Blizard Institute Research Articles

Fibrino(Geno)Lysis: The New Kid in Town for Trauma Care

Centre for Trauma Sciences, The Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London

British Society for Investigative Dermatology Annual Meeting 2018 26-28 March 2018 Blizard Institute, Barts and The London School of Medicine and Dentistry

British Society for Investigative Dermatology Annual Meeting 2018 26-28 March 2018 Blizard Institute, Barts and The London School of Medicine and Dentistry

Matrix metalloproteinase protein inhibitors: highlighting a new beginning for metalloproteinases in medicine

Matrix metalloproteinase protein inhibitors: highlighting a new beginning for metalloproteinases in medicine Barbara J Boucher The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UKThe review by Mohan et al1 is interesting because increased activity of various matrix metalloproteinases (MMPs), increasing the severity of tissue damage, is found in many different disease processes. To reduce tissue-damaging overactivity of these tissue remodeling enzymes, one can reduce MMP secretion, or increase the secretion of tissue inhibitors of MMPs (TIMPs); developing therapeutic agents, or boosting natural tissue MMP inhibitors, is therefore an important and worthwhile project. However, this review does not mention vitamin D which is essential for bone health and is known to regulate bone growth through MMP modulation,2 and increasingly reported as suppressing the overactivity of certain MMPs, especially MMP-2 and MMP-9, in many pathological disorders (although vitamin A can also modulate some MMPs). View the original paper by Mohan and colleagues.

Gavin Giovannoni on why time matters in multiple sclerosis.

Gavin Giovannoni was appointed in November 2006 to the Chair of Neurology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London and the Department of Neurology, Barts and The London NHS Trust (all UK). In September 2008, he took over as the Neuroscience and Trauma Centre Lead in the Blizard Institute. Gavin did his undergraduate medical training at the University of the Witwatersrand, South Africa, where he graduated cum laude in 1987. He moved to the Institute of Neurology, University College London, Queen Square, London (UK) in 1993 after completing his specialist training in neurology in South Africa. Following 3 years as a clinical research fellow, under Professor Ed Thompson, and 2 years as the Scarfe Lecturer, working for Professor W. Ian McDonald, Gavin was awarded a PhD in immunology from the University of London (UK) in 1998. That year, he was also appointed as a Clinical Senior Lecturer, Royal Free and University College Medical School (UK), and in 1999 he moved back to Institute of Neurology, Queen Square (UK). He was promoted to Reader in Neuroimmunology in 2004. His clinical interests are multiple sclerosis (MS) and other inflammatory disorders of the central nervous system. Gavin is particularly interested in clinical issues related to optimizing disease-modifying therapies in MS. His current research is focused on Epstein–Barr virus as a possible cause of MS, defining the ‘MS endophenotype’, MS-related neurodegeneration, MS biomarker discovery, MS clinical outcomes and immune tolerance strategies. His team focuses on translational research and therefore has an active clinical trial program.

PI3K-C2B plays a key role in the activation and the proliferation of t lymphocytes: Impact on vascular diseases

PI3K-C2B plays a key role in the activation and the proliferation of t lymphocytes: Impact on vascular diseases

SP-017 PRODUCTS SITUATION OF THE BIOSIMILARS IN TURKEY AND IN THE WORLD

SP-017 – Table 1. Registered biosimiliars in Turkey (2009–2013) Product name Active substance Production site Reg. year, licensee LEUCOSTIM FILGRASTIM SOUTH KOREA (DONG-A) 2009, DEMMEDIKAL VE ECZA DEPOSU SAN VE TIC. LTD. STI. EPOBEL EPOETIN ZETA GERMANY (STADA) 2009, NOBEL ILAC PAZARLAMA VE SAN. LTD. STI. EPORON EPOETIN ALFA SOUTH KOREA (DONG-A) 2011, DEMMEDIKAL VE ECZA DEPOSU SAN VE TIC. LTD. STI. OMNITROPE SOMATROPIN AUSTRIA (SANDOZ) 2011, SANDOZ ILAC SAN. VE TIC. A.S. OKSAPAR ENOXAPARIN SODIUM TURKEY 2012, KOCAK FARMA ILAC VE KIMYA SAN. A.S. CLOTINAB ABCIXIMAB SOUTH KOREA (DONG-A) 2012, DEMMEDIKAL VE ECZA DEPOSU SAN VE TIC. LTD. STI. EPOPLUS EPOETIN ALFA CUBA 2013 HASBIOTECH ILAC SAN. VE TIC. A.S. ENOX ENOXAPARIN SODIUM TURKEY 2013, ATABAY KIMYA SAN. VE TIC. A.S. DROPOETIN EPOETIN ALFA TURKEY 2013, DROGSAN ILACLARI SAN. VE TIC. A.S. within 5 years of diagnosis. Thrombosis and CKD are leading causes of death in PNH: 40–67% of death are due to venous and arterial thrombosis, 64% of patients have CKD, which causes mortality in 8–18% of those patients. aHUS is a severe life-threatening disorder of uncontrolled complement activation resulting in thrombotic microangiopathy (TMA) in children and adults. TMA has a devastating impact on kidneys and other vital organs, 60% pf patients require dialysis, undergo kidney transplant or die within 1 year of diagnosis. The humanized monoclonal antibody eculizumab inhibits the terminal complement cascade by binding to human complement protein C5, inhibiting the formation of proinflammatory, prothrombotic C5a and C5b, with subsequent inhibition of assembly of the membrane attack complex. Multinational clinical studies in patients with PNH and aHUS demonstrated that eculisumab induces a rapid and clinically significant reduction in intravascular hemolysis and thrombotic events in PNH patients and TMA control and improvement of renal function in patients with aHUS. The data from Russian PNH and aHUS Registry present the demographic and clinical characteristics, incidence of complications and experience of patient treatment. Russian cohort in PNH Registry counts app 500 pts, aHUS app 40 pts. Recent achievements in diagnostic and treatment of PNH and aHUS made us responsible for the National guidelines development. There are several disease models described in the PNH guidelines where Russian experts recommend to use pathogenetic treatment. aHUS diagnostic and treatment experience also resulted in the Experts position paper and requires further consolidated efforts to prepare useful document for the medical community. SP-020 DIAGNOSIS, CLINICAL MANAGEMENT AND STEWARDSHIP FOR INVASIVE FUNGAL DISEASE IN HAEMATO-ONCOLOGY S.G. Agrawal. Department of Haemato-Oncology, Stem Cell Laboratory and Immunophenotyping Sections, Barts Health NHS Trust, London; Pathology Group, Blizard Institute, Queen Mary University of London, UK Antimicrobial stewardship has become a headline priority for governments and for international bodies, such as WHO. Antifungal stewardship is a highly specialized subset of this approach. I will discuss stewardship in the context of Haemato-Oncology as a further tool to ensure optimal patient management and resource utilization, over and beyond the development of care pathways for invasive fungal disease (IFD). A successful pathway requires “ownership” of the pathway by the clinical team looking after the patient, radiology, microbiology, infectious disease and respiratory physicians. . . My presentation will focus on the current debate on management strategies for IFD in Haemato-Oncology and the changes in our management algorithms over the last 12 years at St Bartholomew’s Hospital, London. I will present our updated diagnostic strategy, which uses three tests directed at Aspergillus detection – PCR, galactomannan and the LFD assay. The introduction of this triple testing strategy – “TRIADx” – will support the antifungal stewardship team, which will work closely with the Haemato-Oncology physicians and guide all aspects of IFD management.

SP-019 PATHOGENETIC TREATMENT OF PNH AND AHUS: RUSSIAN EXPERIENCE

SP-017 – Table 1. Registered biosimiliars in Turkey (2009–2013) Product name Active substance Production site Reg. year, licensee LEUCOSTIM FILGRASTIM SOUTH KOREA (DONG-A) 2009, DEMMEDIKAL VE ECZA DEPOSU SAN VE TIC. LTD. STI. EPOBEL EPOETIN ZETA GERMANY (STADA) 2009, NOBEL ILAC PAZARLAMA VE SAN. LTD. STI. EPORON EPOETIN ALFA SOUTH KOREA (DONG-A) 2011, DEMMEDIKAL VE ECZA DEPOSU SAN VE TIC. LTD. STI. OMNITROPE SOMATROPIN AUSTRIA (SANDOZ) 2011, SANDOZ ILAC SAN. VE TIC. A.S. OKSAPAR ENOXAPARIN SODIUM TURKEY 2012, KOCAK FARMA ILAC VE KIMYA SAN. A.S. CLOTINAB ABCIXIMAB SOUTH KOREA (DONG-A) 2012, DEMMEDIKAL VE ECZA DEPOSU SAN VE TIC. LTD. STI. EPOPLUS EPOETIN ALFA CUBA 2013 HASBIOTECH ILAC SAN. VE TIC. A.S. ENOX ENOXAPARIN SODIUM TURKEY 2013, ATABAY KIMYA SAN. VE TIC. A.S. DROPOETIN EPOETIN ALFA TURKEY 2013, DROGSAN ILACLARI SAN. VE TIC. A.S. within 5 years of diagnosis. Thrombosis and CKD are leading causes of death in PNH: 40–67% of death are due to venous and arterial thrombosis, 64% of patients have CKD, which causes mortality in 8–18% of those patients. aHUS is a severe life-threatening disorder of uncontrolled complement activation resulting in thrombotic microangiopathy (TMA) in children and adults. TMA has a devastating impact on kidneys and other vital organs, 60% pf patients require dialysis, undergo kidney transplant or die within 1 year of diagnosis. The humanized monoclonal antibody eculizumab inhibits the terminal complement cascade by binding to human complement protein C5, inhibiting the formation of proinflammatory, prothrombotic C5a and C5b, with subsequent inhibition of assembly of the membrane attack complex. Multinational clinical studies in patients with PNH and aHUS demonstrated that eculisumab induces a rapid and clinically significant reduction in intravascular hemolysis and thrombotic events in PNH patients and TMA control and improvement of renal function in patients with aHUS. The data from Russian PNH and aHUS Registry present the demographic and clinical characteristics, incidence of complications and experience of patient treatment. Russian cohort in PNH Registry counts app 500 pts, aHUS app 40 pts. Recent achievements in diagnostic and treatment of PNH and aHUS made us responsible for the National guidelines development. There are several disease models described in the PNH guidelines where Russian experts recommend to use pathogenetic treatment. aHUS diagnostic and treatment experience also resulted in the Experts position paper and requires further consolidated efforts to prepare useful document for the medical community. SP-020 DIAGNOSIS, CLINICAL MANAGEMENT AND STEWARDSHIP FOR INVASIVE FUNGAL DISEASE IN HAEMATO-ONCOLOGY S.G. Agrawal. Department of Haemato-Oncology, Stem Cell Laboratory and Immunophenotyping Sections, Barts Health NHS Trust, London; Pathology Group, Blizard Institute, Queen Mary University of London, UK Antimicrobial stewardship has become a headline priority for governments and for international bodies, such as WHO. Antifungal stewardship is a highly specialized subset of this approach. I will discuss stewardship in the context of Haemato-Oncology as a further tool to ensure optimal patient management and resource utilization, over and beyond the development of care pathways for invasive fungal disease (IFD). A successful pathway requires “ownership” of the pathway by the clinical team looking after the patient, radiology, microbiology, infectious disease and respiratory physicians. . . My presentation will focus on the current debate on management strategies for IFD in Haemato-Oncology and the changes in our management algorithms over the last 12 years at St Bartholomew’s Hospital, London. I will present our updated diagnostic strategy, which uses three tests directed at Aspergillus detection – PCR, galactomannan and the LFD assay. The introduction of this triple testing strategy – “TRIADx” – will support the antifungal stewardship team, which will work closely with the Haemato-Oncology physicians and guide all aspects of IFD management.

The Relationship Between Symptom Improvement and Gastric Emptying in the Treatment of Gastroparesis: Remember the Pharmacology

1 Neurogastroenterology Group, National Centre for Bowel Research and Surgical Innovation, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK Correspondence: G.J. Sanger, DSc, Neurogastroenterology Group, Barts and The London School of Medicine and Dentistry, National Centre for Bowel Research and Surgical Innovation, Blizard Institute, 1st Floor, Abernethy Building, 2 Newark Street, London E1 2AT, UK. E-mail: [email protected]

Neuroradiological efficacy of oral BG-12 for relapsing–/INS;remitting multiple sclerosis (RRMS): Integrated analysis of the Phase 3 DEFINE and CONFIRM studies

Neuroradiological efficacy of oral BG-12 for relapsing–/INS;remitting multiple sclerosis (RRMS): Integrated analysis of the Phase 3 DEFINE and CONFIRM studies

Hair follicle culture—a historical perspective

1. Michael P. Philpott (m.p.philpott{at}qmul.ac.uk) 1. DPhil Centre for Cutaneous Research Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London UK In order to understand the mechanisms involved in the regulation of hair follicle

New targets and developments in lipoproteins control

New targets and developments in lipoproteins control Giuseppe Danilo Norata1–31Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Italy; 2Center for the Study of Atherosclerosis, Società Italiana Studio Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy; 3The Blizard Institute, Centre for Diabetes, Barts and The London School of Medicine and Dentistry, Queen Mary University, London, UKAbstract: Statins provide a very effective approach in reducing plasma cholesterol levels and cardiovascular risk. However, the proportion of patients who fail to achieve desirable plasma lipid levels ranges from 16%–53%, worldwide. This percentage reaches up to 80% in patients with familial hypercholesterolemia. Additionally, many patients are unable to tolerate statins, particularly at the highest approved dose level. New treatments that aggressively reduce lipid levels in patients with severe hypercholesterolemia, or those unable to reach their lipid targets, are therefore required. The most promising approaches in this context, such as inhibitors of the synthesis of apolipoprotein B (apoB) containing lipoproteins (apoB silencing or microsomal triglyceride transfer protein [MTP] inhibition) or proprotein convertase subtilisin/kexin type 9 (PCSK9) blockers, all decrease low-density lipoprotein (LDL) extensively. Increasing low levels of high-density lipoprotein (HDL) cholesterol via cholesteryl ester transfer protein inhibitors or apolipoprotein A-1 (ApoA-1) inducers and improving their quality with HDL or ApoA-1 mimetics represent also important options. Drugs affecting HDL, however, may not be all alike and require adequate scrutiny of the mechanisms involved. Until we have a better understanding of these issues, further LDL lowering in high-risk patients represents the soundest approach.Keywords: apolipoproteins, lipids, lipoprotein classes, hypercholesterolemia, synthesis, LDL lowering

Current insights into protease dynamics in human epithelial disease and barrier function

The fundamental importance of proteolytic enzymes to the biology of all living organisms is manifestly demonstrated by genomic analyses which demonstrate that genes encoding proteases and their inhibitors account for over 2 % of the coding sequences of most genomes sequenced to date. For example, over 500 protease genes have been annotated in the human genome. This extraordinary diversity reflects the wide range of biological functions performed by this family of enzymes: in addition to relatively non-specific degradative functions, characterized for example by digestive enzymes of the intestine, proteases also perform the selective and limited cleavage of a myriad of protein substrates which defines their subsequent biological functions and properties. In so doing, protease-dependent peptide bond hydrolysis ranks among the most significant of all posttranslational modification systems and underpins the processes of development, tissue homeostasis, turnover and remodelling, immune protection and healing. Given their central role in health, it is unsurprising that imbalances in protease activity are also intimately associated with both inherited and acquired human conditions. Proteases are generally classified on the basis of their mechanism of peptide bond cleavage. Four major families are well known. In the case of serine and cysteine enzymes, the hydroxyl and thiol residues respectively act as the nucleophilic groups in catalyzing hydrolytic peptide bond cleavage. Metalloenzymes, utilize a metal ion, frequently Zn, at their active site to activate a molecule of water to act as the nucleophile attack group. In aspartyl, sometimes referred to as acidic, proteases a similar mechanism of action to the metallo-enzymes is proposed in which a molecule of water is co-ordinated in the active site between two conserved aspartic acid residues, one of which causes activation of the water by removal of a proton and formation of the nucleophilic group required for peptide bond cleavage. In addition to these well known major catalytic classes, a number of additional mechanisms of peptide bond cleavage are now recognized leading to an expanded classification system which includes three additional classes. A subset of acidic proteases was originally identified based on their resistance to pepstatin, a broad spectrum inhibitor of proteases active at acidic pH. The unusual active sites of this pepstatin-insensitive subset proved difficult to characterise, but it is now recognized that some members of the subset were actually misclassified serine proteases, but with an acidic pH optimum, whilst the remainder represented a new class of protease containing glutamic acid/glutamine in their active site rather than aspartic acid. A further catalytic type of protease was identified following the elucidation of the crystallographic structure of the yeast proteasome which demonstrated the presence of an N-terminal threonine at the reactive centre fulfilling a similar nucleophilic role to the serine residue in the active sites of serine proteases. Once again this helped explain an inhibitor resistance phenomenon in that the proteasome was well known to be insensitive to inhibition by a wide range of standard protease inhibitors. The final and most recent addition to the list of classes is unusual in that members of this group are not proteases at all: they do not achieve peptide bond through hydrolysis, but instead act through the specific and unusual chemistry of asparagine. An asparagine residue at the active site is able to act as a nucleophile and cause autolytic cleavage of the peptide chain. In this instance the asparagine residue is destroyed and therefore the active site functions only once. The reader is referred to the MEROPS database (http://merops.sanger.ac.uk) which provides an excellent on M. A. Curtis :D. P. Kelsell (*) Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Whitechapel, London E1 2AT, UK e-mail: d.p.kelsell@qmul.ac.uk

Early growth response gene 2 and 3 are essential for the regulation of tumour suppressor genes, Ikaros, Aiolos and FOXO3.

Event Abstract Back to Event Early growth response gene 2 and 3 are essential for the regulation of tumour suppressor genes, Ikaros, Aiolos and FOXO3. Punamdip K. Bhullar1*, Tizong Miao2, Alistair L. Symonds2, Emma Ghaffari1, Su-Ling Li1 and Ping Wang2 1 Brunel University, Bioscience, United Kingdom 2 Barts and London School of Medicine and Dentistry, Blizard Institute, United Kingdom Non-Hodgkin lymphoma is the fifth most common cancer in the UK, accounting for 4% of all new cases and is associated with inflammatory autoimmunity. The understanding of lymphomagenesis still remains a challenge. We have discovered that early growth response gene (Egr) -2 and -3 are essential for the control of inflammatory responses of lymphocytes and also involve in the regulation of antigen-mediated proliferation. In addition to the control of inflammatory responses, here we report a novel role of Egr- 2 and/or -3, in controlling the development of lymphoma. The deletion of Egr-2 and Egr-3 in lymphocytes results in spontaneous B or T lymphoma. Despite poor responses to antigen stimulation, Egr-2 and -3 deficient B and T cells are resistant to apoptosis and survival longer in vitro in the absence of overt stimulation. We have discovered that Egr-2 and/or -3 directly bind to the promoter regions on Ikaros, Aiolos and FOXO3. The deletion of Egr-2 and -3 down regulates Ikaros, Aiolos and FOXO3 in T and B cells. The impaired expression associates with proliferative disorder and the development of T and B cell lymphoma. Thus, Egr-2 and -3 are suppressors for lymphomagenesis through the regulation of tumour suppressor genes Ikaros, Aiolos and FOXO3. Keywords: Egr-2, Egr-3, lymphocyte, tumour suppressor genes, Lymphoma Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Adaptive Immunity Citation: Bhullar PK, Miao T, Symonds AL, Ghaffari E, Li S and Wang P (2013). Early growth response gene 2 and 3 are essential for the regulation of tumour suppressor genes, Ikaros, Aiolos and FOXO3.. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00554 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Mrs. Punamdip K Bhullar, Brunel University, Bioscience, Uxbridge, Middelsex, UB8 3PH, United Kingdom, punamdip.bhullar@brunel.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Punamdip K Bhullar Tizong Miao Alistair L Symonds Emma Ghaffari Su-Ling Li Ping Wang Google Punamdip K Bhullar Tizong Miao Alistair L Symonds Emma Ghaffari Su-Ling Li Ping Wang Google Scholar Punamdip K Bhullar Tizong Miao Alistair L Symonds Emma Ghaffari Su-Ling Li Ping Wang PubMed Punamdip K Bhullar Tizong Miao Alistair L Symonds Emma Ghaffari Su-Ling Li Ping Wang Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Pathogen identification by nuclear imaging – almost there?

Invasive fungal disease (IFD) in immunocompromised patients is a major infective cause of morbidity and mortality, with rates of death up to 90 % [1]. A key factor is the challenge of early diagnosis of IFD. In patients with haematological malignancy following intensive chemotherapy, immunosuppression and/or allogeneic haematopoietic stem cell transplantation, it is rarely possible to obtain the diagnostic material to definitively establish the presence of an IFD. The reasons for this are multiple, and include profound pancytopenia and poor performance status, which make tissue sampling of the lung (the main site for invasive aspergillosis, IA) hazardous. Equally, laboratory biological tests for IA have shown limited efficacy in the setting of blood sampling [2, 3], whereas bronchoalveolar lavage fluid appears to be a better material to assay, but bronchoscopy is an invasive intervention and may not be possible in an ill patient. All these factors, combined with post-mortem data showing higher rates of IFD than diagnosed ante-mortem [4], have led to empirical therapy as the standard of care in many centres around the world. The definition of empirical IFD therapy used throughout the literature is the commencement of treatment based on the clinical scenario alone, with the commonest situation being persistent neutropenic fever despite the use of broad-spectrum antibiotics. However, building on recent clinical studies [5–7], current management algorithms for IFD emphasize the importance of attempting to make a diagnosis, rather than relying on an empirical approach alone [8, 9]. CT scanning of the chest has a central role in the management of IA, with characteristic findings (nodules with or without a halo, consolidation with cavitation or an air crescent sign) supporting the diagnosis of IFD [10]. However, as the gold standard of a histological diagnosis or culture from sterile material is rarely possible, it becomes immediately obvious that even in a diagnosis-driven strategy combining imaging and galactomannan detection (the only widely used biomarker for IA), treatment is usually given without definitive proof of IA! Furthermore, while imaging of the chest with CT can support the diagnosis of IA, there are numerous alternative infections, as well as other disease processes; and galactomannan detection itself is associated with falsenegatives, false-positives and issues of reproducibility. The paper by Petrik et al. [11] offers hope of moving the field forward by combining imaging with pathogen detection. They have exploited the dependence on iron of many microorganisms, including Aspergillus fumigatus. In ironlimiting environments, A. fumigatus produces large amounts of siderophores, which are iron-chelating peptides that scavenge Fe and facilitate its uptake back into the organism [12]. Siderophores are essential for A. fumigatus virulence and deletions of genes involved in siderophore biosynthesis significantly impair fungal virulence [13]. Petrik et al. have taken advantage of the similarity of iron and gallium chemistry, already widely exploited in the use of Ga citrate, to label two siderophores with the short-lived, generatorproduced isotope Ga. They found that both compounds had good in vitro characteristics with respect to stability and specific uptake into A. fumigatus in culture as demonstrated by competition by either excess iron or unlabelled siderophore. Using small-animal PET/CT imaging in an immunocompromised rat model of lung infection with A. fumigatus, S. G. Agrawal Division of Haemato-Oncology, St Bartholomews Hospital and Blizard Institute, Queen Mary University of London, London EC1A 7BE, UK

Stem cells: a potential target in colorectal cancer?

Colorectal CancerVol. 1, No. 1 EditorialStem cells: a potential target in colorectal cancer?Noor Jawad & Sir Nicholas WrightNoor JawadCentre for Digestive Diseases, Blizard Institute, Bart’s and the London School of Medicine & Dentistry, 4 Newark Street, Whitechapel, London E1 2AT, UKSearch for more papers by this author & Sir Nicholas Wright* Author for correspondenceSearch for more papers by this authorEmail the corresponding author at n.a.wright@qmul.ac.ukPublished Online:31 Jan 2012https://doi.org/10.2217/crc.11.7AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail View articleReferences1 Ahmed F. Effect of diet, lifestyle, and other environmental/chemopreventative factors on colorectal cancer development, and assessment of the risks. J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev.22,91–147 (2004).Crossref, Medline, CAS, Google Scholar2 Radtke F, Clevers H. Self-renewal and cancer of the gut: two sides of a coin. Science307(5717),1904–1909 (2005).Crossref, Medline, CAS, Google Scholar3 Hamburger AW, Salmon SE. Primary bioassay of human tumour stem cells. Science197(4302),461–463 (1977).Crossref, Medline, CAS, Google Scholar4 Bonnet D, Dick JE. Human acute myeloid leukaemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat. Med.3(7),730–737 (1997).Crossref, Medline, CAS, Google Scholar5 Cocciadiferro L, Miceli V, Kang KS, Polito LM, Trosko JE, Carruba G. Profiling cancer stem cells in androgen-responsive and refractory human prostate tumor cell lines. Ann. NY Acad. Sci.1155,257–262 (2009).Crossref, Medline, CAS, Google Scholar6 Dalerba P, Dylla SJ, Park IK et al. Phenotypic characterization of human colorectal cancer stem cells. Proc. Natl Acad. Sci. USA104,10158–10163 (2007).Crossref, Medline, CAS, Google Scholar7 O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature445,106–110 (2007).Crossref, Medline, Google Scholar8 Ricci-Vitiani L, Lombardi DG, Pilozzi E et al. Identification and expansion of human colon-cancer-initiating cells. Nature445,111–115 (2007).Crossref, Medline, CAS, Google Scholar9 Al-Hajj M. Prospective identification of tumourigenic breast cancer cells. Proc. Natl Acad. Sci. USA100(7),3983–3988 (2003).Crossref, Medline, CAS, Google Scholar10 Li C, Heidt DG, Dalerba P et al. Identification of pancreatic cancer stem cells. Cancer Res.67(3),1030–1037 (2007).Crossref, Medline, CAS, Google Scholar11 Singh SK, Clarke ID, Terasaki M et al. Identification of a cancer stem cell in human brain tumours. Cancer Res.63(18),5821–5828 (2003).Medline, CAS, Google Scholar12 Wicha MS, Liu S, Dontu G. Cancer stem cells: an old idea – a paradigm shift. Cancer Res.66(4),1883–1890; discussion 1895–1896 (2006).Crossref, Medline, CAS, Google Scholar13 Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature414(6859),105–111 (2001).Crossref, Medline, CAS, Google Scholar14 Vermeulen LTM, de Sousa Mello F, Sprick MR et al. Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity. Proc. Natl Acad. Sci. USA105(36),13427–13432 (2008).Crossref, Medline, CAS, Google Scholar15 Shmelkov SV, Butler JM, Hooper AT et al. CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors. J. Clin. Invest.118,2111–2120 (2008).Medline, CAS, Google Scholar16 Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ. Efficient tumour formation by single human melanoma cells. 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Cell Stem Cell1,389–402 (2007).Crossref, Medline, CAS, Google ScholarFiguresReferencesRelatedDetailsCited ByColorectal Cancer: a dedicated journal for a fast-moving fieldHeinz-Josef Lenz & Charlotte Barker31 January 2012 | Colorectal Cancer, Vol. 1, No. 1 Vol. 1, No. 1 Follow us on social media for the latest updates Metrics Downloaded 112 times History Published online 31 January 2012 Published in print February 2012 Information© Future Medicine LtdFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download

Holding solutions

1. Professor Mike Philpott, D.Phil (m.p.philpott{at}qmul.ac.uk) 2. Jamie Upton, BSc 1. Blizard Institute of Cell and Molecular Science, Barts and The London – Queen Mary’s School of Medicine and Dentistry London, UK There are a number of rationales behind the use of holding solutions for

Vitamin D: shining a light on autoimmune disease

Author for correspondence: Department of Clinical Neurology, University of Oxford, Oxford, UK and Blizard Institute of Cell & Molecular Science, Queen Mary University of London, Barts & The London School of Medicine and Dentistry, London, UK and The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK Tel.: +44 1865 287 659 Fax: +44 1865 287 501 sreeramr@well.ox.ac.uk Vitamin D: shining a light on autoimmune disease