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https://www.readbyqxmd.com/read/28730919/an-update-on-biomarker-discovery-and-use-in-systemic-sclerosis
#1
Takashi Matsushita, Kazuhiko Takehara
Systemic sclerosis (SSc) is an autoimmune disease characterized by excessive extracellular matrix deposition in the skin and internal organs. Three major abnormalities, autoimmunity, vasculopathy, and fibrosis, are considered to play important roles in the pathophysiology of SSc. SSc is a heterogeneous disease with clinical features, disease progress, therapeutic response, and prognosis. Therefore, identification of biomarkers, which can predict the course of the disease, is required for the progress of clinical practice...
July 21, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28730484/analysis-of-phosphotyrosine-signaling-networks-in-lung-cancer-cell-lines
#2
Malgorzata Broncel, Paul H Huang
Robust isolation and identification of peptides phosphorylated at their tyrosine residues are key steps in deciphering complex signaling networks governed by protein tyrosine kinases, including kinases involved in oncogenesis. Phosphotyrosine (pY)-containing peptides are commonly isolated from cellular lysates by means of antibody and/or metal affinity-based enrichment followed by their identification by mass spectrometry. Herein, we describe robust two-stage isolation of phosphotyrosine peptides and mass spectrometry-aided identification of phosphosites to characterize basal signaling networks in unstimulated non-small cell lung cancer (NSCLC) cell lines...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28729397/the-igf1r-insr-inhibitor-bi-885578-selectively-inhibits-growth-of-igf2-overexpressing-colorectal-cancer-tumors-and-potentiates-the-efficacy-of-anti-vegf-therapy
#3
Michael P Sanderson, Marco H Hofmann, Pilar Garin-Chesa, Norbert Schweifer, Andreas Wernitznig, Stefan Fischer, Astrid Jeschko, Reiner Meyer, Jurgen Moll, Thomas Pecina, Heribert Arnhof, Ulrike Weyer-Czernilofsky, Stephan K Zahn, Günther R Adolf, Norbert Kraut
Clinical studies of pharmacological agents targeting the insulin like growth factor (IGF) pathway in unselected cancer patients have so far demonstrated modest efficacy outcomes, with objective responses being rare. As such, the identification of selection biomarkers for enrichment of potential responders represents a high priority for future trials of these agents. Several reports have described high IGF2 expression in a subset of colorectal cancers (CRC), with focal IGF2 amplification being responsible for some of these cases...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28729364/tgf-%C3%AE-transforming-growth-factor-%C3%AE-signaling-protects-the-thoracic-and-abdominal-aorta-from-angiotensin-ii-induced-pathology-by-distinct-mechanisms
#4
Stoyan N Angelov, Jie Hong Hu, Hao Wei, Nathan Airhart, Minghui Shi, David A Dichek
OBJECTIVE: The role of TGF-β (transforming growth factor-β) signaling in abdominal aortic aneurysm (AAA) formation is controversial. Others reported that systemic blockade of TGF-β by neutralizing antibodies accelerated AAA development in angiotensin II-infused mice. This result is consistent with other studies suggesting that TGF-β signaling prevents AAA. Development of a therapy for AAA that exploits the protective actions of TGF-β would be facilitated by identification of the mechanisms through which TGF-β prevents AAA...
July 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28728879/identification-of-universal-diagnostic-peptide-candidates-for-neglected-tropical-diseases-caused-by-cestodes-through-the-integration-of-multi-genome-wide-analyses-and-immunoinformatic-predictions
#5
Sebastián Miles, Marco Navatta, Sylvia Dematteis, Gustavo Mourglia-Ettlin
Neglected tropical diseases caused by helminth infections currently affect millions of people worldwide. Among them, there are three tapeworm species of outstanding importance: Echinococcus granulosus, E. multilocularis, and Taenia solium, which are responsible for cystic echinococcosis, alveolar echinococcosis, and cysticercosis, respectively. Despite several attempts, there is still a need for an effective and low-cost serological diagnostic test that can be used in endemic countries. In the present work, we described an innovative bioinformatic workflow for a rational prediction of putative peptide candidates for one-step serological diagnosis of any of these infections...
July 17, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28728472/the-identification-of-interferon-%C3%AE-as-a-key-supportive-factor-for-retinal-differentiation-of-murine-mesenchymal-stem-cells
#6
Barbora Hermankova, Jan Kossl, Eliska Javorkova, Pavla Bohacova, Michaela Hajkova, Alena Zajicova, Magdalena Krulova, Vladimir Holan
Retinal disorders represent the main cause of decreased quality of vision and even blindness worldwide. The loss of retinal cells causes irreversible damage of the retina and there are currently no effective treatment protocols for most retinal degenerative diseases. A promising approach for the treatment of retinal disorders is represented by stem cell-based therapy. The perspective candidates are mesenchymal stem cells (MSCs) which can differentiate into multiple cell types and produce a number of trophic and growth factors...
July 20, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28727448/extensive-survey-of-antibody-invariant-positions-for-efficient-chemical-conjugation-using-expanded-genetic-codes
#7
Akifumi Kato, Mitsuo Kuratani, Tatsuo Yanagisawa, Kazumasa Ohtake, Akiko Hayashi, Yoshimi Amano, Kaname Kimura, Shigeyuki Yokoyama, Kensaku Sakamoto, Yasuhisa Shiraishi
The site-specific chemical conjugation of proteins, following synthesis with an expanded genetic code, promises to advance antibody-based technologies, including antibody drug conjugation and the creation of bispecific Fab dimers. The incorporation of non-natural amino acids into antibodies not only guarantees site specificity but also allows the use of bio-orthogonal chemistry. However, the efficiency of amino acid incorporation fluctuates significantly among different sites, thereby hampering the identification of useful conjugation sites...
July 20, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28726496/a-preclinical-study-in-rhesus-macaques-for-cystic-fibrosis-to-assess-gene-transfer-and-transduction-by-aav1-and-aav5-with-a-dual-luciferase-reporter-system
#8
William Guggino, Janet Benson, JeanClare Seagrave, Ziying Yan, John F Engelhardt, Guangping Gao, Thomas J Conlon, Liudmila Cebotaru
Cystic fibrosis (CF) is an autosomal recessive disease that is potentially treatable by gene therapy. Since the identification of the gene encoding CFTR, a number of preclinical and clinical trials have been conducted using the first generation of adeno-associated virus, AAV2. All these studies showed that AAV gene therapy for CF is safe, but clinical benefit was not clearly demonstrated. Thus, a new generation of AAV Vectors based on other serotypes is needed to move the field forward. Here we have tested two AAV serotypes (AAV1 and AAV5), using a dual-luciferase reporter system with firefly and Renilla luciferase genes packaged into AAV1 or AAV5, respectively...
July 20, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28726484/annals-express-experience-with-newer-central-nervous-system-autoantibodies
#9
Abid Karim, Saiju Jacob
In the last decade, a large number of neuronal cell-surface antibodies have been described which are responsible for a range of neuroimmunological central nervous system disorders. Unlike the paraneoplastic antibodies which target intracellular antigens, these antibodies appear to be pathogenic and hence identification and prompt treatment can make a substantial impact on clinical outcomes of these patients. We review the common antibodies against the ionotropic Glutamate receptors (NMDAR, AMPAR), metabotropic Glutamate receptors (mGluR1 and mGluR5), voltage gated potassium channel-complex proteins (LGI1, CASPR2), and other antibodies targeted against Glycine receptor, Glutamic acid decarboxylase (GAD), Gamma Amino Butyric Acid B (GABAB), Dopamine-2-receptor (D2R) and Dipeptidyl-peptidase-like protein 6 (DPPX)...
January 1, 2017: Annals of Clinical Biochemistry
https://www.readbyqxmd.com/read/28726418/quantitative-assessment-of-the-effects-of-trypsin-digestion-methods-on-affinity-purification-mass-spectrometry-based-protein-protein-interaction-analysis
#10
Yueqing Zhang, Hong Sun, Jing Zhang, Allan R Brasier, Yingxin Zhao
Affinity purification-mass spectrometry (AP-MS) has become the method of choice for discovering protein-protein interactions (PPIs) under native conditions. The success of AP-MS depends on the efficiency of trypsin digestion and the recovery of the tryptic peptides for MS analysis. Several different protocols have been used for trypsin digestion of protein complexes in AP-MS studies, but no systematic studies have been conducted on the impact of trypsin digestion conditions on the identification of PPIs. Here, we used NFκB/RelA and Bromodomain-containing protein 4 (BRD4) as baits and test five distinct trypsin digestion methods (two using "on-beads," three using "elution-digestion" protocols)...
July 20, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28723905/evolution-of-anti-trypanosoma-cruzi-antibody-production-in-patients-with-chronic-chagas-disease-correlation-between-antibody-titers-and-development-of-cardiac-disease-severity
#11
Ingebourg Georg, Alejandro Marcel Hasslocher-Moreno, Sergio Salles Xavier, Marcelo Teixeira de Holanda, Eric Henrique Roma, Maria da Gloria Bonecini-Almeida
Chagas disease is one of the most important endemic infections in Latin America affecting around 6-7 million people. About 30-50% of patients develop the cardiac form of the disease, which can lead to severe cardiac dysfunction and death. In this scenario, the identification of immunological markers of disease progression would be a valuable tool for early treatment and reduction of death rates. In this observational study, the production of anti-Trypanosoma cruzi antibodies through a retrospective longitudinal follow-up in chronic Chagas disease patients´ cohort and its correlation with disease progression and heart commitment was evaluated...
July 19, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28723416/unravelling-the-pharmacologic-opportunities-and-future-directions-for-targeted-therapies-in-gastro-intestinal-cancers-part-2-neuroendocrine-tumours-hepatocellular-carcinoma-and-gastro-intestinal-stromal-tumours
#12
REVIEW
Cindy Neuzillet, Louis de Mestier, Benoît Rousseau, Olivier Mir, Mohamed Hebbar, Hemant M Kocher, Philippe Ruszniewski, Christophe Tournigand
Until the 1990s, cytotoxic chemotherapy has been the cornerstone of medical therapy for gastrointestinal (GI) cancers. Better understanding of the cancer cell molecular biology has led to the therapeutic revolution of targeted therapies, i.e. monoclonal antibodies or small molecule inhibitors directed against proteins that are specifically overexpressed or mutated in cancer cells. These agents, being more specific to cancer cells, were expected to be less toxic than conventional cytotoxic agents. However, their effects have sometimes been disappointing, due to intrinsic or acquired resistance mechanisms, or to an activity restricted to some tumour settings, illustrating the importance of patient selection and early identification of predictive biomarkers of response to these therapies...
July 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28722619/evaluation-of-onchocerciasis-transmission-in-tanzania-preliminary-rapid-field-results-in-the-tukuyu-focus-2015
#13
Heather N Paulin, Andreas Nshala, Akili Kalinga, Upendo Mwingira, Ryan Wiegand, Vitaliano Cama, Paul T Cantey
To compare diagnostic tests for onchocerciasis in a setting that has suppressed transmission, a randomized, age-stratified study was implemented in an area in Tanzania that had received 15 rounds of annual mass drug administration (MDA) with ivermectin. Study participants (N = 948) from 11 villages underwent a questionnaire, skin examination, skin snips, and blood draw. The burden of symptomatic disease was low. Ov-16 antibody rapid diagnostic test (RDT) results were positive in 38 (5.5%) participants, with 1 (0...
June 12, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28722319/immunophenotypic-aberrancies-in-acute-lymphoblastic-leukemia-from-282-iraqi-patients
#14
S D Jalal, N A S Al-Allawi, A A S Al Doski
INTRODUCTION: The identification of aberrancies in leukemia-associated immunophenotype (LAIP) of acute lymphoblastic leukemia (ALL) is quite important in the assessment of minimal residual disease (MRD). This study, the first from Iraq, aimed to assess the frequency and patterns of LAIP among Iraqi patients with ALL, to establish future strategies for evaluating MRD. METHODS: A total of 282 newly diagnosed Iraqi ALL cases were analyzed with six-parameter flow cytometry using a panel of 29 monoclonal antibodies...
July 18, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28721629/epha3-targeting-reduces-in-vitro-adhesion-and-invasion-and-in-vivo-growth-and-angiogenesis-of-multiple-myeloma-cells
#15
Francesco La Rocca, Irma Airoldi, Emma Di Carlo, Pina Marotta, Geppino Falco, Vittorio Simeon, Ilaria Laurenzana, Stefania Trino, Luciana De Luca, Katia Todoerti, Oreste Villani, Martin Lackmann, Fiorella D'Auria, Francesco Frassoni, Antonino Neri, Luigi Del Vecchio, Pellegrino Musto, Daniela Cilloni, Antonella Caivano
PURPOSE: Multiple myeloma (MM) is a hematologic malignancy characterized by a clonal expansion of plasma cells (PCs) in the bone marrow (BM). Since MM has so far remained incurable, further insights into its pathogenesis and the concomitant identification of new therapeutic targets are urgently needed. The tyrosine kinase receptor EphA3 is known to be involved in various cellular processes including cell viability, cell movement and cell-cell interactions. Recently, EphA3 has emerged as a potential therapeutic target in several hematologic and solid tumors...
July 18, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28720870/monocyte-adhesion-to-atherosclerotic-matrix-proteins-is-enhanced-by-asn-gly-arg-deamidation
#16
Bamaprasad Dutta, Jung Eun Park, Subodh Kumar, Piliang Hao, Xavier Gallart-Palau, Aida Serra, Yan Ren, Vitaly Sorokin, Chuen Neng Lee, Hee Hwa Ho, Dominique de Kleijn, Siu Kwan Sze
Atherosclerosis arises from leukocyte infiltration and thickening of the artery walls and constitutes a major component of vascular disease pathology, but the molecular events underpinning this process are not fully understood. Proteins containing an Asn-Gly-Arg (NGR) motif readily undergo deamidation of asparagine to generate isoDGR structures that bind to integrin αvβ3 on circulating leukocytes. Here we report the identification of isoDGR motifs in human atherosclerotic plaque components including extracellular matrix (ECM) proteins fibronectin and tenascin C, which have been strongly implicated in human atherosclerosis...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28719950/isolation-and-characterization-of-vaccine-candidate-genes-including-csp-and-msp1-in-plasmodium-yoelii
#17
Seon-Hee Kim, Young-An Bae, Ju-Young Seoh, Hyun-Jong Yang
Malaria is an infectious disease affecting humans, which is transmitted by the bite of Anopheles mosquitoes harboring sporozoites of parasitic protozoans belonging to the genus Plasmodium. Despite past achievements to control the protozoan disease, malaria still remains a significant health threat up to now. In this study, we cloned and characterized the full-unit Plasmodium yoelii genes encoding merozoite surface protein 1 (MSP1), circumsporozoite protein (CSP), and Duffy-binding protein (DBP), each of which can be applied for investigations to obtain potent protective vaccines in the rodent malaria model, due to their specific expression patterns during the parasite life cycle...
June 2017: Korean Journal of Parasitology
https://www.readbyqxmd.com/read/28719914/the-significance-of-antibodies-against-domain-i-of-beta-2-glycoprotein-i-in-antiphospholipid-syndrome
#18
Hilde Kelchtermans, Walid Chayouâ, Bas de Laat
The antiphospholipid syndrome (APS) is characterized by vascular thrombosis and/or pregnancy morbidity with the persistent presence of antiphospholipid antibodies (aPLs). Progress is being made in understanding the pathogenesis of the syndrome, but difficulties persist in the identification of patients at risk for thrombosis and/or pregnancy morbidity. Beta-2 glycoprotein I (β2GPI), a plasma protein consisting of five sushi domains, is thought to be the main antigenic target of aPLs. Antibodies recognizing domain I of β2GPI are predominantly present in patients with an elevated risk of thrombosis, whereas antidomain IV/V antibodies are found in nonthrombotic autoimmune diseases...
July 18, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28719497/serologic-responses-in-childhood-pulmonary-tuberculosis
#19
Bareng A S Nonyane, Mark P Nicol, Nicholas J Andreas, Stefanie Rimmele, Nicole Schneiderhan-Marra, Lesley J Workman, Mark D Perkins, Thomas Joos, Tobias Broger, Jerrold J Ellner, David Alland, Beate Kampmann, Susan E Dorman, Heather J Zar
BACKGROUND: Identification of the Mycobacterium tuberculosis immunoproteome and antigens associated with serologic responses in adults has renewed interest in developing a serologic test for childhood tuberculosis (TB). We investigated IgG antibody responses against M. tuberculosis antigens in children with well-characterized TB. METHODS: We studied archived sera obtained from hospitalized children with suspected pulmonary TB, and classified as having confirmed TB (culture-confirmed), unlikely TB (clinical improvement without TB treatment), or unconfirmed TB (all others)...
July 15, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28718063/new-insights-on-platelets-and-platelet-derived-microparticles-in-systemic-lupus-erythematosus
#20
REVIEW
Marc Scherlinger, Vanja Sisirak, Christophe Richez, Estibaliz Lazaro, Pierre Duffau, Patrick Blanco
PURPOSE OF REVIEW: Current knowledge on the role of platelets and platelet-derived microparticles (PMPs) on the immune system has been fast-growing. Systemic lupus erythematosus (SLE) is a systemic auto-immune disorder characterized by a loss of tolerance toward nuclear auto-antigens. Although recent studies allowed a better understanding of SLE pathogenesis, there is an urgent need for the development of new treatments and the identification of new biomarkers to assess the disease activity...
August 2017: Current Rheumatology Reports
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