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Expression of TRAIL and TRAIL receptors in normal and malignant tissues

Cell Research 2005年第6期15卷 430-438页

作者： Raymond A DANIELS,Helen TURLEY,Fiona C KIMBERLEY,Juthathip MONGKOLSAPAYA,Paul CH’EN,Francesco PEZZELLA,Gavin R SCREATON Human Immunology Unit Weatherall Institute of Molecular Medicine University of Oxford John Radcliffe Hospital Oxford OX3 9DS UK Nuffield Department of Clinical Laboratory Sciences University of Oxford John Radcliffe Hospital Oxford OX3 9DS UK Hammersmith Hospital du cane road London W12 0NN UK Hammersmith Hospital du cane road London W12 0NN UK Human Immunology Unit Weatherall Institute of Molecular Medicine University of Oxford John Radcliffe Hospital Oxford OX3 9DS UK Nuffield Department of Clinical Laboratory Sciences University of Oxford John Radcliffe Hospital Oxford OX3 9DS UK Hammersmith Hospital du cane road London W12 0NN UK

TRAIL, tumor necrosis factor-related apoptosis-inducing ligand, is a member of the TNF family of *** cells were initially found to have increased sensitivity to TRAIL compared with normal cells, raising hopes thatTRAIL would prove useful as an anti-tumor agent. The production of reliable monoclonal antibodies against TRAIL andits receptors that can stain fixed specimens will allow a thorough analysis of their expression on normal and malignanttissues. Here we report the generation of monoclonal antibodies against TRAIL and its four membrane-bound receptors(TR1–4), which have been used to stain a range of normal and malignant cells, as routinely fixed specimens. Low levelsof TRAIL expression were found to be limited mostly to smooth muscle in lung and spleen as well as glial cells in thecerebellum and follicular cells in the thyroid. Expression of the TRAIL decoy receptors (TR3 and 4) was not aswidespread as indicated by Northern blotting, suggesting that they may be less important for the control of TRAILcytotoxicity than previously thought. TR1 and TR2 expression increases significantly in a number of malignant tissues,but in some common malignancies their expression was low, or patchy, which may limit the therapeutic role of *** together, we have a panel of monoclonal antibodies that will allow a better assessment of the normal role ofTRAIL and allow assessment of biopsy material, possibly allowing the identification of tumors that may be amenable toTRAIL therapy.

关键词： apoptosis immunohistochemistry monoclonal antibodies tumor markers.

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Following a TRAIL: Update on a ligand and its five receptors

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Cell Research 2004年第5期14卷 359-372页

作者： Fiona C. KIMBERLEY,Gavin R. SCREATON Weatherall Institute of Molecular Medicine Human Immunology Unit John Radcliffe Hospital Oxford OX3 9DS UK Department of Medicine Hammersmith Hospital Imperial College du cane road London W12 0NN UK.

Identification of tumour necrosis factor apoptosis inducing ligand (TRAIL), a TNF family ligand, sparked a torrent of research, following an initial observation that it could kill tumour cells, but spare normal cells. Almost a decade after its discovery, and with five known receptors, the true physiological role of TRAIL is still debated and its anti-tumorigenic properties limited by potential toxicity. This review takes a comprehensive look at the story of this enigmatic ligand, addressing its remaining potential as a therapeutic and providing an overview of the TRAIL receptors themselves.

关键词： TRAIL apoptosis cancer.

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Diagnosis of hepatocellular carcinoma

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World Journal of Gastroenterology 2009年第11期15卷 1301-1314页

作者： Asmaa I Gomaa Shahid A Khan Edward LS Leen Imam Waked Simon D Taylor-Robinson Department of Hepatology and Gastroenterology Division of Medicine Imperial College London St Mary's Hospital Campus South Wharf Road London W2 1NY United Kingdom National Liver Institute Menoufi ya University Shebeen ElKom 32111 Egypt Imaging Sciences Department MRC Clinical Sciences Centre Imperial College London Hammersmith Hospital Campus Du Cane Road London W12 0HS United Kingdom

Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the diagnosis of HCC, including serum markers, radiological techniques and histological evaluation, and summarises international guidelines for the diagnostic approach to HCC.

关键词：原发性肝癌诊断组织学评价肝细胞癌血清标志辐射技术 HCC 发病率

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In situ hybridization of neuropeptide Y gene expression in the endothelial cells of human umbilical blood vessels

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Chinese Science Bulletin 1995年第12期40卷 1022-1027页

作者：蔡文琴 G. Terenghi P. Bodin G. Burnstock J. Polak Department of Histology and Embryology The 3rd Military Medical College Chongqing 630038 China Department of Histochemistry Royal postgraduate Medical SchoolHammersmith HospitalDu Cane RoadLondon W12 ONNU.K Department of Anatomy and Developmental Biology and Centre of Neuroscience University College LondonGower streetLondon WCIE 6BTU.K

In recent years, the endothelial cell has become the popular subject of many scientificresearch fields such as cardiovascular and cancer pathology. The results reported up to nowindicate that the endothelial cell has the complex funtion in synthesis and metabolism, andtherefore plays an important role in the regulation of vascular function. Burnstock’s labfirst observed that many kinds of vasoactive substances are localized in the endothelial

关键词： neuropeptide Y in situ hybridization endothelial cells human umbilical blood vessels.

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An automated multiwell plate reading flim microscope for live cell autofluorescence lifetime assays

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Journal of Innovative Optical Health Sciences 2014年第5期7卷 99-113页

作者： Douglas J.Kelly Sean C.Warren Sunil Kumar Joao L.Lagarto Benjamin T.Dyer Anca Margineanu Eric W.-F.Lam Chris dunsby Paul M.W.French Photonics Group Department of PhysicsImperial College London South Kensington CampusLondonSW72AZUK Institute of Chemical Biology Department of Chemistry Imperial College LondonSouth Kensington Campus LondonSWT 2AZUK National Heart&Lung Institute Imperial Centre for Eaperimental&Translational Medicine du cane road LondonW12 ONNUK Department of Surgery and Cancer Imperial Cllege London Du Cane RoadLondonW12 ONNUK Centre for Histopathology Imperial College London Du Cane RoadLondonW120NNUK

Fluorescence lifetime imaging(FLIM)is increasingly used to read out cellular autofluorescenceoriginating from the coenzyme NADH in the context of investigating cell metabolic *** here an automated multiwell plate reading FLIM microscope optimized for UV illumi-nation with the goal of extending high content fluorescence lifetime asays to readouts ofmetabolism,We demonstrate its application to automated cellular autofluorescence lifetime imaging and discuss the key practical issues associated with its *** particular,weillustrate its capability to read out the NADH-lifetime response of cells to metabolic modulators,thereby illustrating the potential of the instrument for cytotoxicity studies,assays for drugdiscovery and stratified medicine.

关键词： High content analysis FLIM NADH metabolism cisplatin.

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Complement activation by phospholipids: the interplay of factor H and C1q

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Protein & Cell 2010年第11期1卷 1033-1049页

作者： Lee Aun Tan Bingbin Yu Francis CJ Sim Uday Kishore Robert B Sim MRC Immunochemistry Unit Department of BiochemistryUniversity of OxfordSouth Parks RdOxford OX13QUUK Department of Pharmacology University of OxfordMansfield RoadOxford OX13QTUK Centre for Infection Immunity and Disease MechanismsBiosciencesSchool of Health Sciences and Social CareBrunel UniversityUxbridge UB83PH West LondonUK Present address Department of Immunology Faculty of MedicineImperial College LondonHammersmith HospitalDu Cane RoadLondon W120NNUK Present address School of Life Sciences and Engineering Biology BuildingTsinghua UniversityBeijing 100084China

Complement proteins in blood recognize charged *** anionic phospholipid(aPL)cardiolipin binds both complement proteins C1q and factor H.C1q is an activator of the complement classical pathway,while factor H is an inhibitor of the alternative *** examine opposing effects of C1q and factor H on complement activation by aPL,we surveyed C1q and factor H binding,and complement activation by aPL,either coated on microtitre plates or in *** C1q and factor H bound to all aPL tested,and competed directly with each other for *** the aPL activated the complement classical pathway,but negligibly the alternative pathway,consistent with accepted roles of C1q and factor ***,in this system,factor H,by competing directly with C1q for binding to aPL,acts as a direct regulator of the complement classical *** regulatory mechanism is distinct from its action on the alternative *** of classical pathway activation by factor H was confirmed by measuring C4 activation by aPL in human sera in which the C1q:factor H molar ratio was adjusted over a wide *** factor H,which is regarded as a down-regulator only of the alternative pathway,has a distinct role in downregulating activation of the classical complement pathway by aPL.A factor H homologue,β2-glycoprotein-1,also strongly inhibits C1q binding to *** globular domains of C1q A,B and C chains bound aPL similarly to native C1q,confirming that C1q binds aPL via its globular heads.

关键词： complement regulation classical pathway C1q factor H anionic phospholipid

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伦琴对电磁理论的重要贡献

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物理 2007年第4期36卷 325-329页

作者： Peter Dawson 游胤涛马世红 Department of Radiology Hammersmith Hospital/RPMSDu Cane RoadLondon W120NNUK 复旦大学物理学系上海200433

提到伦琴,人们往往想到的是他对X射线的发现,而对他在电磁理论方面的重要贡献则较少提及.文章详细叙述了伦琴为论证“位移电流”存在而做的实验,此实验曾被誉为是19世纪最重要的物理实验之一,在当时广受赞誉,但今天却被人们渐渐遗忘了.... 详细信息

提到伦琴,人们往往想到的是他对X射线的发现,而对他在电磁理论方面的重要贡献则较少提及.文章详细叙述了伦琴为论证“位移电流”存在而做的实验,此实验曾被誉为是19世纪最重要的物理实验之一,在当时广受赞誉,但今天却被人们渐渐遗忘了.希望该文能够使人们对伦琴为构建19世纪物理学宏伟大厦而取得成就的重要性有更深入的认识.

关键词：伦琴位移电流麦克斯韦电磁理论

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Teasing apart the multiple roles of Shp2(Ptpn11)in spermatogenesis

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Asian Journal of Andrology 2020年第1期22卷 122-122页

作者： Geoffrey J Maher Anne Goriely Clinical Genetics Group MRC Weatherall Institute of Molecular MedicineUniversity of OxfordOxford 0X39DSUK ICTEM Building Hammersmith CampusImperial College LondonDu Cane RoadLondonW12 ONNUK

Dear Editor,Varicocele is a common cause of male infertility,but in the course of a diagnostic infertility workup,other underlying problems are often *** to two-thirds of patients with nonidiopathic male infertility h... 详细信息

关键词： infertility Shp2 easing

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Interactions of complement proteins C1q and factor H with lipid A and Escherichia coli:further evidence that factor H regulates the classical complement pathway

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Protein & Cell 2011年第4期2卷 320-332页

作者： Lee Aun Tan Andrew C.Yang Uday Kishore Robert B.Sim Medical Research Council Immunochemistry Unit Department of BiochemistryUniversity of OxfordSouth Parks RoadOxford OX13QUUK Present address:Department of Immunology Faculty of MedicineImperial College LondonHammersmith HospitalDu Cane RoadLondon W120NNUK St Peter’s College New Inn Hall St.Oxford OX12DLUK Present address:SUNY Downstate College of Medicine 450 Clarkson Avenue BrooklynNY 11203USA Weatherall Institute of Molecular Medicine John Radcliffe HospitalUniversity of OxfordHeadingtonOxford OX39DSUK Present address:Center for Infection Immunity and Disease MechanismsBiosciencesSchool of Health Sciences and Social CareBrunel UniversityUxbridge UB83PH West LondonUK Present address:Department of Pharmacology University of OxfordMansfield RoadOxford OX13QTUK

Proteins of the complement system are known to interact with many charged *** recently characterized binding of C1q and factor H to immobilized and liposomal anionic *** H inhibited C1q binding to anionic phospholipids,suggesting a role for factor H in regulating activation of the complement classical pathway by anionic *** extend this finding,we examined interactions of C1q and factor H with lipid A,a well-characterized activator of the classical *** report that C1q and factor H both bind to immobilized lipid A,lipid A liposomes and intact Escherichia coli *** H competes with C1q for binding to these ***,increasing the factor H:C1q molar ratio in serum diminished C4b fixation,indicating that factor H diminishes classical pathway *** recombinant forms of the Cterminal,globular heads of C1q A,B and C chains bound to lipid A and *** in a manner qualitatively similar to native C1q,confirming that C1q interacts with these targets via its globular head *** observations reinforce our proposal that factor H has an additional complement regulatory role of down-regulating classical pathway activation in response to certain *** is distinct from its role as an alternative pathway *** suggest that under physiological conditions,factor H may serve as a downregulator of bacterially-driven inflammatory responses,thereby finetuning and balancing the inflammatory response in infections with Gram-negative bacteria.

关键词： complement lipid A bacteria factor H C1q

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Non-invasive means of measuring hepatic fat content

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World Journal of Gastroenterology 2008年第22期14卷 3476-3483页

作者： Sanjeev R Mehta E Louise Thomas Jimmy D Bell Desmond G Johnston Simon D Taylor-Robinson Division of Medicine Imperial College London St Mary's Campus Praed Street London W2 1NY United Kingdom Imaging Sciences Depart-ment Division of Clinical Sciences Imperial College London Hammersmith Campus Du Cane Road London W12 OHS United Kingdom

Hepatic steatosis affects 20% to 30% of the general adult population in the western world. Currently, the technique of choice for determining hepatic fat deposition and the stage of fibrosis is liver biopsy. However, it is an invasive procedure and its use is limited, particularly in children. It may also be subject to sampling error. Non-invasive techniques such as ultrasound, computerised tomography (CT), magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H MRS) can detect hepatic steatosis, but currently cannot distinguish between simple steatosis and steatohepatitis, or stage the degree of fibrosis accurately. Ultrasound is widely used to detect hepatic steatosis, but its sensitivity is reduced in the morbidly obese and also in those with small amounts of fatty infiltration. It has been used to grade hepatic fat content, but this is subjective. CT can detect hepatic steatosis, but exposes subjects to ionising radiation, thus limiting its use in longitudinal studies and in children. Recently, magnetic resonance (MR) techniques using chemical shift imaging have provided a quantitative assessment of the degree of hepatic fatty infiltration, which correlates well with liver biopsy results in the same patients. Similarly, in vivo 1H MRS is a fast, safe, non-invasive method forthe quantification of intrahepatocellular lipid (IHCL) levels. Both techniques will be useful tools in future longitudinal clinical studies, either in examining the natural history of conditions causing hepatic steatosis (e.g. non-alcoholic fatty liver disease), or in testing new treatments for these conditions.

关键词：脂肪纤维异常肥胖脂肪肝胰岛素耐药性超声检查

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