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Proteomics. Clinical Applications

Jiyeong Lee, Sora Mun, Doojin Kim, You-Rim Lee, Dong-Hyuk Sheen, Chunhwa Ihm, Seung Hoon Lee, Hee-Gyoo Kang
PURPOSE: Rheumatoid arthritis (RA) is an autoimmune disease in which autoantibodies attack the synovial membrane, causing joint inflammation. Blood tests would offer a powerful, minimally invasive method for early diagnosis of RA. However, no reliable biomarkers for RA are presently available. Our aim was to develop biomarkers for RA by multiple reaction monitoring (MRM)-based quantification of candidate biomarkers. EXPERIMENTAL DESIGN: Proteomics approaches are commonly used to identify and verify disease biomarkers...
September 19, 2018: Proteomics. Clinical Applications
Daniel Kazdal, Rémi Longuespée, Steffen Dietz, Rita Casadonte, Kristina Schwamborn, Anna-Lena Volckmar, Jörg Kriegsmann, Katharina Kriegsmann, Margaux Fresnais, Albrecht Stenzinger, Holger Sültmann, Arne Warth, Mark Kriegsmann
PURPOSE: Matrix assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI MSI) is a powerful tool to analyze the spatial distribution of peptides in tissues. Digital polymerase chain reaction (dPCR) is a method to reliably detect genetic mutations. Biopsy material is often limited due to minimally invasive techniques, but information on diagnosis, prognosis and prediction is required for subsequent clinical decision making. Thus, saving tissue material during diagnostic workup is highly warranted for best patient care...
September 14, 2018: Proteomics. Clinical Applications
Rémi Longuespée, Katharina Kriegsmann, Martin Cremer, Christiane Zgorzelski, Rita Casadonte, Daniel Kazdal, Jörg Kriegsmann, Wilko Weichert, Kristina Schwamborn, Margaux Fresnais, Peter Schirmacher, Mark Kriegsmann
BACKGROUND: In matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) standardized sample preparation is important to obtain reliable results. Herein, we investigated the impact of section thickness in formalin-fixed paraffin embedded (FFPE) tissue microarrays (TMA) on spectral intensities. PATIENTS AND METHODS: TMAs consisting of 10 different tissues represented by duplicates of 10 patients (n = 200 cores) were cut at 1, 3 and 5 μm...
September 14, 2018: Proteomics. Clinical Applications
Benjamin Chaigne, Guilhem Clary, Morgane Le Gall, Nicolas Dumoitier, Claire Fernandez, Sebastien Lofek, Philippe Chafey, Pia Moinzadeh, Thomas Krieg, Christopher P Denton, Luc Mouthon
PURPOSE: Systemic sclerosis (SSc) is characterized by autoimmunity, vasculopathy and fibrosis. Fibrosis is due to an activation of fibroblasts by the transforming growth factor-ß (TGF-ß). This study investigates the proteomic response of SSc fibroblasts to TGF-ß. EXPERIMENTAL DESIGN: Skin fibroblasts from diffuse SSc patients and healthy controls (HC) are cultured with or without TGF-ß. Two-dimensional differential in-gel electrophoresis and mass spectrometry (MS) combined with Ingenuity Pathway analysis (IPA) and Panther/David software analyze proteins differentially expressed between groups...
August 23, 2018: Proteomics. Clinical Applications
Saikat Paul, Pankaj Singh, Savitri Sharma, Gandham Satyanarayana Prasad, Shivaprakash Mandya Rudramurthy, Arunaloke Chakrabarti, Anup K Ghosh
PURPOSE: Invasive fungal infections caused by melanized fungi are a growing concern. Rapid and reliable identification plays an important role in optimizing therapy. Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) based identification has emerged as a faster and accurate diagnostic technique. However, lack of protein extraction protocol and limited database restricts the identification of melanized fungi by MALDI-TOF MS. This study was designed to standardize protein extraction protocol, to enrich the existing and to create an in-house database for the rapid identification of melanized fungi...
August 23, 2018: Proteomics. Clinical Applications
Klaus Kratochwill
Dialysis as renal replacement therapy, aims to remove excess water and waste solutes from the uremic patient while retaining proteins in the plasma. Irrespective of the dialysis modality, hemodialysis (HD) or peritoneal dialysis (PD), the amount and composition of proteins that are removed are important determinants of the biocompatibility of the therapy. Although hemodialysis membranes would ideally be biologically inert filtration tubes, they are known to adsorb proteins. The part of the plasma proteome that is thereby removed during every dialysis session may be regarded as the extracorporeal proteome which has to be kept in balance with the plasma proteome, regarding the individual proteins' biological roles and activation states...
August 23, 2018: Proteomics. Clinical Applications
Anna Drabik
Protein glycosylation, as one of the most common and complex posttranslational modifications, plays an important role in many biological processes. Along with the intensive progress in mass spectrometry techniques and development of glycan search tools and databases, glycoproteomics has become a popular subject of studies. The possibility of simultaneous identification of amino acid sequence, glycosylation sites, and glycan composition enabled the monitoring of changes in glycosylation patterns in various pathological states...
August 10, 2018: Proteomics. Clinical Applications
Charles Pottier, Mark Kriegsmann, Deborah Alberts, Nicolas Smargiasso, Dominique Baiwir, Gabriel Mazzucchelli, Michael Herfs, Margaux Fresnais, Rita Casadonte, Philippe Delvenne, Edwin De Pauw, Rémi Longuespée
PURPOSE: High-grade squamous intraepithelial lesion (HSIL) is a known precursor for squamous cell carcinoma of uterine cervix. Although it is known that SILs are associated to infection by human papillomavirus, downstream biological mechanisms are still poorly described. In this study, we compared the microproteomic profile of HSIL to normal tissues: ectocervix (ectoC) and endocervix (endoC). EXPERIMENTAL DESIGN: Tissue regions of endoC, ectoC, and HSlL were collected by laser microdissection (3500 cells each) from five patients...
August 10, 2018: Proteomics. Clinical Applications
Susanna Naggie, Meredith Clement, Sam Lusk, Anu Osinusi, Tiffany Himmel, Joseph E Lucas, Will J Thompson, Laura Dubois, M Arthur Moseley, Paul J Clark, Shyam Kottilil, Keyur Patel
PURPOSE: In the interferon era of hepatitis C virus (HCV) therapies, genotype/subtype, cirrhosis, prior treatment failure, sex, and race predicted relapse. Our objective is to validate a targeted proteomics platform of 17 peptides to predict sustained virologic response (SVR). EXPERIMENTAL DESIGN: Stored plasma from three, open-label, trials of HIV/HCV-coinfected subjects receiving interferon-containing regimens is identified. LC-MS/MS is used to quantitate the peptides directly from plasma, and IL28B genotyping is completed using stored peripheral blood mononuclear cells (PBMC)...
July 30, 2018: Proteomics. Clinical Applications
Amalia Conti, Alessandra Luchini, Maria Serena Benassi, Giovanna Magagnoli, Michela Pierini, Martina Piccinni-Leopardi, Irene Quattrini, Serena Pollino, Piero Picci, Lance A Liotta, Laura Pazzaglia
PURPOSE: Approximately 5% of giant cell tumors (GCT) of bone develop pulmonary metastases. Although many biomarkers have been proposed, identification of circulating low abundance molecules may be useful to predict malignant progression. EXPERIMENTAL DESIGN: The hydrogel nanoparticle technique followed by MS was used to detect low molecular weight serum proteins or protein fragments in serum of 20 GCT patients with different clinical course and in ten healthy sera used as control...
July 27, 2018: Proteomics. Clinical Applications
Katharina Kriegsmann, Rémi Longuespée, Michael Hundemer, Christiane Zgorzelski, Rita Casadonte, Kristina Schwamborn, Wilko Weichert, Peter Schirmacher, Alexander Harms, Daniel Kazdal, Jonas Leichsenring, Albrecht Stenzinger, Arne Warth, Margaux Fresnais, Jörg Kriegsmann, Mark Kriegsmann
OBJECTIVE: Tissue slides analyzed by MS imaging (MSI) are stained by H&E (Haematoxylin and Eosin) to identify regions of interest. As it can be difficult to identify specific cells of interest by H&E alone, data analysis may be impaired. Immunohistochemistry (IHC) can highlight cells of interest but single or combined IHC on tissue sections analyzed by MSI have not been performed. METHODS: We performed MSI on bone marrow biopsies from patients with multiple myeloma and stained different antibodies (CD38, CD138, MUM1, kappa- and lambda)...
July 23, 2018: Proteomics. Clinical Applications
Niannian Wang, Shu Zhang, Feifei Zhu, Yanhua Yang, Liang Chen, Peng Lü, Li Yu, Keping Chen
PURPOSE: Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia. So far, the pathogenesis of diabetes has not been fully elucidated. Identifying new potential molecule mechanisms and biomarkers in this process could contribute to the understanding of pathophysiology. EXPERIMENTAL DESIGN: Proteomic changes in the liver of type 2 diabetic mice (n = 6) and normal mice (n = 6) are studied. Triplicate experiments are carried out for each sample...
July 23, 2018: Proteomics. Clinical Applications
Xingyun Wang, Siliang Xu, Ling Chen, Dan Shen, Yan Cao, Ranran Tang, Xing Wang, Chenbo Ji, Yun Li, Xianwei Cui, Xirong Guo
PURPOSE: Peptide drugs provide promising regimes in anti-obesity treatment. In order to identify potential bioactive peptides involved in adipogenesis. EXPERIMENTAL DESIGN: The intracellular peptides between preadipocytes and adipocytes are compared by liquid chromatography/mass spectrometry. The underlying biological function of the identified peptides are evaluated by gene ontology (GO) and pathway analysis of their precursors. To find more potential bioactive peptides, 50 peptide sequences are identified located in the functional domains with the use of the SMART and UniProt databases...
July 16, 2018: Proteomics. Clinical Applications
Zheng Minghui, Hu Kunhua, Bao Yunwen, Lu Hongmei, Li Jing, Wu Shaowen, Sun Longqiaozi, Duan Chaohui
PURPOSE: In order to study the candidate biomarkers in autoimmune cirrhosis (AIC). EXPERIMENTAL DESIGN: Isobaric tags are first implemented for relative and absolute quantitation technology on proteins prepared from serum obtained from AIC and normal controls. Proteins found to be differentially expressed are identified with liquid chromatography electrospray ionization tandem mass spectrometry by using a Q Exactive classic ion trap mass spectrometer. RESULTS: 108 proteins (32 upregulated and 76 downregulated proteins) are identified from AIC samples, compared with the normal controls...
July 12, 2018: Proteomics. Clinical Applications
Mayank Saraswat, Antti Mäkitie, Tiialotta Tohmola, Amy Dickinson, Shruti Saraswat, Sakari Joenväärä, Suvi Renkonen
PURPOSE: There are no blood biomarkers to detect early-stage oral cavity squamous cell carcinoma (OSCC) prior to clinical signs. Most OSCC incidence is associated with significant morbidity and poor survival. The authors aimed to use mass-spectrometry (MS) technology to find specific N-glycopeptides potentially serving as serum biomarkers for preclinical OSCC screening. EXPERIMENTAL DESIGN: Serum samples from 14 patients treated for OSCC (stage I or stage IV) with 12 age- and sex-matched controls are collected...
July 11, 2018: Proteomics. Clinical Applications
Marcello Manfredi, Carmela Chiariello, Eleonora Conte, Annalisa Castagna, Elisa Robotti, Fabio Gosetti, Mauro Patrone, Nicola Martinelli, Antonella Bassi, Daniela Cecconi, Emilio Marengo, Oliviero Olivieri
PURPOSE: The present research reports the study the of plasma proteome profile of stable coronary artery disease (CAD) patients characterized by different levels of total Apolipoprotein-CIII (Apo C-III), a prognostic marker for cardiovascular risk. EXPERIMENTAL DESIGN: Two subgroups of CAD patients (n = 52) with divergent concentrations of total circulating Apo C-III (≤ and ≥10 mg dL-1 ) are examined using a shotgun proteomic approach. Validation experiments are also performed with immunochemistry methods including both the patients affected by CAD (n = 119) and the subjects without CAD (CAD-free; n = 58)...
July 10, 2018: Proteomics. Clinical Applications
Tadashi Kondo
Ewing's sarcoma is an extremely rare mesenchymal malignancy of the bone, which predominantly occurs in children and young adolescents. Ewing's sarcoma is characterized by chromosomal translocations resulting in the formation of chimeric fusions between the EWS gene and transcription factors of the ETS family, such as EWS-FLI-1. The clinical outcome of Ewing's sarcoma remains poor, and novel therapeutic approaches are required. Proteomic analyses have been applied to identify the functions of the fusion gene product, and a novel mechanism of EWS-FLI-1 turnover has been proposed...
July 10, 2018: Proteomics. Clinical Applications
Manja Wölter, Charles A Okai, Derek S Smith, Manuela Ruß, Werner Rath, Ulrich Pecks, Christoph H Borchers, Michael O Glocker
PURPOSE: Intrauterine growth restriction, a major cause of fetal morbidity and mortality, is defined as a condition in which the fetus does not reach its genetically given growth potential. Screening for intrauterine growth restriction biomarkers in the mother's blood would be of great help for optimal pregnancy management and timing of delivery as well as for identifying fetuses requiring further surveillance during their infancies. EXPERIMENTAL DESIGN: A multiplexing serological assay based on liquid chromatography-multiple-reaction-monitoring mass spectrometry is applied for distinguishing serum samples of pregnant women...
June 29, 2018: Proteomics. Clinical Applications
Domenica Scumaci, Antonio Oliva, Antonio Concolino, Antonio Curcio, Claudia Vincenza Fiumara, Laura Tammè, Oscar Campuzano, Vincenzo L Pascali, Monica Coll, Anna Iglesias, Paola Berne, Gavino Casu, Erika Olivo, Francesco Ausania, Pietrantonio Ricci, Ciro Indolfi, Josep Brugada, Ramon Brugada, Giovanni Cuda
PURPOSE: The Brugada syndrome (BrS) is a severe inherited cardiac disorder. Given the high genetic and phenotypic heterogeneity of this disease, three different "omics" approaches are integrated in a synergic way to elucidate the molecular mechanisms underlying the pathophysiology of BrS as well as for identifying reliable diagnostic/prognostic markers. EXPERIMENTAL DESIGN: The profiling of plasma Proteome and MiRNome is perfomed in a cohort of Brugada patients that were preliminary subjected to genomic analysis to assess a peculiar gene mutation profile...
June 28, 2018: Proteomics. Clinical Applications
Christine Eymann, Gerhild Wachlin, Dirk Albrecht, Stephan Tiede, Ulrike Krummrei, Michael Jünger, Michael Hecker, Georg Daeschlein
PURPOSE: Increasing incidence of onychomycosis and tinea pedis in humans of industrialized countries together with deep tissue infections are a therapeutic challenge in clinical mycology. For a better understanding of the pathology and immunology of infection, the authors analyze the exoproteomes of three reference strains of the most common clinical dermatophyte species (Trichophyton rubrum, Trichophyton interdigitale, Arthroderma benhamiae) and of Trichophyton strains isolated from affected patients...
June 28, 2018: Proteomics. Clinical Applications
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