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Dupilumab in Children with Uncontrolled Moderate-to-Severe Asthma

四川生理科学杂志 2021年第10期43卷 1816-1816页

作者： Leonard B Bacharier From Monroe Carell Jr. Children's Hospital at Vanderbilt Nashville (L.B.B.) Fundación CIDEA Buenos Aires (J.F.M.) Campbelltown Hospital Campbelltown NSW and Western Sydney University Sydney (C.H.K.) - both in Australia Bambino Gesù Children's Hospital IRCCS Rome (A.G.F.) Clinique Spécialisée en Allergie de la Capitale Quebec QC Canada (R.G.) Hospital Vall d'Hebron Barcelona (I.M.) Arizona Allergy and Immunology Research Gilbert (N.J.) Peninsula Research Associates Rolling Hills Estates CA (L.D.S.) Sanofi Bridgewater NJ (X.M. U.K. P.J.R. E.L.) Sanofi Beijing (D.L.) regeneron pharmaceuticals Tarrytown NY (Y.Z. F.A.K. Y.D. M.R. D.M.W. G.D.Y. N.A. D.J.L.) Sanofi Chilly-Mazarin France (A.H.K. L.P.M.) and Sanofi Genzyme Cambridge MA (N.P. M.H.).

Background:Children with moderate-to-severe asthma continue to have disease complications despite the receipt of standardof-care *** monoclonal antibody dupilumab has been approved for the treatment of adults and adolescents with asthma as well as with other type 2 inflammatory ***:In this 52-week phase 3,randomized,double-blind,placebo-controlled trial,we assigned 408 children between the ages of 6 and 11 years who had uncontrolled moderate-to-severe asthma to receive a subcutaneous injection of dupilumab(at a dose of 100 mg for those weighing≤30 kg and 200 mg for those weighing>30 kg)or matched placebo every 2 *** the children continued to receive a stable dose of standard background *** primary end point was the annualized rate of severe asthma *** end points included the change from baseline in the percentage of predicted prebronchodilator forced expiratory volume in 1 second(ppFEV1)at week 12 and in the score on the Asthma Control Questionnaire 7 Interviewer-Administered(ACQ-7-IA)at week *** points were evaluated in the two primary efficacy populations who had either a type 2 inflammatory asthma phenotype(≥150 blood eosinophils per cubic millimeter or a fraction of exhaled nitric oxide of≥20 ppb at baseline)or a blood eosinophil count of at least 300 cells per cubic millimeter at baseline.

关键词： millimeter cubic continued

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Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis

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四川生理科学杂志 2022年第12期44卷 2116-2116页

作者： Evan S Dellon From the Center for Esophageal Diseases and Swallowing University of North Carolina School of Medicine Chapel Hill (E.S.D.) Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine Cincinnati (M.E.R. M.H.C.) Northwestern University Feinberg School of Medicine Chicago (I.H.) Mount Sinai Center for Eosinophilic Disorders Icahn School of Medicine at Mount Sinai New York (M.C.) and Regeneron Pharmaceuticals Tarrytown (X.S. M.P.K. M.A.K. J.D.H. B.B. E.M. B.A. N.A. W.K.L. M.F.W. M.R. D.R.W. G.D.Y. B.S. J.M. A.G. A.S.) - both in New York Amsterdam University Medical Center Amsterdam (A.J.B.) Hospital General de Tomelloso Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas Madrid and Instituto de Investigación Sanitaria de Castilla-La Mancha Toledo - both in Spain (A.J.L.) Children's Hospital of Philadelphia Philadelphia (J.M.S.) University of California San Diego La Jolla and Rady Children's Hospital San Diego - both in California (S.A.) Sanofi Bridgewater NJ (K.P. E.L.) Sanofi Chilly-Mazarin France (L.P.M.) and Sanofi Cambridge MA (N.P.).

Background:Dupilumab,a fully human monoclonal antibody,blocks interleukin-4 and interleukin-13 signaling,which have key roles in eosinophilic ***:We conducted a three-part,phase 3 trial in which patients 12 years of age or older underwent randomization in a 1:1 ratio to receive subcutaneous dupilumab at a weekly dose of 300 mg or placebo(Part A)or in a 1:1:1 ratio to receive 300 mg of dupilumab either weekly or every 2 weeks or weekly placebo(Part B)up to week 24.

关键词： monoclonal placebo weekly

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Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome

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四川生理科学杂志 2023年第10期45卷 1848-1848页

作者： Gregory G Schwartz From the Division of Cardiology University of Colorado School of Medicine Aurora (G.G.S.) Assistance Publique–Hôpitaux de Paris Hôpital Bichat Paris Diderot University Sorbonne Paris Cité FACT (French Alliance for Cardiovascular Trials) and INSERM Unité 1148 (P.G.S.) and Sanofi (C.H. G.L.) — all in Paris the National Heart and Lung Institute Imperial College Royal Brompton Hospital London (P.G.S.) the State University of New York Downstate School of Public Health Brooklyn (M.S.) and Regeneron Pharmaceuticals Tarrytown (R.P. W.J.S.) — both in New York Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School Boston (D.L.B.) the Division of Cardiovascular Disease University of Alabama at Birmingham Birmingham (V.A.B.) Estudios Cardiológicos Latinoamérica Instituto Cardiovascular de Rosario Rosario Argentina (R.D.) Sanofi Bridgewater NJ (J.M.E. A.M. J.-F.T.) the Canadian VIGOUR Centre University of Alberta Edmonton and St. Michael’s Hospital University of Toronto Toronto — both in Canada (S.G.G.) Stanford Center for Clinical Research Department of Medicine Stanford University Stanford CA (R.A.H. K.W.M.) the Department of Cardiology Leiden University Medical Center Leiden the Netherlands (J.W.J.) Duke Clinical Research Institute Duke University Medical Center (K.Q. M.T.R. P.T.) and the Division of Cardiology Department of Medicine Duke University School of Medicine (M.T.R.) Durham NC Green Lane Cardiovascular Services Auckland City Hospital Auckland New Zealand (H.D.W.) and the Department of Medicine III Goethe University Frankfurt am Main Germany (A.M.Z.).

Background:Patients who have had an acute coronary syndrome are at high risk for recurrent ischemic cardiovascular *** sought to determine whether alirocumab,a human monoclonal antibody to proprotein convertase subtilisin-kexin type 9(PCSK9),would improve cardiovascular outcomes after an acute coronary syndrome in patients receiving high-intensity statin therapy.

关键词： cardiovascular acute coronary

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Characterization of a novel mouse model with genetic deletion of CD177

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Protein & Cell 2015年第2期6卷 117-126页

作者： Qing Xie Julia Klesney-Tait Kathy Keck Corey Parlet Nicholas Borcherding Ryan Kolb Wei Li Lorraine Tygrett Thomas Waldschmidt Alicia Olivier Songhai Chen Guang-Hui Liu Guang-Hui Liu Xiangrui Li Weizhou Zhang College of Veterinary Medicine Nanjing Agricultural University Nanjing 210095 China Department of Pathology Holden Comprehensive Cancer Center Carver College of Medicine/University of Iowa Iowa IA 52242 USA Department of Internal Medicine Carver College of Medicine/University of Iowa Iowa IA 52242 USA Department of Pharmacology Carver College of Medicine/University of Iowa Iowa IA 52242 USA National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China Beijing Institute for Brain Disorders Beijing 100069 China

Neutrophils play an essential role in the innate immune response to infection. Neutrophils migrate from the vasculature into the tissue in response to infection. Recently, a neutrophil cell surface receptor, CD177, was shown to help mediate neutrophil migration across the endothelium through interactions with PECAMI. We examined a publicly available gene array dataset of CD177 expression from human neutrophils following pulmonary endotoxin instillation. Among all 22,214 genes examined, CD177 mRNA was the most upregu- lated following endotoxin exposure. The high level of CD177 expression is also maintained in airspace neu- trophils, suggesting a potential involvement of CD177 in neutrophil infiltration under infectious diseases. To determine the role of CD177 in neutrophils in vivo, we constructed a CD177-genetic knockout mouse model. The mice with homozygous deletion of CD177 have no discernible phenotype and no significant change in immune cells, other than decreased neutrophil counts in peripheral blood. We examined the role of CD177 in neutrophil accumulation using a skin infection model with Staphylococcus aureus. CD177 deletion reducedneutrophil counts in inflammatory skin caused by S. aureus. Mechanistically we found that CD177 deletion in mouse neutrophils has no significant impact in CXCLI/ KC- or fMLP-induced migration, but led to significant cell death. Herein we established a novel genetic mouse model to study the role of CD177 and found that CD177 plays an important role in neutrophils.

关键词： CD177 neutrophil mouse model geneticdeletion

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