,suggesting that hepatocytes actively participate in liver injury. | Michelle Melino Victoria L Gadd Gene V Walker Richard Skoien Helen D Barrie Dinesh Jothimani Leigh Horsfall Alun Jones Matthew J Sweet Gethin P Thomas Andrew D Clouston Julie R Jonsson Elizabeth E Powell | 2012 | World Journal of Gastroenterology2012，18，15： | 3 |
| 3 | Senescent human hepatocytes express a unique secretory phenotype and promote macrophage migration显示文摘AIM:To develop a model of stress-induced senescence to study the hepatocyte senescence associated secretory phenotype(SASP).METHODS:Hydrogen peroxide treatment was used to induce senescence in the human Hep G2 hepatocyte cell line.Senescence was confirmed by cytochemical staining for a panel of markers including Ki67,p21,heterochromatin protein 1β,and senescence-associated-β-galactosidase activity.Senescent hepatocytes were characterised by gene expression arrays and quantitative polymerase chain reaction(q PCR),and conditioned media was used in proteomic analyses,a human chemokine protein array,and cell migration assays to characterise the composition and function of the hepatocyte SASP.RESULTS:Senescent hepatocytes induced classical markers of senescence(p21,heterochromatin protein1β,and senescence-associated-β-galactosidase activity);and downregulated the proliferation marker,Ki67.Hepatocyte senescence induced a 4.6-fold increase in total secreted protein(P=0.06)without major alterations in the protein profile.Senescence-induced genes were identified by microarray(Benjamini Hochbergcorrected P<0.05);and,consistent with the increase in secreted protein,gene ontology analysis revealed a significant enrichment of secreted proteins among inducible genes.The hepatocyte SASP included characteristic factors such as interleukin(IL)-8 and IL-6,as well as novel components such as SAA4,IL-32and Fibrinogen,which were validated by q PCR and/or chemokine protein array.Senescent hepatocyteconditioned medium elicited migration of inflammatory(granulocyte-macrophage colony stimulating factor,GM-CSF-derived),but not non-inflammatory(CSF-1-derived)human macrophages(P=0.022),which could contribute to a pro-inflammatory microenvironment in vivo,or facilitate the clearance of senescent cells.CONCLUSION:Our novel model of hepatocyte senescence provides insights into mechanisms by which senescent hepatocytes may promote chronic liver disease pathogenesis. | Katharine M Irvine Richard Skoien Nilesh J Bokil Michelle Melino Gethin P Thomas Dorothy Loo Brian Gabrielli Michelle M Hill Matthew J Sweet Andrew D Clouston Elizabeth E Powell | 2014 | World Journal of Gastroenterology2014，20，47： | 2 |
| 4 | Effect of donor–recipient HLA matching at HLA A, B, C, and DRB1 on outcomes after umbilical-cord blood transplantation for leukaemia and myelodysplastic syndrome: a retrospective analysis显示文摘 | Mary Eapen John P Klein Guillermo F Sanz Stephen Spellman Annalisa Ruggeri Claudio Anasetti Maria Brown Richard E Champlin Joan Garcia-Lopez Gareth Hattersely Gesine Koegler Mary J Laughlin Gerard Michel Samir K Nabhan Franklin O Smith Mary M Horowitz Eli | 2011 | Lancet Oncology2011，，13： | 2 |
| 5 | Reducing probability of decision error using stochastic resonance 显示文摘 | S kay J Michels H Chen P Varshney | 2006 | IEEE Signal Processing letter2006，13，11： | 1 |
| 6 | Optimizing the receiver maneuvers for bearings-only tracking显示文摘 | Le Cadre J P Michel S L | 1999 | Elsevier Science on Automatic1999，35，5： | 1 |
| 7 | Multistep redirection by cross-beam power transfer of ultrahigh-power lasers in a plasrna显示文摘 | Moody J D Michel P Divol L | 2012 | Nature Phys2012，8，： | 1 |
| 8 | Chronic stress impairs rat growth and jejunal epithelial barrier function:role of mast cells 显示文摘 | SANTOS J MICHELLE B YANG P C | 2000 | Am J Physiol Gastrointest Liver Physiol2000，278，6： | 1 |
| 9 | Adaptive CFAR detection for clutter-edge heterogeneity using Bayesian inference 显示文摘 | Biao C Varshney P K and Michels J H | 2003 | IEEE Transactions on Aerospace and Electronic Systems2003，39，4： | 1 |
| 10 | Effect of ozonation on activated sludge solubilization and mineralization 显示文摘 | DELERIS S P ETIENNE MARC A J MICHEL R | 2000 | Ozone Sci Eng2000，22，： | 1 |
| 11 | Lower cardiac troponin T levels in patients undergoing cardiopulmonary bypass and receiving high-dose aprotinin therapy indicate reduction of perioperative myocardial damage显示文摘 | Michel J Heller W Wendel H P | 1995 | J Thorac Cardiovasc Surg1995，109，6： | 1 |
| 12 | Stress concentration in steel bridge orthotropic decks显示文摘 | Michele S P Ronaldo C B Aluision J R | 2005 | Journal of Constructional Steel Research2005，61，8： | 1 |
| 13 | Qualitativesimulation of the carbon starvation response in Escherichiacoli显示文摘 | Delphine R de Hidde J Michel P | 2006 | BioSystems2006，84，2： | 1 |
| 14 | Corneal arcus and hyperlipidemia: findings from an older population 显示文摘 | Chua BE Michell P Wang J J Rochtchina E | 2004 | Am J Ophthalm ol2004，137，2： | 1 |
| 15 | Complexation of porphyrin-appended guests by calixarene-appended cyclodextrins显示文摘 | Michels J J Fiammengo R Timmerman P | 2001 | J Inclu Pheno Macrocyclic Chem2001，41，124： | 1 |
| 16 | Evaluation of extraction and purification methods for obtaining PCR-amplifiable DNA from compost for microbial community analysis显示文摘 | LaMontagne M G Michel F C J Holden P A | 2002 | Journal of Microbiological Methods2002，49，3： | 1 |
| 17 | The thermal reactions of CH3 显示文摘 | Lim K P Michel J V | 1994 | Symp Int Combust Proc1994，25，： | 1 |
| 18 | The effect of height and frequency of mowing on the yield and composition of perennial ryegrass-white clover swards in the autumn to spring period显示文摘 | Fulkerson W J Michell P J | 1987 | Grass and Forage Science1987，42，： | 1 |
| 19 | Role of Pycnoporus coccineus laccase in the degradation of aromatic compounds in olive oil mill waste-water 显示文摘 | Atef J Francisco G Michel J P | 2005 | Enzyme and Microbial Technology2005，36，4： | 1 |
| 20 | Root distribution of two tree species under a heterogeneous nutrient environment显示文摘 | MOU P MICHELL R J JONES R H | 1997 | J Appl Ecol1997，34，： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员