Identification of Differentially Expressed Circulating Exosomal
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Gene Expression, Network Analysis, and Drug Discovery of Neurofibromatosis Type 2-Associated Vestibular Schwannomas Based on Bioinformatics Analysis
Hindawi Journal of Oncology Volume 2020, Article ID 5976465, 9 pages https://doi.org/10.1155/2020/5976465 Research Article Gene Expression, Network Analysis, and Drug Discovery of Neurofibromatosis Type 2-Associated Vestibular Schwannomas Based on Bioinformatics Analysis Qiao Huang , Si-Jia Zhai , Xing-Wei Liao , Yu-Chao Liu, and Shi-Hua Yin Department of Otolaryngology & Head and Neck Surgery, e Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, China Correspondence should be addressed to Shi-Hua Yin; [email protected] Received 26 March 2020; Revised 27 May 2020; Accepted 1 June 2020; Published 15 July 2020 Academic Editor: Pierfrancesco Franco Copyright © 2020 Qiao Huang et al. ,is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Neurofibromatosis Type 2- (NF2-) associated vestibular schwannomas (VSs) are histologically benign tumors. ,is study aimed to determine disease-related genes, pathways, and potential therapeutic drugs associated with NF2-VSs using the bioinformatics method. Microarray data of GSE108524 were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were screened using GEO2R. ,e functional enrichment and pathway enrichment of DEGs were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes Genomes (KEGG). Furthermore, the STRING and Cytoscape were used to analyze the protein-protein interaction (PPI) network of all differentially expressed genes and identify hub genes. Finally, the enriched gene sets belonging to the identified pathways were queried against the Drug-Gene Interaction database to find drug candidates for topical use in NF2-associated VSs. -
Associations Between FCGR3A Polymorphisms and Susceptibility to Rheumatoid Arthritis: a Metaanalysis YOUNG HO LEE, JONG DAE JI, and GWAN GYU SONG
Associations Between FCGR3A Polymorphisms and Susceptibility to Rheumatoid Arthritis: A Metaanalysis YOUNG HO LEE, JONG DAE JI, and GWAN GYU SONG ABSTRACT. Objective. To investigate whether the Fcγ receptor (FCGR) polymorphism confers susceptibility to rheumatoid arthritis (RA). Methods. We conducted metaanalyses on the associations between FCGR polymorphisms and RA susceptibility as determined using (1) allele contrast, (2) recessive models, (3) dominant models, and (4) contrast of homozygotes, using fixed or random effects models. Results. A total of 10 separate comparisons were considered, which comprised 6 European and 4 Asian population samples. Metaanalysis of FCGR3A polymorphism revealed a significant associa- tion between the VV genotype and the risk of developing RA relative to the VF+FF genotype (OR 1.256, 95% CI 1.045–1.510, p = 0.015), with no evidence of between-study heterogeneity (p = 0.167). In subjects of European descent, a stronger association was observed between the VV geno- type and RA than for the FF genotype (OR 1.374, 95% CI 1.101–1.714, p = 0.005). In Asians, no such association was found. Metaanalysis of the VV vs FF genotype revealed a significantly increased OR in Europeans (OR 1.399, 95% CI 1.107–1.769, p = 0.005), but not in Asians. No asso- ciation was found between RA and the FCGR2A and FCGR3B polymorphisms in all subjects and in European and Asian populations, except for the NA22 vs NA11 of FCGR3B in Europeans. Conclusion. No relation was found between the FCGR2A polymorphism and susceptibility to RA in Europeans or Asians. The FCGR3A polymorphism was found to be associated with RA in Europeans but not in Asians. -
Single‑Nucleotide Polymorphisms and Copy Number Variations of the FCGR2A and FCGR3A Genes in Healthy Japanese Subjects
BIOMEDICAL REPORTS 2: 265-269, 2014 Single‑nucleotide polymorphisms and copy number variations of the FCGR2A and FCGR3A genes in healthy Japanese subjects HIROYUKI MORIYA1, KATSUHIKO SAITO1,2, NUALA HELSBY3, NAOMI HAYASHI1, SHIGEKAZU SUGINO4, MICHIAKI YAMAKAGE4, TAKERU SAWAGUCHI5, MASAHIKO TAKASAKI5, MASATO TAKAHASHI6 and NAHOKO KUROSAWA1 1Department of Pharmacy, Hokkaido Pharmaceutical University School of Pharmacy, Otaru, Hokkaido 047-0264; 2Department of Pharmacy, Sapporo Hokuyu Hospital, Sapporo, Hokkaido 003-0006, Japan; 3Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1142, New Zealand; 4Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido 060-8543; Departments of 5Pharmacy and 6Breast Surgery, National Hospital Organization Hokkaido Cancer Center, Sapporo, Hokkaido 003-0804, Japan Received October 24, 2013; Accepted November 18, 2013 DOI: 10.3892/br.2013.210 Abstract. FcγRII and FcγRIII are low-affinity Fcγ recep- previous findings regarding FCGR2A and FCGR3A alleles and tors that are encoded by the FCGR2A and FCGR3A genes, CNVs. These assays may provide a basis for the investigation of respectively. These genes contain functional single-nucleotide the role of these genes in the efficacy of antibody-based drugs, polymorphisms (SNPs), which alter the binding affinities of such as trastuzumab and rituximab, in Japanese subjects. these receptors for the γ chain of the Fc fragment of immu- noglobulin G. The known SNPs in FCGR2A and FCGR3A Introduction are rs1801274 (A>G; H131R) and rs396991 (T>G; F158V), respectively. It is also known that there are copy number varia- Fcγ receptors (FcγRs) bind specifically to the γ chain of the tions (CNVs) in the genetic locus (1q23) where FCGR2A and Fc fragment of immunoglobulin G (IgG) and are located on the FCGR3A are located. -
Integrated Weighted Gene Co-Expression Network Analysis Identi Ed That TLR2 and CD40 Are Related to Coronary Artery Disease
Integrated weighted gene co-expression network analysis identied that TLR2 and CD40 are related to coronary artery disease Bin Qi Liuzhou People's Hospital Jian-Hong Chen Liuzhou People's Hospital Lin Tao Liuzhou People's Hospital Chuan-Meng Zhu Liuzhou People's Hospital Yong Wang Liuzhou People's Hospital Guo-Xiong Deng The First People's of Nanning Liu Miao ( [email protected] ) LiuZhou People's Hospital https://orcid.org/0000-0001-6642-7005 Research article Keywords: Gene Expression Omnibus, Integrated weighted gene co-expression network analysis (WGCNA), Functional enrichment, Functional validation and prognostic analysis. Posted Date: October 7th, 2020 DOI: https://doi.org/10.21203/rs.3.rs-86115/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/16 Abstract Background: The current research attempted to identify possible hub genes and pathways of coronary artery disease (CAD) and to detect the possible mechanisms. Methods: Array data from GSE90074 were downloaded from the Gene Expression Omnibus (GEO) database. Integrated weighted gene co-expression network analysis (WGCNA) was performed to analyze the gene module and clinical characteristics. Gene Ontology annotation, Disease Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by clusterProler and the DOSE package in R. A protein-protein interaction (PPI) network was established using Cytoscape software, and signicant modules were analyzed using Molecular Complex Detection to identify hub genes. Then, further functional validation of hub genes in other microarrays and population samples was performed, and survival analysis was performed to investigate the prognosis. -
First Infusion Reactions Are Mediated by Fcγriiib and Neutrophils
Pharm Res (2018) 35: 169 https://doi.org/10.1007/s11095-018-2448-8 RESEARCH PAPER First Infusion Reactions are Mediated by FcγRIIIb and Neutrophils Felix Weber 1 & Daniel Breustedt 1,2 & Sonja Schlicht 3 & Claas A. Meyer 3 & Jens Niewoehner 4 & Martin Ebeling 1 & Per-Ola Freskgard5 & Peter Bruenker6 & Thomas Singer1 & Michael Reth7 & Antonio Iglesias1 Received: 29 March 2018 /Accepted: 15 June 2018 /Published online: 27 June 2018 # The Author(s) 2018 ABSTRACT FIR. FcγRIIIb-mediated FIR was abolished by depleting neu- Purpose Administration of therapeutic monoclonal antibod- trophils or blocking FcγRIIIb with CD11b antibodies. ies (mAbs) is frequently accompanied by severe first infusion Conclusions Human FcγRIIIb and neutrophils are primarily reactions (FIR). The mechanism driving FIR is still unclear. responsible for triggering FIR. Clinical strategies to prevent This study aimed to investigate the cellular and molecular FIR in patients should focus on this pathway and may include mechanisms causing FIR in humanized mouse models and transient depletion of neutrophils or blocking FcγRIIIb with their potential for evaluating FIR risk in patients. specific mAbs. Methods Mice humanized for Fc gamma receptors (FcγRs) were generated by recombination-mediated genomic replace- KEY WORDS human FcγRIIIb . humanized mouse model . ment. Body temperature, cytokine release and reactive oxygen immunotoxicology . infusion reactions . neutrophils species (ROS) were measured to assess FIR to mAbs. Results Infusion of human mAb specific for mouse transferrin receptor (HamTfR) into FcγR-humanized mice, produced marked transient hypothermia accompanied by an increase ABBREVIATIONS in inflammatory cytokines KC and MIP-2, and ROS. FIR ADA Anti-drug antibodies were dependent on administration route and Fc-triggered ef- ADCC Antibody-dependent cellular cytotoxicity fector functions mediated by neutrophils. -
Type of the Paper (Article
Supplementary figures and tables E g r 1 F g f2 F g f7 1 0 * 5 1 0 * * e e e * g g g * n n n * a a a 8 4 * 8 h h h * c c c d d d * l l l o o o * f f f * n n n o o o 6 3 6 i i i s s s s s s e e e r r r p p p x x x e e e 4 2 4 e e e n n n e e e g g g e e e v v v i i i t t t 2 1 2 a a a l l l e e e R R R 0 0 0 c o n tro l u n in fla m e d in fla m e d c o n tro l u n in fla m e d in fla m e d c o n tro l u n in fla m e d in fla m e d J a k 2 N o tc h 2 H if1 * 3 4 6 * * * e e e g g g n n n a a * * a * h h * h c c c 3 * d d * d l l l * o o o f f 2 f 4 n n n o o o i i i s s s s s s e e e r r 2 r p p p x x x e e e e e e n n n e e 1 e 2 g g g e e 1 e v v v i i i t t t a a a l l l e e e R R R 0 0 0 c o n tro l u n in fla m e d in fla m e d c o n tro l u n in fla m e d in fla m e d c o n tro l u n in fla m e d in fla m e d Z e b 2 C d h 1 S n a i1 * * 7 1 .5 4 * * e e e g g g 6 n n n * a a a * h h h c c c 3 * d d d l l l 5 o o o f f f 1 .0 * n n n * o o o i i i 4 * s s s s s s e e e r r r 2 p p p x x x 3 e e e e e e n n n e e e 0 .5 g g g 2 e e e 1 v v v i i i t t t a a a * l l l e e e 1 * R R R 0 0 .0 0 c o n tro l u n in fla m e d in fla m e d c o n tro l u n in fla m e d in fla m e d c o n tro l u n in fla m e d in fla m e d M m p 9 L o x V im 2 0 0 2 0 8 * * * e e e * g g g 1 5 0 * n n n * a a a * h h h * c c c 1 5 * 6 d d d l l l 1 0 0 o o o f f f n n n o o o i i i 5 0 s s s s s s * e e e r r r 1 0 4 3 0 p p p * x x x e e e * e e e n n n e e e 2 0 g g g e e e 5 2 v v v i i i t t t a a a l l l 1 0 e e e R R R 0 0 0 c o n tro l u n in fla m e d in fla m e d c o n tro l u n in fla m e d in fla m e d c o n tro l u n in fla m e d in fla m e d Supplementary Figure 1. -
Development and Validation of a Protein-Based Risk Score for Cardiovascular Outcomes Among Patients with Stable Coronary Heart Disease
Supplementary Online Content Ganz P, Heidecker B, Hveem K, et al. Development and validation of a protein-based risk score for cardiovascular outcomes among patients with stable coronary heart disease. JAMA. doi: 10.1001/jama.2016.5951 eTable 1. List of 1130 Proteins Measured by Somalogic’s Modified Aptamer-Based Proteomic Assay eTable 2. Coefficients for Weibull Recalibration Model Applied to 9-Protein Model eFigure 1. Median Protein Levels in Derivation and Validation Cohort eTable 3. Coefficients for the Recalibration Model Applied to Refit Framingham eFigure 2. Calibration Plots for the Refit Framingham Model eTable 4. List of 200 Proteins Associated With the Risk of MI, Stroke, Heart Failure, and Death eFigure 3. Hazard Ratios of Lasso Selected Proteins for Primary End Point of MI, Stroke, Heart Failure, and Death eFigure 4. 9-Protein Prognostic Model Hazard Ratios Adjusted for Framingham Variables eFigure 5. 9-Protein Risk Scores by Event Type This supplementary material has been provided by the authors to give readers additional information about their work. Downloaded From: https://jamanetwork.com/ on 10/02/2021 Supplemental Material Table of Contents 1 Study Design and Data Processing ......................................................................................................... 3 2 Table of 1130 Proteins Measured .......................................................................................................... 4 3 Variable Selection and Statistical Modeling ........................................................................................ -
Arming Tumor-Associated Macrophages to Reverse Epithelial
Published OnlineFirst August 15, 2019; DOI: 10.1158/0008-5472.CAN-19-1246 Cancer Tumor Biology and Immunology Research Arming Tumor-Associated Macrophages to Reverse Epithelial Cancer Progression Hiromi I.Wettersten1,2,3, Sara M.Weis1,2,3, Paulina Pathria1,2,Tami Von Schalscha1,2,3, Toshiyuki Minami1,2,3, Judith A. Varner1,2, and David A. Cheresh1,2,3 Abstract Tumor-associated macrophages (TAM) are highly expressed it engaged macrophages but not natural killer (NK) cells to within the tumor microenvironment of a wide range of cancers, induce antibody-dependent cellular cytotoxicity (ADCC) of where they exert a protumor phenotype by promoting tumor avb3-expressing tumor cells despite their expression of the cell growth and suppressing antitumor immune function. CD47 "don't eat me" signal. In contrast to strategies designed Here, we show that TAM accumulation in human and mouse to eliminate TAMs, these findings suggest that anti-avb3 tumors correlates with tumor cell expression of integrin avb3, represents a promising immunotherapeutic approach to redi- a known driver of epithelial cancer progression and drug rect TAMs to serve as tumor killers for late-stage or drug- resistance. A monoclonal antibody targeting avb3 (LM609) resistant cancers. exploited the coenrichment of avb3 and TAMs to not only eradicate highly aggressive drug-resistant human lung and Significance: Therapeutic antibodies are commonly engi- pancreas cancers in mice, but also to prevent the emergence neered to optimize engagement of NK cells as effectors. In of circulating tumor cells. Importantly, this antitumor activity contrast, LM609 targets avb3 to suppress tumor progression in mice was eliminated following macrophage depletion. -
FCGR3B Polymorphism in Three Ethnic Chinese Populations
FCGR3B polymorphism in three ethnic Chinese populations L.YAN,F.ZHU,L.JIN,Q.LV,AND Q. FU 4,5,6 FcγRIIIb receptor is expressed primarily on neutrophils as three prevalent FCGR3B allele, whereas in certain polymorphic antigens (HNA-1a, HNA-1b, and HNA-1c) that are Chinese and Japanese populations, FCGR3B*1 is more encoded by alleles FCGR3B*1, FCGR3B*2, and FCGR3B*3, 7,8 respectively. These antigens play an important role in immune prevalent. FCGR3B*3 occurs in 0.05 percent of neutropenia; their absence predisposes individuals who lack them Caucasians,3 but has not been reported in Asians.7,8 to life-threatening infections. This study investigated the FCGR3B Rarely, individuals lack FcγRIIIb neutrophil antigens gene frequencies in three ethnic Chinese populations:Han,She,and (NA ), predisposing them to life-threatening Tajik. FCGR3B*1, FCGR3B*2, and FCGR3B*3 were genotyped by null PCR using sequence specific primers (PCR-SSP). The results infections. Also, several low-prevalence FCGR3B showed the gene frequencies were 0.55 for FCGR3B*1 and 0.45 for variant alleles that carry a single-base substitution of FCGR3B*2 in 177 Han individuals,0.69 for FCGR3B*1 and 0.31 for one of the five polymorphic sites on FCGR3B have FCGR3B*2 in 87 She individuals, and 0.35 for FCGR3B*1 and 0.65 been identified in certain Caucasian and Black for FCGR3B*2 in 99 Tajik individuals, respectively. The FCGR3Bnull genotype was not found, but the FCGR3B*3 allele was identified in populations.5,9 only three individuals in the Tajik population. -
Mouse and Human Fcr Effector Functions
Pierre Bruhns Mouse and human FcR effector € Friederike Jonsson functions Authors’ addresses Summary: Mouse and human FcRs have been a major focus of Pierre Bruhns1,2, Friederike J€onsson1,2 attention not only of the scientific community, through the cloning 1Unite des Anticorps en Therapie et Pathologie, and characterization of novel receptors, and of the medical commu- Departement d’Immunologie, Institut Pasteur, Paris, nity, through the identification of polymorphisms and linkage to France. disease but also of the pharmaceutical community, through the iden- 2INSERM, U760, Paris, France. tification of FcRs as targets for therapy or engineering of Fc domains for the generation of enhanced therapeutic antibodies. The Correspondence to: availability of knockout mouse lines for every single mouse FcR, of Pierre Bruhns multiple or cell-specific—‘a la carte’—FcR knockouts and the Unite des Anticorps en Therapie et Pathologie increasing generation of hFcR transgenics enable powerful in vivo Departement d’Immunologie approaches for the study of mouse and human FcR biology. Institut Pasteur This review will present the landscape of the current FcR family, 25 rue du Docteur Roux their effector functions and the in vivo models at hand to study 75015 Paris, France them. These in vivo models were recently instrumental in re-defining Tel.: +33145688629 the properties and effector functions of FcRs that had been over- e-mail: [email protected] looked or discarded from previous analyses. A particular focus will be made on the (mis)concepts on the role of high-affinity Acknowledgements IgG receptors in vivo and on results from antibody engineering We thank our colleagues for advice: Ulrich Blank & Renato to enhance or abrogate antibody effector functions mediated by Monteiro (FacultedeMedecine Site X. -
Engineered Type 1 Regulatory T Cells Designed for Clinical Use Kill Primary
ARTICLE Acute Myeloid Leukemia Engineered type 1 regulatory T cells designed Ferrata Storti Foundation for clinical use kill primary pediatric acute myeloid leukemia cells Brandon Cieniewicz,1* Molly Javier Uyeda,1,2* Ping (Pauline) Chen,1 Ece Canan Sayitoglu,1 Jeffrey Mao-Hwa Liu,1 Grazia Andolfi,3 Katharine Greenthal,1 Alice Bertaina,1,4 Silvia Gregori,3 Rosa Bacchetta,1,4 Norman James Lacayo,1 Alma-Martina Cepika1,4# and Maria Grazia Roncarolo1,2,4# Haematologica 2021 Volume 106(10):2588-2597 1Department of Pediatrics, Division of Stem Cell Transplantation and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA; 2Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA; 3San Raffaele Telethon Institute for Gene Therapy, Milan, Italy and 4Center for Definitive and Curative Medicine, Stanford School of Medicine, Stanford, CA, USA *BC and MJU contributed equally as co-first authors #AMC and MGR contributed equally as co-senior authors ABSTRACT ype 1 regulatory (Tr1) T cells induced by enforced expression of interleukin-10 (LV-10) are being developed as a novel treatment for Tchemotherapy-resistant myeloid leukemias. In vivo, LV-10 cells do not cause graft-versus-host disease while mediating graft-versus-leukemia effect against adult acute myeloid leukemia (AML). Since pediatric AML (pAML) and adult AML are different on a genetic and epigenetic level, we investigate herein whether LV-10 cells also efficiently kill pAML cells. We show that the majority of primary pAML are killed by LV-10 cells, with different levels of sensitivity to killing. Transcriptionally, pAML sensitive to LV-10 killing expressed a myeloid maturation signature. -
Context-Specific Regulation of Monocyte Surface IL7R Expression And
bioRxiv preprint doi: https://doi.org/10.1101/262410; this version posted July 15, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Context-specific regulation of monocyte surface IL7R expression and soluble receptor secretion by a common autoimmune risk allele Hussein Al-Mossawi2, Nicole Yager2, Chelsea Taylor1, Evelyn Lau3, Sara Danielli1, Jelle de Wit2, James Gilchrist3, Isar Nassiri1, Elise A Mahe1, Wanseon Lee3, Laila Rizvi2, Seiko Makino3, Jane Cheeseman4, Matt Neville4, Julian C Knight3¶, Paul Bowness2¶, Benjamin P Fairfax1¶* ¶ joint senior authors, *corresponding author 1Department of Oncology, MRC Weatherall Institute of Molecular Medicine; 2Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences; 3Nuffield Department of Medicine, Wellcome Centre for Human Genetics; 4Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom. Abstract IL-7 is a key factor in T-cell immunity and IL7R polymorphisms are implicated in autoimmune pathogenesis. IL7R mRNA is induced in stimulated monocytes in a genetically determined manner, yet a role for IL7R in monocyte biology remains unexplored. Here we characterize genetic regulation of IL7R at the protein level across multiple cell subsets and conditions in healthy individuals. We find monocyte surface and soluble IL7R (sIL7R) protein are markedly expressed in response to lipopolysaccharide (LPS). We further demonstrate alleles of rs6897932, a non-synonymous IL7R polymorphism associated with susceptibility to Multiple Sclerosis, Ankylosing Spondylitis and Primary Biliary Cirrhosis, form the key determinant of both surface IL7R and sIL7R in the context of inflammation.