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Proteomics. Clinical Applications

Marcus Jäger, Herbert P Jennissen, Marcel Haversath, André Busch, Thomas Grupp, Andrea Sowislok, Monika Herten
PURPOSE: Aseptic loosening in total joint replacement due to insufficient osteointegration is an unsolved problem in orthopaedics. The purpose of our study was to obtain a picture of the initial protein adsorption layer on femoral endoprosthetic surfaces as the key to the initiation of osseointegration. EXPERIMENTAL DESIGN: This paper describes the first study of femoral stem explants from patients for proteome analysis of the primary protein layer. After 2 min...
February 15, 2019: Proteomics. Clinical Applications
Alberto Ortiz
Kidney disease is one of the fastest growing causes of death worldwide, disclosing an unmet clinical need for early diagnosis and optimized risk stratification that allows high risk patient selection for clinical trials and for more intensive nephroprotective interventions in the clinic. The current issue of PROTEOMICS - Clinical Applications contains four manuscripts that explore different aspects of clinical proteomics implementation in the context of acute kidney injury, chronic kidney disease and, more specifically, diabetic kidney disease, and kidney transplantation from a diagnostic and risk stratification point of view...
February 15, 2019: Proteomics. Clinical Applications
Christian P Moritz, Yannick Tholance, Carole Rosier, Evelyne Federspiel, Juliette Svahn, Jean-Philippe Camdessanché, Jean-Christophe Antoine
PURPOSE: Identifying autoantigens of serological autoantibodies requires expensive methods, such as protein microarrays or immunoprecipitation plus mass spectrometry. Thus, sera are commonly pre-screened for interesting immunopatterns via immunocytochemistry/immunohistochemistry. However, distinguishing immunopatterns can be difficult and intracellular antigens are less accessible. Therefore, we present an alternative: a simple and cheap immunoblot screening able to detect proteins refractory to solubilization...
February 15, 2019: Proteomics. Clinical Applications
Alice C O'Farrell, Ian S Miller, Rhys Evans, Marina Alamanou, Maurice Cary, Girish Mallya Udupi, Adam Lafferty, Naser Monsefi, Mattia Cermona, Jochen Hm Prehn, Henk M Verheul, William M Gallagher, Mathias Gehrmann, Annette T Byrne
The tyrosine kinase inhibitor (TKI) sunitinib is a multi-targeted agent approved across multiple cancer indications. Nevertheless, since approval, data has emerged to describe a worrisome side effect profile including hypertension, hand-foot syndrome, fatigue, diarrhoea, mucositis, proteinuria and (rarely) congestive heart failure. It has been hypothesised that the observed multi-parameter toxicity profile is related to 'on-target' kinase inhibition in 'off-target' tissues. Herein, to interrogate off-target effects in pre-clinical studies, a reverse phase protein array (RPPA) approach was employed...
February 15, 2019: Proteomics. Clinical Applications
Maria Frantzi, Harald Mischak, Agnieszka Latosinska
No abstract text is available yet for this article.
February 14, 2019: Proteomics. Clinical Applications
Maria Frantzi, Agnieszka Latosinska, Harald Mischak
Mass spectrometry offers the potential of acquiring high resolution data depicting the functional status of a group of healthy or disease individuals, according to the different conditions. As most of the drugs are currently targeting proteins, proteomics has a dual value, both in the discovery of new molecules as therapeutic targets, but also as a methodology to perform high throughput drug profiling. As there is an evident need for drugs to be improved in terms of efficacy, a mechanistic insight for downstream effectors can be valuable in order to predict side effects and resistance mechanisms...
February 5, 2019: Proteomics. Clinical Applications
Elena Critselis
The recently implemented General Data Protection Regulation (GDPR) has promising attributes for ensuring the protection of personal data collected and processed for clinical proteomic investigations. However, there exist ever increasing alarming concerns regarding its implications upon the future of clinical proteomics research both within and beyond the European Union. The main issues of concern regard GDPR legislative requirements for informed consent for study subjects' data collection and processing, data anonymization, and data storage and/or sharing, particularly in research areas which readily utilize databanks and biobanks, such as clinical proteomics investigations...
February 1, 2019: Proteomics. Clinical Applications
Lona Zeneyedpour, Lennard J M Dekker, Jenny J M van Sten-van T Hoff, Peter C Burgers, Nick H T Ten Hacken, Theo M Luider
The goal of this manuscript is to explore the role of clinical proteomics for detecting mutations in COPD and lung cancer by mass spectrometry-based technology. COPD and lung cancer caused by smoke inhalation are most likely linked by challenging the immune system via partly shared pathways. GWAS have identified several single nucleotide polymorphisms (SNPs) which predispose an increased susceptibility to COPD and lung cancer. In lung cancer this leads to coding mutations in the affected tissues, development of neoantigens and different functionality and abundance of proteins in specific pathways...
January 31, 2019: Proteomics. Clinical Applications
Tianlin He
The application of protein (or peptide) biomarkers in clinical studies is a dynamic, ever-growing field. The introduction of clinical proteomics/ peptidomics, such as mass spectrometry- based assays and multiplexed antibody- based protein arrays, has reshaped the landscape of biomarker identification and validation, allowing the discovery of novel biomarkers at an unprecedented rate and reliability. To reflect the current status with respect to implementation of protein/peptide biomarkers, an investigation of the most recent (last 6 years) clinical studies from clinicaltrials...
January 31, 2019: Proteomics. Clinical Applications
Navid Sahebekhtiari, Mayank Saraswat, Sakari Joenväärä, Riikka Jokinen, Alen Lovric, Sanna Kaye, Adil Mardinoglu, Aila Rissanen, Jaakko Kaprio, Risto Renkonen, Kirsi H Pietiläinen
PURPOSE: The purpose of this study was to elucidate the effect of excess body weight and liver fat on the plasma proteome without interference from genetic variation. EXPERIMENTAL DESIGN: The effect of excess body weight was assessed in young, healthy monozygotic twins from pairs discordant for body mass index (intrapair difference (Δ) in BMI > 3 kg/m2, n = 26) with untargeted LC-MS proteomics quantification. The effect of liver fat was interrogated via subgroup analysis of the BMI-discordant twin cohort: liver fat discordant pairs (Δliver fat > 2%, n = 12) and liver fat concordant pairs (Δliver fat < 2%, n = 14), measured by magnetic resonance spectroscopy...
January 27, 2019: Proteomics. Clinical Applications
David Marx, Jochen Metzger, Jérôme Olagne, Iwona Belczacka, Stanislas Faguer, Magali Colombat, Holger Husi, William Mullen, Wilfried Gwinner, Sophie Caillard
PURPOSE: There is a need for accurate, robust, non-invasive methods to provide early diagnosis of graft lesions after kidney transplantation. A multitude of proteomic biomarkers for the major kidney allograft disease phenotypes defined by the BANFF classification criteria have been described in literature. None of these biomarkers have been established in the clinic. A key reason for this is the lack of clinical validation which is difficult, as even the gold standard of diagnosis, kidney biopsy, is often ambiguous...
January 25, 2019: Proteomics. Clinical Applications
Svein Olav Bratlie, Ville Wallenius, Anders Edebo, Lars Fändriks, Anna Casselbrant
BACKGROUND AND AIM: Dysplasia in Barrett's esophagus (BE) is regarded as a pre-neoplastic lesion. The renin-angiotensin system (RAS), which is known for its role in electrolyte homeostasis and hemodynamics, has also been shown to have tissue-based features linked to proliferation, inflammation, and cancer. RAS has been found to be associated with BE dysplasia. The aim of this study was to investigate possible effects of the RAS in BE dysplasia by using RAS-interfering pharmaceutical agents and by assessment of global protein expression in esophageal mucosal biopsies...
January 21, 2019: Proteomics. Clinical Applications
Vlasta Němcová-Fürstová, Kamila Balušíková, Petr Halada, Nela Pavlíková, Jan Šrámek, Jan Kovář
PURPOSE: Lipotoxicity is implicated in type 2 diabetes pathogenesis. Its molecular mechanisms are not completely understood. The aim of this study is to identify new suspect proteins involved in pancreatic β-cell death induction by saturated fatty acids and its inhibition by unsaturated fatty acids. EXPERIMENTAL DESIGN: Employing 2DE analysis and subsequent western blot confirmation, we assessed the differences in membrane/membrane-associated protein expression in human β-cell line NES2Y during cell death induction by stearate and its inhibition by oleate...
January 21, 2019: Proteomics. Clinical Applications
Fieke W Hoff, Chenyue W Hu, Amina A Qutub, Yihua Qiu, Marisa J Hornbaker, Carlos Bueso-Ramos, Hussein A Abbas, Sean M Post, Eveline S J M de Bont, Steven M Kornblau
PURPOSE: Acute promyelocytic leukemia (APL) is the most prognostically favorable subtype of AML. Defining the features that allow identification of acute promyelocytic leukemia (APL) patients likely to relapse after therapy remains challenging. EXPERIMENTAL DESIGN: Proteomic profiling was performed on 20 newly diagnosed APL, 205 non-APL acute myeloid leukemia (AML), and 10 normal CD34+ samples using Reverse Phase Protein Arrays probed with 230 antibodies. RESULTS: Comparison between APL and non-APL AML samples identified 8...
January 16, 2019: Proteomics. Clinical Applications
Agnieszka Gęgotek, Pedro Domingues, Adam Wroński, Ewa Ambrożewicz, Elżbieta Skrzydlewska
PURPOSE: Psoriatic skin lesions are associated with chronic inflammation related to immune cell activity. Therefore, the aim of this study was to compare changes in the proteome of psoriatic keratinocytes and lymphocytes. EXPERIMENTAL DESIGN: A proteomics approach (nanoflow LC-MS/MS) was used to analyze the expression of proteins in keratinocytes and lymphocytes from psoriatic patients and healthy controls. RESULTS: As a result 2119 proteins for keratinocytes and 1235 proteins for lymphocytes were identified, quantified, and assigned for further analysis...
January 16, 2019: Proteomics. Clinical Applications
Justyna Siwy, Thomas Klein, Marcel Rosler, Maximilan von Eynatten
PURPOSE: Chronic kidney disease (CKD) is a serious complication of hyperglycemia and treatment options to slow its progression are scarce. Dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used glucose-lowering drugs in type 2 diabetes (T2D). Among these, linagliptin has been suggested to exert kidney protective effects. We investigated whether a potential effect of linagliptin on kidney function could be unmasked by characterizing the urinary proteome profile (UPP) in T2D individuals with prevalent albuminuria...
January 11, 2019: Proteomics. Clinical Applications
Mohammad A Anwar, Darlene Liying Dai, Janet Wilson-McManus, Derek Smith, Gordon A Francis, Christoph H Borchers, Bruce M McManus, John S Hill, Gabriela V Cohen Freue
PURPOSE: A highly-multiplexed LC/ESI-MRM-MS based assay was developed for the identification of coronary artery disease (CAD) biomarkers in human plasma. EXPERIMENTAL DESIGN: The assay was used to measure 107 stable isotope labeled peptide standards and native peptides from 64 putative biomarkers of cardiovascular diseases in tryptic digests of plasma from subjects with (n = 70) and without (n = 45) angiographic evidence of CAD and no subsequent cardiovascular mortality during follow-up...
January 11, 2019: Proteomics. Clinical Applications
Frederik Persson, Peter Rossing
Precision medicine is since long an ongoing refinement of classical medicine, integrating improved and more detailed pathophysiological understanding with rapid technological advances. In the heterogenous are of chronic kidney disease there seems to be a high potential for improvement in treatment and prognosis for several causes, with new technologies under development, that have yet to be introduced in clinical practice. As in other medical disciplines, investigation of abundant peptide patterns (proteomics) has gained recent interest...
January 11, 2019: Proteomics. Clinical Applications
Zhen-Yu Zhang, Esther Nkuipou-Kenfack, Jan A Staessen
Diastolic heart failure (DHF) is characterized by slow left ventricular (LV) relaxation, increased LV stiffness, interstitial deposition of collagen, and a modified extracellular matrix proteins. Among Europeans, the frequency of asymptomatic diastolic LV dysfunction (DD) is 25%. This constitutes a large pool of people at high risk of DHF. The goal of this review was to describe the discovery and the initial validation of new multidimensional urinary peptidomic biomarkers (UPB) indicative of DD, mainly consisting of collagen fragments, and to describe a roadmap for their introduction in to clinical practice...
January 11, 2019: Proteomics. Clinical Applications
Elena Critselis, Marta Rava, Mirari Marquez, Vasiliki Lygirou, Despoina Chatzicharalambous, Panagiota Liapi, Ralph Lichtinghagen, Korbinian Brand, Lluís Cecchini, Antonia Vlahou, Nuria Malats, Jerome Zoidakis
PURPOSE: To evaluate the diagnostic and prognostic performance of Secreted Protein Acidic and Rich in Cysteine (SPARC) in detecting urinary bladder cancer (UBC). METHODS: Among the Integrated Study on Bladder Cancer (ISBLaC) study participants (n = 571; mean age:69.4±12.2 years), two cross-sectional studies assessed SPARC diagnostic performance in primary (n = 264, including 179 primary UBC patients and 85 urological controls) and recurrent (n = 307, including 56 recurrent UBC patients and 251 non-recurrent controls) UBC...
January 11, 2019: Proteomics. Clinical Applications
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