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Proteomics. Clinical Applications

Emily M DeBoer, Brandie D Wagner, Jonathan Popler, J Kirk Harris, Edith T Zemanick, Frank J Accurso, Scott D Sagel, Robin R Deterding
PURPOSE: Biomarkers are needed in cystic fibrosis (CF) to understand disease progression, assess response to therapy, and enrich enrollment for clinical trials. Aptamer-based proteomics have proven useful in blood samples. We aimed to evaluate proteins in bronchoalveolar lavage fluid (BALF) in CF children compared to controls and identify endotypes during CF exacerbations. EXPERIMENTAL DESIGN: BALF was collected clinically from 50 patients with CF and 9 disease controls, processed, and stored per protocol...
November 15, 2018: Proteomics. Clinical Applications
Coşkun Güzel, Caroline B van den Berg, Johannes J Duvekot, Christoph Stingl, Thierry P P van den Bosch, Marcel van der Weiden, Eric A P Steegers, Regine P M Steegers-Theunissen, Theo M Luider
PURPOSE: The objective of present study was to determine serum levels and placental distribution of two interacting proteins calcyclin and heat shock protein 90 in preeclampsia. EXPERIMENTAL DESIGN: Maternal serum levels of calcyclin and heat shock protein 90 were compared throughout pregnancy from the first trimester till term among women with preeclampsia (n = 43) and age-matched normotensive pregnant controls (n = 46). A serum based 2D LC-MS assay using Parallel Reaction Monitoring was applied to quantify both calcyclin and heat shock protein 90...
November 11, 2018: Proteomics. Clinical Applications
Isabella Piga, Giulia Capitoli, Silvia Tettamanti, Vanna Denti, Andrew Smith, Clizia Chinello, Martina Stella, Davide Leni, Mattia Garancini, Stefania Galimberti, Fulvio Magni, Fabio Pagni
Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is an emerging technology which enables the spatial distribution of biomolecules within tissue to be combined with the traditional morphological information familiar to clinicians. Thus, for diagnostic, or prognostic purposes, along with predicting response to therapeutic treatment, it is important to properly collect and handle biological specimens in order to avoid degradation or the formation of artefacts in the morphological structure and proteomic profile...
November 9, 2018: Proteomics. Clinical Applications
Franziska Hoffmann, Claudia Umbreit, Thomas Krüger, Daniela Pelzel, Günther Ernst, Olaf Kniemeyer, Orlando Guntinas-Lichius, Alexander Berndt, Ferdinand von Eggeling
PURPOSE: The heterogeneity of squamous cell carcinoma tissue greatly complicates diagnosis and individualized therapy. Therefore, characterizing the heterogeneity of tissue spatially and identifying appropriate biomarkers is crucial. MALDI imaging (MSI) is capable of analyzing spatially resolved tissue biopsies on a molecular level. EXPERIMENTAL DESIGN: We used MALDI MSI on snap frozen and formalin-fixed and paraffin-embedded (FFPE) tissue samples from patients with head and neck cancer (HNC) to analyze m/z values localized in tumor and non-tumor regions...
November 9, 2018: Proteomics. Clinical Applications
Chao Xuan, Hui Li, Le-Le Li, Qing-Wu Tian, Qing Wang, Bei-Bei Zhang, Jun-Jie Guo, Guo-Wei He, Li-Min Lun
PURPOSE: The present study aimed to discover novel serum biomarkers of early-onset myocardial infarction (MI) using proteomic analysis. EXPERIMENTAL DESIGN: In the first stage, we utilized the iTRAQ-coupled LC-MS/MS technique to investigate protein profiles of patients with early-onset MI. In the second stage, we validated these candidate proteins using ELISA. RESULTS: 538 proteins were quantified, with pregnancy zone protein (PZP), leucine-rich alpha-2-glycoprotein (LRG) and Apolipoprotein C-I (Apo C-I) being up-regulated and Apolipoprotein A-I (Apo A-I) and Apolipoprotein A-IV (Apo A-IV) down-regulated in early-onset MI patients...
November 8, 2018: Proteomics. Clinical Applications
Alice Ly, Rémi Longuespée, Rita Casadonte, Petra Wandernoth, Kristina Schwamborn, Christine Bollwein, Christian Marsching, Katharina Kriegsmann, Carsten Hopf, Wilko Weichert, Jörg Kriegsmann, Peter Schirmacher, Mark Kriegsmann, Sören-Oliver Deininger
PURPOSE: To facilitate the transition of MALDI-MS Imaging (MALDI-MSI) from basic science to clinical application, it is necessary to analyze formalin-fixed paraffin-embedded (FFPE) tissues. Our aim was to improve in-situ tryptic digestion for MALDI-MSI of FFPE samples and determine if similar results would be reproducible if obtained from different sites. EXPERIMENTAL DESIGN: FFPE tissues (mouse intestine, human ovarian teratoma, tissue microarray of tumor entities sampled from three different sites) were prepared for MALDI-MSI...
November 8, 2018: Proteomics. Clinical Applications
Venkatraman Anandalakshmi, Guillaume Hochart, David Bonnel, Jonathan Stauber, Shigeto Shimmura, Rajamani Lakshminaryanan, Konstantin Pervushin, Jodhbir S Mehta
Corneal Dystrophies (CD) constitute a group of genetically inherited protein aggregation disorders that affect different layers of the cornea. With accumulated protein deposition, the cornea becomes opaque with decreased visual acuity. CD affecting the stroma and Bowman's membrane is associated with mutations in transforming growth factor β-induced (TGFBI) gene. The purpose of this study was to identify and visualize the spatial distribution of proteins present in amyloid corneal deposits of TGFBI-CD patients using Mass Spectrometry Imaging (MSI) and compare it with healthy control cornea...
November 2, 2018: Proteomics. Clinical Applications
Domenico Taverna, Chiara Mignogna, Gianluca Santise, Marco Gaspari, Giovanni Cuda
PURPOSE: The application of a methodology for quantitative protein analysis from FFPE tissue by using hydrogels. Miniaturized polymeric gels were placed onto histologically defined tissue regions in order to perform localized digestion for bottom-up proteomics. Hydrogel-extracted peptides were then labeled with tandem mass tags (TMT) reagents for relative protein quantification. A cardiac myxoma biopsy was used. EXPERIMENTAL DESIGN: Multiple hydrogels, incorporating the proteolytic enzyme trypsin, were placed on serial tissue sections, and processed for digestion and TMT derivatization...
November 2, 2018: Proteomics. Clinical Applications
Matthew T Briggs, Mark R Condina, Manuela Klingler-Hoffmann, Georgia Arentz, Arun V Everest-Dass, Gurjeet Kaur, Martin K Oehler, Nicolle H Packer, Peter Hoffmann
Protein glycosylation, particularly N-linked glycosylation, is a complex post-translational modification (PTM), which plays an important role in protein folding and conformation, regulating protein stability and activity, cell-cell interaction, and cell signalling pathways. This review focuses on analytical techniques, primarily mass spectrometry-based techniques, to qualitatively and quantitatively assess N-glycosylation while successfully characterising compositional, structural and linkage features with high specificity and sensitivity...
October 27, 2018: Proteomics. Clinical Applications
Yi Zhu, Jiang Zhu, Cong Lu, Qiushi Zhang, Wei Xie, Ping Sun, Xiaochuan Dong, Liang Yue, Yaoting Sun, Xiao Yi, Tiansheng Zhu, Guan Ruan, Ruedi Aebersold, Shi'ang Huang, Tiannan Guo
PURPOSE: To rapidly identify protein abundance changes in biopsy-level fresh-frozen hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: We applied the pressure-cycling technology (PCT) and optimized sequential window acquisition of all theoretical mass spectra (SWATH-MS) workflow to analyze 38 biopsy-level tissue samples from 19 HCC patients. Each proteome was analyzed with 45 min liquid chromatography (LC) gradient. MCM7 was validated using immunohistochemistry (IHC)...
October 26, 2018: Proteomics. Clinical Applications
Vincenzo L'Imperio, Andrew Smith, Elena Ajello, Isabella Piga, Martina Stella, Vanna Denti, Silvia Tettamanti, Renato Alberto Sinico, Federico Pieruzzi, Maurizio Garozzo, Gisella Vischini, Manuela Nebuloni, Fabio Pagni, Fulvio Magni
Membranous Nephropathy (MN) is the most frequent cause of nephrotic syndrome in adults and the disease course is characterised by the "rule of third", with one third of patients experiencing complete remission and the remaining experiencing relapses or progression of the disease. Additionally, the therapeutic approach is not standardised, leading to further heterogeneity in terms of response and outcome. In this pilot study, MALDI-MSI analysis was performed on renal biopsies (n = 13) obtained from two homogeneous groups of patients which differentially responded to the immunosuppressive treatments (Ponticelli regimen)...
October 25, 2018: Proteomics. Clinical Applications
Iwona Belczacka, Martin Pejchinovski, Magdalena Krochmal, Pedro Magalhães, Maria Frantzi, William Mullen, Antonia Vlahou, Harald Mischak, Vera Jankowski
PURPOSE: Urine is a rich source of potential biomarkers, including glycoproteins. Glycoproteomic analysis remains difficult due to the high heterogeneity of glycans. Nevertheless, recent advances in glycoproteomics software solutions facilitate glycopeptide identification and characterization. The aim is to investigate intact glycopeptides in the urinary peptide profiles of normal subjects using a novel PTM-centric software-Byonic. EXPERIMENTAL DESIGN: The urinary peptide profiles of 238 normal subjects, previously analyzed using CE-MS and CE-MS/MS and/or LC-MS/MS, are subjected to glycopeptide analysis...
October 18, 2018: Proteomics. Clinical Applications
Julie Klein, Joost P Schanstra
Preclinical animal models are extensively used in nephrology. In this review we have assessed the utility of performing proteome analysis of kidney tissue or urine in such models and transfer of the results to human application. Analysis of the literature identified 68 relevant publications. Pathway analysis of the reported proteins clearly indicated links with known biological processes in kidney disease providing validation of the observed changes in the preclinical models. However, we found that although most studies focused on the identification of early markers of kidney disease or prediction of its progression, none of the identified makers has made it to substantial validation in the clinic or at least in human samples...
October 18, 2018: Proteomics. Clinical Applications
Paulina B Szklanna, Martin E Parsons, Kieran Wynne, Hugh O'Connor, Karl Egan, Seamus Allen, Fionnuala Ní Áinle, Patricia B Maguire
PURPOSE: Healthy pregnancy is characterized by an increase in platelet activation and a decrease in the number of circulating platelets with gestation. Despite this recognized importance, proteomic studies investigating platelets in healthy pregnancy have not been performed. As platelet cargo can be altered in different conditions, it is hypothesized that platelets may store a relevant and bespoke collection of molecules during pregnancy. EXPERIMENTAL DESIGN: Comparative label-free quantitative proteomic profiling of platelet releasates (PRs) is performed from 18 healthy pregnant and 13 non-pregnant women using an MS/MS approach...
October 14, 2018: Proteomics. Clinical Applications
Kristina Schwamborn, Gregor Weirich, Katja Steiger, Gregor Zimmermann, Monika Schmidmayr, Wilko Weichert, Richard M Caprioli
PURPOSE: Malignant effusions challenge diagnostic accuracy due to cytomorphologic overlaps between various malignant primaries. Workup of this material to establish a correct diagnosis is time consuming and limited by the sparsity of material. In order to circumvent these drawbacks, the use of MALDI imaging MS (IMS) as a diagnostic platform has been explored. EXPERIMENTAL DESIGN: Cytology cell blocks from malignant effusions (serous ovarian carcinoma and several non-ovarian carcinomas including gastric adenocarcinoma) containing at least 30% neoplastic cells are selected for generation of cytology microarrays (CMA)...
October 11, 2018: Proteomics. Clinical Applications
Hui Lv, Lei Ye, Qian Liu, Song-Guo Li, Tao Li, Na-Li Huang, Yi Gao, Li-Bin Fan, Wei-Dong Du
PURPOSE: Epstein-Barr virus (EBV) is a ubiquitous human gamma herpes virus that infects human epithelial cells and B lymphocytes. It would be potentially valuable to develop novel combined assays to benefit screening for large panels of samples of EBV infectious diseases. EXPERIMENTAL DESIGN: A simple antigen-probed biochip that is modified with S-S-PEG-COOH and is used as a label-free high-throughput screening method for a combined detection of EBV capsid antigen IgM antibody, capsid antigen IgG antibody, and nuclear antigen IgG antibody...
October 11, 2018: Proteomics. Clinical Applications
Sophie Paczesny, Jochen Metzger
Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective form of tumor immunotherapy available to date. However, while HSCT can induce beneficial graft-versus-leukemia (GVL) effect, the adverse effect of graft-versus-host disease (GVHD), which is closely linked to GVL, is the major source of morbidity and mortality following HSCT. Until recently, available diagnostic and staging tools frequently fail to identify those at higher risk of disease progression or death. Furthermore, there are shortcomings in the prediction of the need for therapeutic interventions or the response rates to different forms of therapy...
October 11, 2018: Proteomics. Clinical Applications
Namita Pendharkar, Snigdha Dhali, Subodhini Abhang
PURPOSE: The study aims to discover and identify early grade diagnosis markers in tumor microenvironment and investigates their expression in serum. EXPERIMENTAL DESIGN: 2D fluorescence difference gel electrophoresis (2D-DIGE), a gel-based proteomics platform is used for tissue profiling and identifies deregulated proteins by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. Western blot validation for statistically significant six different proteins is performed in an independent cohort of participant serum...
October 3, 2018: Proteomics. Clinical Applications
Peggi M Angel, Kristina Schwamborn, Susana Comte-Walters, Cassandra Clift, Lauren E Ball, Anand S Mehta, Richard R Drake
PURPOSE: We recently reported a new method accessing proteins from extracellular matrix by imaging mass spectrometry (ECM IMS). ECM IMS was evaluated for use in exploring breast tissue pathologies. EXPERIMENTAL DESIGN: A tissue microarray (TMA) was analyzed that had 176 cores of biopsies and lumpectomies spanning breast pathologies of inflammation, hyperplasia, fibroadenoma, invasive ductal carcinoma and invasive lobular carcinoma and normal adjacent to tumor (NAT)...
September 24, 2018: Proteomics. Clinical Applications
Ali Azimi, Marina Ali, Kimberley L Kaufman, Graham J Mann, Pablo Fernandez-Penas
PURPOSE: Actinic keratoses (AK) are premalignant tumors that can be clinically difficult to differentiate from skin cancer. An easy, quick and reliable non-invasive alternative to biopsy is needed to definitively confirm the clinical diagnoses. This study evaluates Tape Stripping (TS) of stratum corneum (SC) for non-invasive biomarker analysis of AK. METHOD: Lesional and non-lesional human SC samples were obtained by application of stripping tapes on the skin of five AK patients...
September 24, 2018: Proteomics. Clinical Applications
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