Hydroxycarbamide: Mode of action. Jacques Elion, MD, PhD
|
|
|
- Dinah Bates
- 8 years ago
- Views:
Transcription
1 Hydroxycarbamide: Mode of action Jacques Elion, MD, PhD National Reference Centers for Sickle Cell Disease Department of Medical Genetics and UMR 665 Robert Debré University Hospital, 7519 Paris, France Guadeloupe University Hospital, Les Abymes (French West Indies) 3èmes Journées de la Drépanocytose en Martinique Trois Ilets février 213
2 HYDROXYCARBAMIDE (HC) Hydroxyurea is the only effective drug in SCD FDA 1998 (adults) EMEA 27 (adults and children) DROXIA Bristol-Myers Squibb SIKLOS AddMedica Initial expectation from HC: increased HbF expression deoxyhbs polymer decreased HbS polymerisation reduced vaso-occlusion Heterotetramer a2b S g HbF a2g2 Glu g Glu g
3 HYDROXYCARBAMIDE & Sickle Cell Disease but Oral HC : proven efficacy in clinical trials (adults & children) (Charache S et al, N Engl J Med 1995) Early clinical response Delayed and variable Hb F increase Ware RE, et al. Blood. 22;99:1-4
4 Induction of HbF by HC French pediatric trial Discordance 4 HbF (%) between clinical effect and 35 expected biological effect What are the targets of HC? What are the molecular mechanisms of HC action? treatment period (M) De Montalembert M, et al, J Pediatr Hematol, 1997, 19: Maier-Redelsperger M, et al. Blood, 1998, 91: UMR_S 665
5 In Sickle Cell Disease abnormal cell adhesion to the endothelium plays a major in targetting vaso-occlusion Mohandas & Evans, Blood 1984.but so does the vascular tone
6 Could HC affect cell adhesion? from JP Cartron SCADHESION project C Le Van Kim, PL Tharaux, J Elion - expression of adhesion molecules on RBCs? - endothelial cells? - leukocytes?
7 Could HC affect cell adhesion? from JP Cartron SCADHESION project C Le Van Kim, PL Tharaux, J Elion - expression of adhesion molecules on RBCs? - endothelial cells? - leukocytes?
8 Number of a4b1/ reticulocyte % of reticulocytes with overexpression of a4b1 SS reticulocytes express high levels of the a4b1 integrin (and CD36) 4 3 a4b1 2 1 Controls (n=8) HC (n=19) VOC (n=18) NonVOC (n=23) Controls (n=2) HC (n=2) VOC (n=18) Non VOC (n=23) Odièvre et al, Haematologica, 28
9 Number of a4b1/ reticulocyte % of reticulocytes with overexpression of a4b1 HC treatment reduces the expression of the a4b1 integrin (and CD36) on SS reticulocytes 4 3 a4b Controls (n=8) HC (n=19) VOC (n=18) NonVOC (n=23) Before HC On HC Controls (n=2) HC (n=2) VOC (n=18) Non VOC (n=23) Before HC On HC Odièvre et al, Haematologica, 28
10 Number of VLA-4 / GPA+ cell at J2 in vivo results are mimicked in vitro on erythroid progenitors in culture VLA-4 (a4b1) No HC With HC Odièvre et al, Haematologica, 28
11 Cellular targets of hydroxycarbamide in SCD RBCs - Hb F production - adhesion molecules - decreased production of a4b1 integrin, CD36 UMR 665
12 Mechanisms of sickle red blood cell adhesion: impact of HC treatment Epinephrine β2-ar HC PKA camp Sickle Red Blood Cell Gauthier et al, J Biol Chem 25 α4β1 integrin El Nemer et al, Blood 27 Lu/BCAM Endothelial cells Lu/BCAM Adhesion Less adhesion Laminin α5 Odièvre et al, Haematologica 28 Bartolucci et al, Blood 21 Abnormal cell-cell interactions in SCD are triggered by signalling events HC diminishes cell adhesion by inhibiting Lu/BCAM phosphorylation, independently of its expression level
13 Cellular targets of hydroxycarbamide in SCD RBCs - Hb F production - adhesion molecules - decreased production of a4b1 integrin, CD36 - decreased phosphorylation of Lu/BCAM UMR 665
14 Could HC affect cell adhesion? from JP Cartron SCADHESION project C Le Van Kim, PL Tharaux, J Elion - expression of adhesion molecules on RBCs? - endothelial cells? - leukocytes?
15 Travelling distance (µm) Emmanuelle Verger Microcinematic recording of RBCs submitted results dynamics on treated or untreated ECs RBC trajectories Time (s) 75 cells per experiment are individually traced at 2 msec intervals for each treatment condition 5 SS patients + 5 controls = 3. individual kinetics
16 mean advanced velocity (µm/s) Velocities of interacting (rolling?) SS-RBCs are lower than those of AA-RBCs greater interaction HPMEC *** *** NT cyt Emmanuelle Verger unpublished results RBC type/treatment of EC
17 mean advanced velocity (µm/s) HU treatment increases velocities of interacting (rolling?) RBCs reduces transient interactions HPMEC + HC 8 7 *** *** *** *** Emmanuelle Verger unpublished results NT HC cyt cyt+hc RBC type/treatment of EC
18 adherent RBC number /mm² AA-RBCs vs SS-RBCs firm adhesion on EC+/- HU (1dyne/cm 2 flow) * * basal inflammatory RBC type AARBC SSRBC AARBC SSRBC NT NT Emmanuelle Verger, unpublished results
19 adherent RBC number /mm² AA-RBCs vs SS-RBCs firm adhesion on EC+/- HU (1dyne/cm 2 flow) * * basal inflammatory + HC RBC type AARBC SSRBC AARBC SSRBC HC treatment NT HC NT HC After HC treatment of CE, adhesion potential of SS-RBCs is equivalent to that of AA-RBCs Emmanuelle Verger, unpublished results
20 Could HC affect cell adhesion? from JP Cartron SCADHESION project C Le Van Kim, PL Tharaux, J Elion - expression of adhesion molecules on RBCs? - endothelial cells: decreased adhesion - leukocytes?
21 Mechanism of action of HC on endothelial cells Sickle reticulocyte Laurance et al, Pharmacogenet Genomics 21 Haematologica 211 HC TSP-1 vwf PECAM-1 AMP PDE α4β1 integrin Less adhesion Adhesion Lu/BCAM Verger et al, submitted Chaar et al, submitted camp PKA AC HC inhibits the adhesive recruiting potential of endothelial cells by ATP modulating membrane adhesion Endothelial proteins cells and their activation state via phosphodiesterase activation
22 Cellular targets of hydroxycarbamide in SCD RBCs - Hb F production - adhesion molecules Endothelial cells - decreased adhesion vascular tone? UMR 665
23 ET-1(pg/ml) % of expression ET-1(pg/ml) HC also decreases endothelin-1 production by endothelial cells in culture Brun et al, 23, Pharmacogenomics J. mrna 12 Protein * p<.5 (n=5) 1 6 * * 8 4 * * 2 Control HC Cyto + HC NT HC Cyto Cyto + HC HC HC+Cyto TrHBMEC cells Incubation time : 48h HC ( M) HUVEC cells: identical results UMR 665
24 ET-1 (pg/ml) ET-1 (pg/ml) In vivo HU decreases ET-1 plasmatic levels Lapouméroulie et al, 25, Hematologica longitudinal follow up (two 8 year old SS girls) 14 months 16 months ,6 2 1,6 2 1,2 15 1,2 15,8 1,8 1,4 5, months months Decrease of plasmatic ET-1 does not correlate with HbF induction UMR 665
25 Cellular targets of hydroxycarbamide in SCD RBCs - Hb F production - adhesion molecules Endothelial cells - decreased adhesion - decreased production of endothelin-1 vasoconstriction UMR 665
26 Could HC affect cell adhesion?? from JP Cartron SCADHESION project C Le Van Kim, PL Tharaux, J Elion - expression of adhesion molecules on RBCs? - endothelial cells? - leukocytes?
27 HC normalizes L-selectin expression and H 2 2 production by PMNs of SCD patients in vivo Benkerrou et al Blood, ** 1 ** 8 controls (n=11) 6 4 ** ** severe SS patients (n=17) HU treated (n=9) H 2 2 production L-selectin by whole blood PMNs stimulated with TNFa and fmlp expressed at the surface of fmlp-stimulated PMNs UMR 665
28 Cellular targets of hydroxycarbamide in SCD RBCs - Hb F production - adhesion molecules Endothelial cells - adhesion molecules - endothelin-1 Polymorphonuclear neutrophils - activation UMR 665
29 Conclusions HC has a pleiotropic action in SCD HC decreases deoxy HbS polymerisation - HbF expression - RBC hydration HC decreases cellular adhesion to endothelium - proadhesive RBCs - adhesion properties of ECs - PMN activation HC decreases vasoconstrictive stimulus - ET-1
30 Paris Guadeloupe Pointe-à-Pitre UMR 665 Institut national de la santé et de la recherche médicale Réunion
Adhésion à l endothélium dans la drépanocytose
Adhésion à l endothélium dans la drépanocytose Jacques Elion Départment de Génétique et INSERM UMR 763 Hôpital Robert Debré, 75019 Paris et CHU de Pointe à Pitre, 97139 Les Abymes Centre de Référence Francilien
Danitza Nébor, Ph.D.
Danitza Nébor, Ph.D. Professional contact Jackson Laboratory 600 Main Street Bar Harbor, ME 04609 Email: Danitza.nebor@jax.org Education Post- doctoral associate The Jackson laboratory Oct 2012 - present
Effets biologiques des facteurs de croissance sur la régénération musculaire
Effets biologiques des facteurs de croissance sur la régénération musculaire Xavier Bigard (MD, PhD) Professeur Agrégé du Val-de-Grâce Institut de Recherche Biomédicale des Armées (IRBA) La Tronche (Grenoble)
How To Treat Mesothelioma With A Tumor Stem Cell Inhibitor
FAK INHIBITOR DEFACTINIB (VS-6063) TARGETS MESOTHELIOMA CANCER STEM CELLS Rationale for maintenance therapy after conventional therapy Jonathan Pachter, Ph.D. Vice President of Research, Verastem, Inc.
Ariela Benigni. Biol.Sci.D., Ph.D. Curriculum Vitae
Ariela Benigni Biol.Sci.D., Ph.D. Curriculum Vitae Personal Data Name: Date and place of birth: Citizenship: E-mail: Ariela Benigni December 16, 1955 - Bergamo, Italy Italian ariela.benigni@marionegri.it
Application Note No. 2 / July 2012. Quantitative Assessment of Cell Quality, Viability and Proliferation. System
Application Note No. 2 / July 2012 Quantitative Assessment of Cell Quality, Viability and Proliferation System Quantitative Assessment of Cell Quality, Viability and Proliferation Introduction In vitro
Actions of Hormones on Target Cells Page 1. Actions of Hormones on Target Cells Page 2. Goals/ What You Need to Know Goals What You Need to Know
Actions of Hormones on Target Cells Graphics are used with permission of: Pearson Education Inc., publishing as Benjamin Cummings (http://www.aw-bc.com) Page 1. Actions of Hormones on Target Cells Hormones
Blood Sticky, opaque fluid with a metallic taste (Fe 2+ ) Varies from scarlet (P O2 = 100) to dark red (P O2 = 40) ph is between 7.35 and 7.45 Average volume in an adult is 5 L (7% of body weight) 2 L
Perioperative management of Dual Antiplatelet therapy post drug eluting stent-changing time
Perioperative management of Dual Antiplatelet therapy post drug eluting stent-changing time Robert Chilton DO, FACOI, FACC, FAHA Professor of Medicine University of Texas Health Science Center Director
Pulmonary Hypertension in Sickle Cell Disease. Jorge Ramos Hematology Fellows Conference June 28, 2013
Pulmonary Hypertension in Sickle Cell Disease Jorge Ramos Hematology Fellows Conference June 28, 2013 Patient Presentation 28F with SCD, genotype SS. Presented to UWMC ER with 1 month progressive DOE and
Chapter-21b: Hormones and Receptors
1 hapter-21b: Hormones and Receptors Hormone classes Hormones are classified according to the distance over which they act. 1. Autocrine hormones --- act on the same cell that released them. Interleukin-2
Chapter 4 Pedigree Analysis in Human Genetics. Chapter 4 Human Heredity by Michael Cummings 2006 Brooks/Cole-Thomson Learning
Chapter 4 Pedigree Analysis in Human Genetics Mendelian Inheritance in Humans Pigmentation Gene and Albinism Fig. 3.14 Two Genes Fig. 3.15 The Inheritance of Human Traits Difficulties Long generation time
Therapeutic Treatment Options: Chronic Blood Transfusions Bone Marrow Transplantation. Marianne E. McPherson Yee, MD, MSc
Therapeutic Treatment Options: Chronic Blood Transfusions Bone Marrow Transplantation Marianne E. McPherson Yee, MD, MSc Sickle Cell Treatment Options Supportive Care Newborn Screen PCN Immunizations Education
Vascular Effects of Caffeine
Vascular Effects of Caffeine John P. Higgins MD, MBA, MPHIL, FACC, FACP, FAHA, FACSM, FASNC, FSGC Director of Exercise Physiology Memorial Hermann Sports Medicine Institute Chief of Cardiology, Lyndon
AAGPs TM Anti-Aging Glyco Peptides. Enhancing Cell, Tissue and Organ Integrity Molecular and biological attributes of lead AAGP molecule
AAGPs TM Anti-Aging Glyco Peptides Enhancing Cell, Tissue and Organ Integrity Molecular and biological attributes of lead AAGP molecule 1 Acknowledgements This presentation was prepared by Dr. Samer Hussein
Biotechnology. Srivatsan Kidambi, Ph.D.
Stem Stem Cell Cell Engineering-What, Biology and it Application Why, How?? to Biotechnology Srivatsan Kidambi, Ph.D. Assistant Professor Department of Chemical & Biomolecular Engineering University of
Stroke & Alzheimer s Disease: An Inflammatory Duo
Stroke & Alzheimer s Disease: An Inflammatory Duo Stroke and Dementia One in 3 will experience a stroke, dementia or both 64% of persons with a stroke have some degree of cognitive impairment and up to
Electronic Medical Records and Genomics: Possibilities, Realities, Ethical Issues to Consider
Electronic Medical Records and Genomics: Possibilities, Realities, Ethical Issues to Consider Daniel Masys, M.D. Affiliate Professor Biomedical and Health Informatics University of Washington, Seattle
Prioritizing Comparative Effectiveness Research Questions: PCORI Stakeholder Workshops. March 7, 2016
Prioritizing Comparative Effectiveness Research Questions for Management of Sickle Cell Disease: Questions submitted for consideration by workshop participants Prioritizing Comparative Effectiveness Research
The Immunopathogenesis of Relapsing MS
The Immunopathogenesis of Relapsing MS Olaf Stüve, M.D., Ph.D. Neurology Section VA North Texas Health Care System Dallas VA Medical Center Departments of Neurology and Neurotherapeutics University of
Mechanisms of Interferon-associated Bone Marrow Suppression with or without Ribavirin. K. Zhdanov
EASL endorsed conference White Nights of Hepatology 2012 Adverse events during antiviral therapy: how to predict, manage and monitor June 7-8 Saint-Petersburg Mechanisms of Interferon-associated Bone Marrow
Rheumatoid arthritis: an overview. Christine Pham MD
Rheumatoid arthritis: an overview Christine Pham MD RA prevalence Chronic inflammatory disease affecting approximately 0.5 1% of the general population Prevalence is higher in North America (approaching
treatments) worked by killing cancerous cells using chemo or radiotherapy. While these techniques can
Shristi Pandey Genomics and Medicine Winter 2011 Prof. Doug Brutlag Chronic Myeloid Leukemia: A look into how genomics is changing the way we treat Cancer. Until the late 1990s, nearly all treatment methods
Vivia Test AML: Test de Medicina Personalizada para el tratamiento de la Leucemia Mieloide Aguda
Vivia Test AML: Test de Medicina Personalizada para el tratamiento de la Leucemia Mieloide Aguda Joan Ballesteros, PhD Chief Scientific Officer Joaquin Martinez Medical Director Andres Ballesteros, CEO
Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction
Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction Esther Lopez Garcia, Matthias B Schulze, Teresa T Fung, James B Meigs, Nader Rifai, JoAnn
Avastin in breast cancer: Summary of clinical data
Avastin in breast cancer: Summary of clinical data Worldwide, over one million people are diagnosed with breast cancer every year 1. It is the most frequently diagnosed cancer in women 1,2, and the leading
Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation
Identification of rheumatoid arthritis and osterthritis patients by transcriptome-based rule set generation Bering Limited Report generated on September 19, 2014 Contents 1 Dataset summary 2 1.1 Project
Hypersensitivity. TYPE I Hypersensitivity Classic allergy. Allergens. Characteristics of allergens. Allergens. Mediated by IgE attached to Mast cells.
Gel and Coombs classification of hypersensitivities. Hypersensitivity Robert Beatty Type I Type II Type III Type IV MCB150 IgE Mediated IgG/IgM Mediated IgG Mediated T cell Classic Allergy rbc lysis Immune
SCD Young Adult Transition
SCD Young Adult Transition Julie Kanter, MD Director, Sickle Cell Disease Research Assistant Professor, Pediatric Heme-Onc Medical University of South Carolina Disclosure MUSC receives funding from multiple
Modulating Glucose Uptake in Skeletal Myotubes:
icell Skeletal Myoblasts Application Protocol Introduction Modulating Glucose Uptake in Skeletal Myotubes: Insulin Induction with Bioluminescent Glucose Uptake Analysis The skeletal muscle is one of the
Genetic testing. The difference diagnostics can make. The British In Vitro Diagnostics Association
6 Genetic testing The difference diagnostics can make The British In Vitro Diagnostics Association Genetic INTRODUCTION testing The Department of Health published Our Inheritance, Our Future - Realising
Evaluation of focal adhesions as new therapeutic targets in acute myeloid leukemia
Evaluation of focal adhesions as new therapeutic targets in acute myeloid leukemia Dr Jordi Sierra Gil IRHSP Institut de Recerca Hospital de la Santa Creu i Sant Pau Dr. Miguel Ángel Sanz Alonso Fundación
Siklos for Sickle cell anaemia
West Midlands Strategic Commissioning Group Commissioning Policy (WM/26) Siklos for Sickle cell anaemia Version 1 September 2010 1. Definitions A licensed medicine is a product with a marketing authorisation
Basic Science in Medicine
Medical Journal of th e Islamic Republic of Iran Volume 18 Number 3 Fall 1383 November 2004 Basic Science in Medicine ] EXPANSION OF HUMAN CORD BLOOD PRIMITIVE PROGENITORS IN SERUM-FREE MEDIA USING HUMAN
New Treatment Options for MS Patients: Understanding risks versus benefits
New Treatment Options for MS Patients: Understanding risks versus benefits By Michael A. Meyer, MD Department of Neurology, Sisters Hospital, Buffalo, NY Objectives: 1. to understand fundamentals of MS
Platelet Review July 2012. Thomas S. Kickler M.D. Johns Hopkins University School of Medicine
Platelet Review July 2012 Thomas S. Kickler M.D. Johns Hopkins University School of Medicine Hemostasis Hemostasis is the process that leads to the stopping of bleeding Hemostasis involves blood vessels,
Inflammatory Cytokine-induced Expression of Vasohibin-1 by Rheumatoid Synovial Fibroblasts
9 6 6 958 Inflammatory Cytokine-induced Expression of Vasohibin- by Rheumatoid Synovial Fibroblasts a b c a a a a d e a* a a b c d e 5 6 6 9 5 56 67 7 ʼ ʼ ʼ ʼ ʼ ʼ ʼ ʼ 5 6 6 ʼ 5 75 989 6 69 8 95 56 56896
Development & Validation of a Web-based Decision Aid to Facilitate Shared Decision Making in Sickle Cell Disease by Patients & Families
Development & Validation of a Web-based Decision Aid to Facilitate Shared Decision Making in Sickle Cell Disease by Patients & Families L. Krishnamurti, D. Ross, N. Bakshi,A. Williams*, P. Lane, G. Loewenstein**
Cord Blood for Cellular Therapy: A Snapshot of this Evolving Market Landscape
GENReports: Market & Tech Analysis Cord Blood for Cellular Therapy: A Snapshot of this Evolving Market Landscape > Enal Razvi, Ph.D. Biotechnology Analyst, Managing Director SELECTBIO US enal@selectbio.us
Regulations for Handling Samples and Laboratory Testing from R&D through Phase III Clinical Trials
Regulations for Handling Samples and Laboratory Testing from R&D through Phase III Clinical Trials Ron Hinkel, Director Quality Systems BioReliance Inc. Patti Rossman, President Globiox Purpose Keep pace
The Need for a PARP in vivo Pharmacodynamic Assay
The Need for a PARP in vivo Pharmacodynamic Assay Jay George, Ph.D., Chief Scientific Officer, Trevigen, Inc., Gaithersburg, MD For further infomation, please contact: William Booth, Ph.D. Tel: +44 (0)1235
Causes of Anemia in Patients with Heart Failure. Adriaan Voors, MD, PhD, Cardiologist Professor of Cardiology, UMC Groningen, Netherlands
Causes of Anemia in Patients with Heart Failure Adriaan Voors, MD, PhD, Cardiologist Professor of Cardiology, UMC Groningen, Netherlands Background Anemia is common in patients with CHF Prevalence 15 55%
Hematopoietic Stem Cell Transplant for Sickle cell disease What a pediatrician ought to know
Hematopoietic Stem Cell Transplant for Sickle cell disease What a pediatrician ought to know Allistair Abraham, MD Division of Blood and Marrow Transplantation Outline Background Sickle cell disease Matched
BSc in Medical Sciences with PHARMACOLOGY
BSc in Medical Sciences with PHARMACOLOGY Course Director Dr Christopher John Module Leaders Dr Robert Dickinson (Module 1) Dr Anabel Varela Carver (Module 2) Dr Sohag Saleh (Module 3) Course Administrator
Genomic Medicine The Future of Cancer Care. Shayma Master Kazmi, M.D. Medical Oncology/Hematology Cancer Treatment Centers of America
Genomic Medicine The Future of Cancer Care Shayma Master Kazmi, M.D. Medical Oncology/Hematology Cancer Treatment Centers of America Personalized Medicine Personalized health care is a broad term for interventions
Fight or Flight Response: Play-by-Play
One of the most remarkable examples of cell communication is the fight or flight response. When a threat occurs, cells communicate rapidly to elicit physiological responses that help the body handle extraordinary
B Cells and Antibodies
B Cells and Antibodies Andrew Lichtman, MD PhD Brigham and Women's Hospital Harvard Medical School Lecture outline Functions of antibodies B cell activation; the role of helper T cells in antibody production
Zebrafish Chemical Screens
Zebrafish Chemical Screens 1 Historical look at zebrafish chemical screens 2 The effects of AAF on embryonic development in relation to its carcinogenic role 3 First generation Screens HISAOKA, K. K. (1958).
FACULTY OF MEDICAL SCIENCE
Doctor of Philosophy in Biochemistry FACULTY OF MEDICAL SCIENCE Naresuan University 73 Doctor of Philosophy in Biochemistry The Biochemistry Department at Naresuan University is a leader in lower northern
ALPHA (TNFa) IN OBESITY
THE ROLE OF TUMOUR NECROSIS FACTOR ALPHA (TNFa) IN OBESITY Alison Mary Morris, B.Sc (Hons) A thesis submitted to Adelaide University for the degree of Doctor of Philosophy Department of Physiology Adelaide
Coxib s have taught us a lesson to explore more diligently the molecular and cellular pathways of inflammation
Coxib s have taught us a lesson to explore more diligently the molecular and cellular pathways of inflammation Steffen Gay Arthritis linked to cardiovascular disease CV Death Osteoarthritis CHF Rheumatoid
Modelling cell motion: From microscopic to macroscopic scale. Luigi Preziosi Luigi.preziosi@polito.it calvino.polito.it/~preziosi
Modelling cell motion: From microscopic to macroscopic scale Luigi Preziosi Luigi.preziosi@polito.it calvino.polito.it/~preziosi Modelling cell-ecm interaction: An opportunity to present different modelling
BY2012 Microbiology Bacterial Fimbriae & Adherence
BY2012 Microbiology Bacterial Fimbriae & Adherence Bacterial Fimbriae Fimbriae Flagella Colourised electron micrograph of an Escherichia coli cell bearing type 1 fimbriae Escherichia coli with Type 1 Fimbriae
Cord Blood Market Trends, circa 2014
GENReports: Market & Tech Analysis Cord Blood Market Trends, circa 2014 > Enal Razvi, Ph.D. Managing Director Select Biosciences, Inc. enal@selectbio.us Topic Introduction and Scope The focus of this GEN
Interleukin-17A (IL-17) is the signature cytokine secreted by
The Journal of Immunology IL-17 and TNF-a Sustain Neutrophil Recruitment during Inflammation through Synergistic Effects on Endothelial Activation Gabriel K. Griffin,*, Gail Newton, Margarite L. Tarrio,
20.309: Biological Instrumentation and Measurement. Heejin Choi Rumi Chunara Yuri Matsumoto
20.309: Biological Instrumentation and Measurement Instructors: Laboratory Instructor: Teaching Assistants: Scott Manalis and Peter So Steve Wasserman Jaewon Cha Heejin Choi Rumi Chunara Yuri Matsumoto
Targeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma
The Use of Kinase Inhibitors: Translational Lab Results Targeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma Sheelu Varghese, Ph.D. H. Richard Alexander, M.D.
Thibodeau: Anatomy and Physiology, 5/e. Chapter 17: Blood
Thibodeau: Anatomy and Physiology, 5/e Chapter 17: Blood This chapter begins a new unit. In this unit, the first four chapters deal with transportation one of the body's vital functions. It is important
Prevention of Acute COPD exacerbations
December 3, 2015 Prevention of Acute COPD exacerbations George Pyrgos MD 1 Disclosures No funding received for this presentation I have previously conducted clinical trials with Boehringer Ingelheim. Principal
LEUKEMIA LYMPHOMA MYELOMA Advances in Clinical Trials
LEUKEMIA LYMPHOMA MYELOMA Advances in Clinical Trials OUR FOCUS ABOUT emerging treatments Presentation for: Judith E. Karp, MD Advancements for Acute Myelogenous Leukemia Supported by an unrestricted educational
Biological cell membranes
Unit 14: Cell biology. 14 2 Biological cell membranes The cell surface membrane surrounds the cell and acts as a barrier between the cell s contents and the environment. The cell membrane has multiple
In vitro co-culture model of the inflamed intestinal mucosa
In vitro co-culture model of the inflamed intestinal mucosa Berlin, December 13, 2011 Eva-Maria Collnot, e.collnot@mx.uni-saarland.de Helmholtz Institute for Pharmaceutical Research Saarland Departement
Improving EGFR kinase inhibitor design for the targeted treatment of lung cancer.
Improving EGFR kinase inhibitor design for the targeted treatment of lung cancer. Shannon Tarby, Earl Benjamin III, and Ellis Benjamin Department of Chemistry, Richard Stockton College of New Jersey, 101
Viral load testing. medical monitoring: viral load testing: 1
medical monitoring: viral load testing: 1 medical monitoring: viral load testing Viral load testing medical monitoring: viral load testing: 2 Slide 1 Viral load The viral load test measures HIV in the
Seahorse XF Cell Mito Stress Test Kit
Seahorse XF Cell Mito Stress Test Kit Part # 103015-100 User Guide For use with Seahorse XF e and XF Extracellular Flux Analyzers For Research Use Only 1 Table of Contents Product Description... 2 Introduction...
Pl I enary Tr T anslational Medicine April 30, 2015
Plenary I Translational Medicine April 30, 2015 HBO in Hematopoietic Stem Cell Transplantation: Lessons Learned Omar Aljitawi, MD Hematology/Oncology Hematology and Transplantation (HAT) Laboratory Pathology
Genetic Alliance BioBank: A Virtual Tour of Registry Solutions to Accelerate Research February 22, 2010
Genetic Alliance BioBank: A Virtual Tour of Registry Solutions to Accelerate Research February 22, 2010 Liz Horn Genetic Alliance Posted in the Resource Repository at: http://www.resourcerepository.org/documents/1872/geneticalliancebiobank:avirtualto
Disclosure. New Agents for Treatment of DVT. Prevalence of DVT VTE. Normal Hemostasis 7/17/2015. Mark Oliver, MD, RVT, RPVI,FSVU
New Agents for Treatment of DVT Disclosure PI Adopt and Amplify trials Mark Oliver, MD, RVT, RPVI,FSVU BMS and Pfizer Speaker VTE Venous Thromboembolism Recognized DVT s New : 170,000 Recurrent : 90,000
Hydroxyurea Treatment for Sickle Cell Disease
Hydroxyurea Treatment for Sickle Cell Disease Before hydroxyurea After hydroxyurea Hydroxyurea Treatment for Sickle Cell Disease 1 This document is not intended to take the place of the care and attention
CYP2B6 and NAT2 genetic polymorphisms enlighten the pharmacokinetic interaction of efavirenz with rifampicin and isoniazid - ANRS 12154 trial
CYP2B6 and NAT2 genetic polymorphisms enlighten the pharmacokinetic interaction of efavirenz with rifampicin and isoniazid - ANRS 12154 trial Julie Bertrand 1,2, Céline Verstuyft 3,4, Monidarin Chou 5,
Avastin in breast cancer: Summary of clinical data
Avastin in breast cancer: Summary of clinical data Worldwide, over one million people are diagnosed with breast cancer every year 1. It is the most frequently diagnosed cancer in women 1,2, and the leading
Gene Therapy. The use of DNA as a drug. Edited by Gavin Brooks. BPharm, PhD, MRPharmS (PP) Pharmaceutical Press
Gene Therapy The use of DNA as a drug Edited by Gavin Brooks BPharm, PhD, MRPharmS (PP) Pharmaceutical Press Contents Preface xiii Acknowledgements xv About the editor xvi Contributors xvii An introduction
Degree Requirements for the Forensic Science Program
Degree Requirements for the Forensic Science Program BS in Forensic Science (59 hours) Prepares students for graduate studies forensic science. (Positions in a forensic science laboratory generally require
VPM 152. INFLAMMATION: Chemical Mediators
General Pathology VPM 152 INFLAMMATION: Chemical Mediators CHEMICAL MEDIATORS OF INFLAMMATION Definition: any messenger that acts on blood vessels, inflammatory cells or other cells to contribute to an
KEY CHAPTER 14: BLOOD OBJECTIVES. 1. Describe blood according to its tissue type and major functions.
KEY CHAPTER 14: BLOOD OBJECTIVES 1. Describe blood according to its tissue type and major functions. TISSUE TYPE? MAJOR FUNCTIONS connective Transport Maintenance of body temperature 2. Define the term
Immunosuppressive drugs
Immunosuppressive drugs RJM ten Berge Afd. Inw. Geneeskunde AMC contents overview targets mechanism of action Effects on immune capacity measured by responses to vaccination Immune response 1 calcineurin
Cardiovascular System. Blood Components
Cardiovascular System Blood Components 1 Components of Blood Formed elements: erythrocytes, leukocytes, platelets Plasma: water, proteins, other solutes The components of blood can be divided into two
Call 2014: High throughput screening of therapeutic molecules and rare diseases
Call 2014: High throughput screening of therapeutic molecules and rare diseases The second call High throughput screening of therapeutic molecules and rare diseases launched by the French Foundation for
UNIVERSITY OF DEBRECEN MEDICAL AND HEALTH SCIENCE CENTER
THESES OF Ph.D. The changes of leukocyte-platelet mixed aggregates formation, platelet EDRF/NO production, and haemorheology in diabetes mellitus, their role in the pathogenesis of diabetic angiopathy
Public Cord Blood Banking at the National Cord Blood Program (NCBP)
Public Cord Blood Banking at the National Cord Blood Program (NCBP) A. Scaradavou, MD Medical Director, National Cord Blood Program, New York Blood Center Associate Attending, Pediatric BMT Memorial Sloan-Kettering
Exelixis Showcases R&D Pipeline at JPMorgan Healthcare Conference
Exelixis Showcases R&D Pipeline at JPMorgan Healthcare Conference Two New Clinical Programs and Significant Expansion of Cancer Pipeline Planned for 2004 SOUTH SAN FRANCISCO, Calif., Jan. 13 /PRNewswire-FirstCall/
Hepatitis C treatment update
Hepatitis C treatment update Viral Hepatitis Workshop Hepatitis Foundation and Regional Public Health December 2013 Jeffrey S Wong Hepatitis C treatment Non-A non-b hepatitis History of HCV treatment Hutt
Europass Curriculum Vitae
Europass Curriculum Vitae Personal information First name(s) / Surname(s) Address(es) Department of Molecular Immunology, Viale Regina Elena 329 00161-Rome Italy Telephone(s) +39 06 49970517/ +39 06 49970586
Non-clinical development of biologics
Aurigon Life Science GmbH Non-clinical development of biologics Requirements, challenges and case studies Committed to Life. Sigrid Messemer vet. med. M4 Seminar March 10 th 2014 Aurigon - your full service
Collect and label sample according to standard protocols. Gently invert tube 8-10 times immediately after draw. DO NOT SHAKE. Do not centrifuge.
Complete Blood Count CPT Code: CBC with Differential: 85025 CBC without Differential: 85027 Order Code: CBC with Differential: C915 Includes: White blood cell, Red blood cell, Hematocrit, Hemoglobin, MCV,
Teriflunomide is the active metabolite of Leflunomide, a drug employed since 1994 for the treatment of rheumatoid arthritis (Baselt, 2011).
Page 1 of 10 ANALYTE NAME AND STRUCTURE TERIFLUNOMIDE Teriflunomide TRADE NAME Aubagio CATEGORY Antimetabolite TEST CODE PURPOSE Therapeutic Drug Monitoring GENERAL RELEVANCY BACKGROUND sclerosis. The
How To Understand The Effects Of A Drug On Your Health
Farmacologia degli inibitori TK e mtor Romano Danesi Professore ordinario di Farmacologia UOC Farmacologia Universitaria Azienda Ospedaliero-Universitaria Pisana Dipartimento di Medicina Interna Università
Big Data Problem? or Big Problem with Data? William Hayes, PhD SVP PlaCorm Dev, Selventa
Big Data Problem? or Big Problem with Data? William Hayes, PhD SVP PlaCorm Dev, Selventa 2013, Selventa. All Rights Reserved. Confiden;al 1 Who am I? ex- Aerospace Engineer Defected to Bioinforma;cs (PhD
博 士 論 文 ( 要 約 ) A study on enzymatic synthesis of. stable cyclized peptides which. inhibit protein-protein interactions
博 士 論 文 ( 要 約 ) 論 文 題 目 A study on enzymatic synthesis of stable cyclized peptides which inhibit protein-protein interactions ( 蛋 白 質 間 相 互 作 用 を 阻 害 する 安 定 な 環 状 化 ペプチドの 酵 素 合 成 に 関 する 研 究 ) 氏 名 張 静 1
An Overview of Cells and Cell Research
An Overview of Cells and Cell Research 1 An Overview of Cells and Cell Research Chapter Outline Model Species and Cell types Cell components Tools of Cell Biology Model Species E. Coli: simplest organism
GENETIC PROFILES AND TARGETED TREATMENT OF CANCER - PERSONALIZED MEDICINE
GENETIC PROFILES AND TARGETED TREATMENT OF CANCER - PERSONALIZED MEDICINE Branko Zakotnik MD, PhD Department of Medical Oncology Institute of Oncology Ljubljana 1 I have no conflict of interest to declare
CURRICULUM VITAE ROBERTO GIACOMELLI MD, PhD
CURRICULUM VITAE ROBERTO GIACOMELLI MD, PhD NAME Roberto Giacomelli TITLE Full Professor of Rheumatology, University of L Aquila, School of Medicine, L Aquila, Italy NATIONALITY Italian ADDRESS Permanent:
Mobile Applications in Apheresis
Mobile Applications in Apheresis Anand Padmanabhan, MD PhD Medical Director, BloodCenter of Wisconsin Associate Investigator, Blood Research Institute Assistant Professor of Pathology, Medical College
Overview of Phase 1 Oncology Trials of Biologic Therapeutics
Overview of Phase 1 Oncology Trials of Biologic Therapeutics Susan Jerian, MD ONCORD, Inc. February 28, 2008 February 28, 2008 Phase 1 1 Assumptions and Ground Rules The goal is regulatory approval of
International Aloe Science Council Certified Facility and Products
Aloe vera L. Simply, the most extensively tested Aloe vera available Aloecorp, Inc International Aloe Science Council Certified Facility and Products Qmatrix The GRAS Ingredient A Highly Purified Fraction
Blood. Blood. Blood Composition. Blood Composition. Fractionation & Hemopoesis
Blood Blood Chapter 19 Blood is a specialized fluid connective tissue that contains cells suspended in a fluid matrix Functions of blood include: Transport of dissolved gases, nutrients, hormones and metabolic
STEM CELL FELLOWSHIP
Module I: The Basic Principles of Stem Cells 1. Basics of Stem Cells a. Understanding the development of embryonic stem cells i. Embryonic stem cells ii. Embryonic germ cells iii. Differentiated stem cell
CAS Chemistry Research Report Delivering the latest trends in global chemistry research
Delivering the latest trends in global chemistry research Human Genome Discoveries Spur Growth of Cancer Treatments www.cas.org Strength of the Human Genome Project and Targeted Drugs In, President Clinton
Understanding West Nile Virus Infection
Understanding West Nile Virus Infection The QIAGEN Bioinformatics Solution: Biomedical Genomics Workbench (BXWB) + Ingenuity Pathway Analysis (IPA) Functional Genomics & Predictive Medicine, May 21-22,
COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) NOTE FOR GUIDANCE ON THE PRE-CLINICAL EVALUATION OF ANTICANCER MEDICINAL PRODUCTS
The European Agency for the Evaluation of Medicinal Products Human Medicines Evaluation Unit London, 23 July 1998 COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) NOTE FOR GUIDANCE ON THE PRE-CLINICAL