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Clinical Proteomics

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https://www.readbyqxmd.com/read/28227691/understanding-the-cochlear-implant-environment-by-mapping-perilymph-proteomes-from-different-species
#1
Jonathan C Palmer, Megan S Lord, Jeremy L Pinyon, Andrew K Wise, Nigel H Lovell, Paul M Carter, Ya Lang Enke, Gary D Housley, Rylie A Green, Jonathan C Palmer, Megan S Lord, Jeremy L Pinyon, Andrew K Wise, Nigel H Lovell, Paul M Carter, Ya Lang Enke, Gary D Housley, Rylie A Green, Ya Lang Enke, Rylie A Green, Jonathan C Palmer, Nigel H Lovell, Paul M Carter, Jeremy L Pinyon, Gary D Housley, Andrew K Wise, Megan S Lord
Cochlear implants operate within a bony channel of the cochlea, bathed in a fluid known as the perilymph. The perilymph is a complex fluid containing ions and proteins, which are known to actively interact with metallic electrodes. To improve our understanding of how cochlear implant performance varies in preclinical in vivo studies in comparison to human trials and patient outcomes, the protein composition (or perilymph proteome) is needed. Samples of perilymph were gathered from feline and guinea pig subjects and analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) to produce proteomes and compare against the recently published human proteome...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28223349/identification-of-antibody-targets-for-tuberculosis-serology-using-high-density-nucleic-acid-programmable-protein-arrays
#2
Lusheng Song, Garrick Wallstrom, Xiaobo Yu, Marika Hopper, Jennifer Van Duine, Jason Steel, Jin Park, Peter Wiktor, Peter Khan, Al Brunner, Douglas Wilson, Elizabeth R Jenny-Avital, Ji Qiu, Joshua LaBaer, D Mitchell Magee, Jacqueline M Achkar
Better and more diverse biomarkers for the development of simple point-of-care tests for active tuberculosis (TB), a clinically heterogeneous disease, are urgently needed. We generated a proteomic Mycobacterium tuberculosis (Mtb) High-Density Nucleic Acid Programmable Protein Array (HD-NAPPA) that used a novel multiplexed strategy for expedited high-throughput screening for antibody responses to the Mtb proteome. We screened sera from HIV uninfected and co-infected TB patients and controls (n = 120) from the US and South Africa (SA) using the multiplex HD-NAPPA for discovery, followed by deconvolution and validation through single protein HD-NAPPA with biologically independent samples (n=124)...
February 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28223226/targeted-protein-degradation-by-protacs
#3
REVIEW
Taavi K Neklesa, James D Winkler, Craig M Crews
Targeted protein degradation using the PROTAC technology is emerging as a novel therapeutic method to address diseases driven by the aberrant expression of a disease-causing protein. PROTAC molecules are bifunctional small molecules that simultaneously bind a target protein and an E3-ubiquitin ligase, thus causing ubiquitination and degradation of the target protein by the proteasome. Like small molecules, PROTAC molecules possess good tissue distribution and the ability to target intracellular proteins. Herein, we highlight the advantages of protein degradation using PROTACs, and provide specific examples where degradation offers therapeutic benefit over classical enzyme inhibition...
February 13, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28223106/diagnosis-of-major-depressive-disorder-by-combining-multimodal-information-from-heart-rate-dynamics-and-serum-proteomics-using-machine-learning-algorithm
#4
Eun Young Kim, Min Young Lee, Se Hyun Kim, Kyooseob Ha, Kwang Pyo Kim, Yong Min Ahn
OBJECTIVE: Major depressive disorder (MDD) is a systemic and multifactorial disorder that involves abnormalities in multiple biochemical pathways and the autonomic nervous system. This study applied a machine-learning method to classify MDD and control groups by incorporating data from serum proteomic analysis and heart rate variability (HRV) analysis for the identification of novel peripheral biomarkers. METHODS: The study subjects consisted of 25 drug-free female MDD patients and 25 age- and sex-matched healthy controls...
February 18, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28221173/new-developments-in-transplant-proteomics
#5
Julie Ho, Patricia Hirt-Minkowski, John A Wilkins
PURPOSE OF REVIEW: Despite modern immunosuppression, renal allograft rejection remains a major contributor to graft loss. Novel biomarkers may help improve posttransplant outcomes through the early detection and treatment of rejection. Our objective is to provide an overview of proteomics, review recent discovery-based rejection studies, and explore innovative approaches in biomarker development. RECENT FINDINGS: Urine MMP7 was identified as a biomarker of subclinical and clinical rejection using two-dimensional liquid chromatography tandem-mass spectrometry (LC-MS/MS) and improved the overall diagnostic discrimination of urine CXCL10 : Cr alone for renal allograft inflammation...
February 17, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28220199/-novel-pharmaceutical-treatment-approaches-for-gastric-cancer
#6
F Lordick
This review article delineates novel approaches for the pharmaceutical treatment of gastric cancer. A newly developed molecular classification of gastric cancer based on histology, genetic, epigenetic and proteomic characteristics has evolved. It provides a road map for development of new drugs and combinations as well as for patient stratification in clinical research and it is expected to be introduced into clinical practice in the near future. Anti-HER2 targeted treatment is a validated strategy for treatment of metastatic gastric cancer and is now also being studied in the perioperative setting to increase response rates and ultimately survival in patients undergoing curative surgery; however, the resistance mechanisms of HER2-targeted treatment are poorly understood and optimal patient selection remains challenging...
February 20, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28219823/proteomic-analysis-of-a-carbapenem-resistant-klebsiella-pneumoniae-strain-in-response-to-meropenem-stress
#7
Arbab Khan, Divakar Sharma, Mohammad Faheem, Deepa Bisht, Asad U Khan
OBJECTIVES: Antibiotic resistance has become a major problem in treating bacterial infections. The aim of this study was to elucidate the effects of meropenem on a blaKPC-2-harbouring multidrug-resistant clinical strain of Klebsiella pneumoniae through a proteomics approach in order to attain a deeper understanding of bacterial resistance strategies. METHODS: Analysis was performed by two-dimensional gel electrophoresis of whole-cell extracts of bacteria exposed to a sublethal concentration of meropenem compared with the untreated control...
February 17, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/28219319/biomarkers-in-alzheimer-s-disease-recent-update
#8
Sushil Sharma, Walter Lipincott
Alzheimer disease (AD) is an age-related neurodegenerative disorder, characterized by loss of memory and cognitive function. It is the common cause of dementia in elderly and is a global health concern as the population of people aged 85 and older, is growing alarmingly. Although pharmacotherapy for the treatment of AD has improved, lot of work remains to treat this devastating disease. AD pathology begins even before the onset of clinical symptoms. Because therapies could be more effective if implemented early in the disease progression, it is highly prudent to discover reliable biomarkers, to detect its exact pathophysiology during pre-symptomatic stage...
February 20, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28218733/integrating-pharmacoproteomics-into-early-phase-clinical-development-state-of-the-art-challenges-and-recommendations
#9
REVIEW
Savita Nandal, Tal Burt
Pharmacoproteomics is the study of disease-modifying and toxicity parameters associated with therapeutic drug administration, using analysis of quantitative and temporal changes to specific, predetermined, and select proteins, or to the proteome as a whole. Pharmacoproteomics is a rapidly evolving field, with progress in analytic technologies enabling processing of complex interactions of large number of unique proteins and effective use in clinical trials. Nevertheless, our analysis of clinicaltrials.gov and PubMed shows that the application of proteomics in early-phase clinical development is minimal and limited to few therapeutic areas, with oncology predominating...
February 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28216434/human-nlrp3-inflammasome-activity-is-regulated-by-and-potentially-targetable-via-btk
#10
Xiao Liu, Tica Pichulik, Olaf-Oliver Wolz, Truong-Minh Dang, Andrea Stutz, Carly Dillen, Magno Delmiro Garcia, Helene Kraus, Sabine Dickhöfer, Ellen Daiber, Lisa Münzenmayer, Silke Wahl, Nikolaus Rieber, Jasmin Kümmerle-Deschner, Amir Yazdi, Mirita Franz-Wachtel, Boris Macek, Markus Radsak, Sebastian Vogel, Berit Schulte, Juliane Sarah Walz, Dominik Hartl, Eicke Latz, Stephan Stilgenbauer, Bodo Grimbacher, Lloyd Miller, Cornelia Brunner, Christiane Wolz, Alexander N R Weber
BACKGROUND: The Nod-like receptor, NACHT, LRR and PYD domains-containing protein 3 (NLRP3), and Bruton's tyrosine kinase (BTK) are protagonists in innate and adaptive immunity, respectively: NLRP3 senses exogenous and endogenous insults leading to inflammasome activation, which occurs spontaneously in Muckle-Wells Syndrome (MWS); BTK mutations cause the genetic immunodeficiency X-linked agammaglobulinemia (XLA). However, to date few proteins that regulate NLRP3 inflammasome activity in human primary immune cells have been identified and clinically promising pharmacological targeting strategies remain elusive...
February 16, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28214264/identification-of-candidate-cerebrospinal-fluid-biomarkers-in-parkinsonism-using-quantitative-proteomics
#11
N K Magdalinou, A J Noyce, R Pinto, E Lindstrom, J Holmén-Larsson, M Holtta, K Blennow, H R Morris, T Skillbäck, T T Warner, A J Lees, I Pike, M Ward, H Zetterberg, J Gobom
INTRODUCTION: Neurodegenerative parkinsonian syndromes have significant clinical and pathological overlap, making early diagnosis difficult. Cerebrospinal fluid (CSF) biomarkers may aid the differentiation of these disorders, but other than α-synuclein and neurofilament light chain protein, which have limited diagnostic power, specific protein biomarkers remain elusive. OBJECTIVES: To study disease mechanisms and identify possible CSF diagnostic biomarkers through discovery proteomics, which discriminate parkinsonian syndromes from healthy controls...
January 31, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28212922/organ-specific-biomarkers-in-lupus
#12
REVIEW
Haijing Wu, Jinrong Zeng, Ming Zhao, Qianjin Lu
Systemic lupus erythematosus (SLE) is a complex and highly heterogeneous disease, which affects multiple organs, including joints, skin, kidneys, heart, hematopoietic system, and nerve system. While the etiopathogenesis of SLE still remains unclear, genetic susceptibilities and aberrant epigenetic modifications are believed to be involved. For precision therapy, it is necessary to assess accurately and objectively organ involvements and disease activity, which is difficult by current clinical laboratory tests...
February 14, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28212573/dynamic-variations-in-epithelial-to-mesenchymal-transition-emt-atm-and-slfn11-govern-response-to-parp-inhibitors-and-cisplatin-in-small-cell-lung-cancer
#13
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignatio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28205040/clinical-phenotyping-of-heart-failure-with-biomarkers-current-and-future-perspectives
#14
REVIEW
Vichai Senthong, Jennifer L Kirsop, W H Wilson Tang
INTRODUCTION: Heart failure (HF) is a complex clinical syndrome with diverse risk factors and etiologies, differing underlying pathophysiology, and large phenotypic heterogeneity. RECENT FINDINGS: Advances in imaging techniques coupled with clinical trials that targeted only in those with impaired left ventricular ejection fraction (LVEF) have largely shaped the current management strategy for HF that focuses predominantly in patients with systolic HF. In contrast, there are no effective treatments for HF with preserved ejection fraction (HFpEF)...
February 15, 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/28201995/zoonotic-necrotizing-myositis-caused-by-streptococcus-equi-subsp-zooepidemicus-in-a-farmer
#15
Bård Reiakvam Kittang, Veronika Kuchařová Pettersen, Oddvar Oppegaard, Dag Harald Skutlaberg, Håvard Dale, Harald G Wiker, Steinar Skrede
BACKGROUND: Streptococcus equi subsp. zooepidemicus is a beta-hemolytic group C streptococcus mainly causing infections in domesticated animals. Here we describe the first case of zoonotic necrotizing myositis caused by this bacterium. CASE PRESENTATION: The patient was a 73-year-old, previously healthy farmer with two asymptomatic Shetland ponies in his stable. After close contact with the ponies while feeding them, he rapidly developed erythema of his left thigh and sepsis with multiple organ failure...
February 15, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28199984/autocrine-and-paracrine-stip1-signaling-promote-osteolytic-bone-metastasis-in-renal-cell-carcinoma
#16
Jiang Wang, Hongbo You, Jun Qi, Caihong Yang, Ye Ren, Hao Cheng
Bone metastases are responsible for some of the most devastating complications of renal cell carcinoma (RCC). However, pro-metastatic factors leading to the highly osteolytic characteristics of RCC bone metastasis have barely been explored. We previously developed novel bone-seeking RCC cell lines by the in vivo selection strategy and performed a comparative proteome analysis on their total cell lysate. Here, we focused on STIP1 (stress-induced phosphoprotein 1), the high up-regulated protein in the bone-seeking cells, and explored its clinical relevance and functions in RCC bone metastasis...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28196893/phosphorylation-of-%C3%AE-b-crystallin-supports-reactive-astrogliosis-in-demyelination
#17
Hedwich F Kuipers, Jane Yoon, Jack van Horssen, May H Han, Paul L Bollyky, Theo D Palmer, Lawrence Steinman
The small heat shock protein αB-crystallin (CRYAB) has been implicated in multiple sclerosis (MS) pathogenesis. Earlier studies have indicated that CRYAB inhibits inflammation and attenuates clinical disease when administered in the experimental autoimmune encephalomyelitis model of MS. In this study, we evaluated the role of CRYAB in primary demyelinating events. Using the cuprizone model of demyelination, a noninflammatory model that allows the analysis of glial responses in MS, we show that endogenous CRYAB expression is associated with increased severity of demyelination...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28195677/plasma-prefractionation-methods-for-proteomic-analysis-and-perspectives-in-clinical-applications
#18
Somchai Chutipongtanate, Supawat Chatchen, Jisnuson Svasti
Plasma is a rich source of biomarkers with clinical relevance. However, the wide dynamic range of protein concentration hinders the detection of low abundance proteins. Plasma prefractionation methods serve as indispensable tools to reduce plasma complexity, allowing the opportunity to explore tissue-derived proteins which leak into the circulation. This review summarizes common approaches in plasma prefractionation methods for proteomic analysis and then discusses some considerations in plasma prefractionation for clinical applications, reviewing some examples of its use in clinical situations...
February 14, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28193222/phosphorylation-dependent-regulation-of-aldh1a1-by-aurora-kinase-a-insights-on-their-synergistic-relationship-in-pancreatic-cancer
#19
Jing Wang, Kumar Nikhil, Keith Viccaro, Lei Chang, Jacoba White, Kavita Shah
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) formation are key underlying causes that promote extensive metastasis, drug resistance, and tumor recurrence in highly lethal pancreatic cancer. The mechanisms leading to EMT and CSC phenotypes are not fully understood, which has hindered the development of effective targeted therapies capable of improving treatment outcomes in patients with pancreatic cancer. RESULTS: We show a central role of Aurora kinase A (AURKA) in promoting EMT and CSC phenotypes via ALDH1A1, which was discovered as its direct substrate using an innovative chemical genetic screen...
February 13, 2017: BMC Biology
https://www.readbyqxmd.com/read/28193034/leveraging-gas-phase-fragmentation-pathways-for-improved-identification-and-selective-detection-of-targets-modified-by-covalent-probes
#20
Scott B Ficarro, Christopher M Browne, Joseph D Card, William M Alexander, Tinghu Zhang, Eunyoung Park, Randall McNally, Sirano Dhe-Paganon, Hyuk-Soo Seo, Ilaria Lamberto, Michael J Eck, Sara J Buhrlage, Nathanael S Gray, Jarrod A Marto
The recent approval of covalent inhibitors for multiple clinical indications has reignited enthusiasm for this class of drugs. As interest in covalent drugs has increased, so too has the need for analytical platforms that can leverage their mechanism-of-action to characterize modified protein targets. Here we describe novel gas phase dissociation pathways which yield predictable fragment ions during MS/MS of inhibitor-modified peptides. We find that these dissociation pathways are common to numerous cysteine-directed probes as well as the covalent drugs, Ibrutinib and Neratinib...
December 20, 2016: Analytical Chemistry
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