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Clinical Proteomics

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https://www.readbyqxmd.com/read/28820984/identification-of-m-tuberculosis-antigens-in-the-sera-of-tuberculosis-patients-using-biomimetic-affinity-chromatography-in-conjunction-with-esi-cid-ms-ms
#1
Guorong Ma, Jinting Pan, Jincheng Han, Lina Gao, Shulin Zhang, Rongxiu Li
The profiling of abnormally-expressed proteins in host cells using mass spectrometry (MS) analysis is a classical approach for screening disease-associated biomarkers in clinical diagnosis. However, few pathogen-specific antigens can currently be detected in serum using this proteomic approach, since these are very low-abundant proteins that are easily masked by host high-abundant proteins. Identification of pathogen-specific antigens in the sera of tuberculosis patients is crucial for the clinical diagnosis of this infectious disease, especially in immune-compromised patients...
July 31, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28820946/proteogenomic-investigation-of-strain-variation-in-clinical-mycobacterium-tuberculosis-isolates
#2
Tiaan Heunis, Anzaan Dippenaar, Robin M Warren, Paul D van Helden, Ruben G van der Merwe, Nicolaas C Gey van Pittius, Arnab Pain, Samantha L Sampson, David L Tabb
Mycobacterium tuberculosis consists of a large number of different strains that display unique virulence characteristics. Whole-genome sequencing has revealed substantial genetic diversity among clinical M. tuberculosis isolates, and elucidating the phenotypic variation encoded by this genetic diversity will be of utmost importance to fully understand M. tuberculosis biology and pathogenicity. In this study we integrated whole-genome sequencing and mass spectrometry (GeLC-MS/MS) to reveal strain-specific characteristics in the proteomes of two clinical M...
August 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28819369/in-vitro-cytotoxic-activities-of-the-oral-platinum-iv-prodrug-oxoplatin-and-hsp90-inhibitor-ganetespib-against-a-panel-of-gastric-cancer-cell-lines
#3
Lukas Klameth, Barbara Rath, Gerhard Hamilton
Gastric cancer exhibits a poor prognosis and is the third most common cause of cancer death worldwide. Chemotherapy of metastatic gastric cancer is based on combinations of platinum drugs and fluoropyrimidines, with added agents. Oxoplatin is a stable oral platinum(IV) prodrug which is converted to a highly active tetrachlorido(IV) complex under acidic conditions. In the present work, we studied the cytotoxic effects of oxoplatin against a panel of four gastric cancer cell lines in vitro. Furthermore, the role of HSP90 in chemoresistance of these lines was investigated using the specific inhibitor ganetespib...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819122/anti-inflammatory-drugs-suppress-ultrasound-mediated-mesenchymal-stromal-cell-tropism-to-kidneys
#4
Scott R Burks, Ben A Nguyen, Michele N Bresler, Matthew E Nagle, Saejeong J Kim, Joseph A Frank
Mesenchymal stromal cells (MSC) are potential renal therapeutics. Clinically, results are mixed partly because MSC tropism to kidneys is minimal following infusion. Ultrasound augmentation of the renal microenvironment is becoming increasingly-important in renal MSC therapies. We demonstrated pulsed-focused-ultrasound (pFUS) increases enhanced homing permeability and retention of MSC in mouse kidneys. Here, we characterized the temporal proteomic response to pFUS in mouse kidneys and its association with MSC tropism...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819023/therapeutic-effects-of-xpo1-inhibition-in-thymic-epithelial-tumors
#5
Fabio Conforti, Xu Zhang, Guanhua Rao, Tommaso De Pas, Yoko Yonemori, Jose A Rodriguez, Justine N McCutcheon, Raneen Rahhal, Anna T Alberobello, Yisong Wang, Yu-Wen Zhang, Udayan Guha, Giuseppe Giaccone
Exportin 1 (XPO1) mediates nuclear export of many cellular factors known to play critical roles in malignant processes, and selinexor (KPT-330) is the first XPO1-selective inhibitor of nuclear export (SINE) compound in advanced clinical development phase for cancer treatment. We demonstrated here that inhibition of XPO1 drives nuclear accumulation of important cargo tumor suppressor proteins (TSP) including transcription factor FOXO3a and p53 in thymic epithelial tumor (TET) cells and induces p53-dependent and -independent antitumor activity in vitro...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28815810/proteome-characterization-of-human-pancreatic-cyst-fluid-from-intraductal-papillary-mucinous-neoplasm-by-lc-ms-ms
#6
Joonho Park, Dohyun Han, Misol Do, Jongmin Woo, Joseph I Wang, Youngmin Han, Wooil Kwon, Sun-Whe Kim, Jin-Young Jang, Youngsoo Kim
RATIONALE: In recent years, the molecular components of pancreatic cyst fluid has been used for diagnosis and prognosis. Because the protein markers that are currently used in clinical tests are unreliable, proteomic studies to find new protein markers are being conducted. However, such researches have been limited due to the complexity of pancreatic cyst fluid and the immaturity of proteomic techniques. METHODS: To overcome these limitations and provide a pancreatic cyst proteome dataset, we examined cyst fluid proteome with tandem mass spectrometry...
August 15, 2017: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28815751/flow-cytometry-in-spermatology-a-bright-future-ahead
#7
REVIEW
C Ortega-Ferrusola, M C Gil, H Rodríguez-Martínez, L Anel, F J Peña, P Martín-Muñoz
Techniques such as mass spectrometry have led to unprecedented knowledge of the proteins that are present in the spermatozoa of humans and other mammals. However, in spite of their high-throughput and fractioning techniques, most of the techniques in use only offer average values for the entire sperm population. Yet, ejaculate is very heterogeneous, and average values may mask relevant biological information.The application of flow cytometry may overcome this disadvantage, allowing proteomic analysis at the single-cell level...
August 15, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28814976/analysis-of-proteomes-released-from-in-vitro-cultured-eight-clostridium-difficile-pcr-ribotypes-revealed-specific-expression-in-pcr-ribotypes-027-and-176-confirming-their-genetic-relatedness-and-clinical-importance-at-the-proteomic-level
#8
Jiri Dresler, Marcela Krutova, Alena Fucikova, Jana Klimentova, Veronika Hruzova, Miloslava Duracova, Katerina Houdkova, Barbora Salovska, Jana Matejkova, Martin Hubalek, Petr Pajer, Libor Pisa, Otakar Nyc
BACKGROUND: Clostridium difficile is the causative agent of C. difficile infection (CDI) that could be manifested by diarrhea, pseudomembranous colitis or life-threatening toxic megacolon. The spread of certain strains represents a significant economic burden for health-care. The epidemic successful strains are also associated with severe clinical features of CDI. Therefore, a proteomic study has been conducted that comprises proteomes released from in vitro cultured panel of eight different PCR ribotypes (RTs) and employs the combination of shotgun proteomics and label-free quantification (LFQ) approach...
2017: Gut Pathogens
https://www.readbyqxmd.com/read/28814946/protein-signatures-of-molecular-pathways-in-non-small-cell-lung-carcinoma-nsclc-comparison-of-glycoproteomics-and-global-proteomics
#9
Shuang Yang, Lijun Chen, Daniel W Chan, Qing Kay Li, Hui Zhang
BACKGROUND: Non-small cell lung carcinoma (NSCLC) remains the leading cause of cancer deaths in the United States. More than half of NSCLC patients have clinical presentations with locally advanced or metastatic disease at the time of diagnosis. The large-scale genomic analysis of NSCLC has demonstrated that molecular alterations are substantially different between adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). However, a comprehensive analysis of proteins and glycoproteins in different subtypes of NSCLC using advanced proteomic approaches has not yet been conducted...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/28814945/glomerular-abundance-of-complement-proteins-characterized-by-proteomic-analysis-of-laser-captured-microdissected-glomeruli-associates-with-progressive-disease-in-iga-nephropathy
#10
Teodora Ioana Flavia Paunas, Kenneth Finne, Sabine Leh, Hans-Peter Marti, Tom Eirik Mollnes, Frode Berven, Bjørn Egil Vikse
BACKGROUND: The clinical course of IgA nephropathy (IgAN) is variable and complement activation may predict prognosis. The present study investigated whether glomerular abundance of complement proteins associates with progression to end-stage renal disease (ESRD) in patients for whom prognosis could not be predicted based on clinical variables. METHODS: Based on data from the Norwegian Kidney Biopsy Registry and the Norwegian Renal Registry, three groups were included: IgAN patients with (n = 9) or without (n = 16) progression to ESRD during 10 years, and controls (n = 15) with a normal kidney biopsy...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/28814318/annexin-a2-could-enhance-multidrug-resistance-by-regulating-nf-%C3%AE%C2%BAb-signaling-pathway-in-pediatric-neuroblastoma
#11
Yi Wang, Kai Chen, Yihong Cai, Yuanxia Cai, Xiaojun Yuan, Lifeng Wang, Zhixiang Wu, Yeming Wu
BACKGROUND: Chemotherapy is one of major therapeutic regimens for neuroblastoma (NB) in children. However, recurrence and metastasis associated with poor prognosis caused by acquired multidrug resistance remains a challenge. There is a great need to achieve new insight into the molecular mechanism of drug resistance in NB. The aim of this study is to identify novel drug sensitivity-related biomarkers as well as new therapeutic targets to overcome chemoresistance. METHODS: We proteome-wide quantitatively compared protein expression of two NB cell lines with different drug sensitivities, isolated from the same patient prior to and following chemotherapy...
August 16, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28811553/cascaded-multi-view-canonical-correlation-camcco-for-early-diagnosis-of-alzheimer-s-disease-via-fusion-of-clinical-imaging-and-omic-features
#12
Asha Singanamalli, Haibo Wang, Anant Madabhushi
The introduction of mild cognitive impairment (MCI) as a diagnostic category adds to the challenges of diagnosing Alzheimer's Disease (AD). No single marker has been proven to accurately categorize patients into their respective diagnostic groups. Thus, previous studies have attempted to develop fused predictors of AD and MCI. These studies have two main limitations. Most do not simultaneously consider all diagnostic categories and provide suboptimal fused representations using the same set of modalities for prediction of all classes...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811376/in-vivo-loss-of-function-screens-identify-kpnb1-as-a-new-druggable-oncogene-in-epithelial-ovarian-cancer
#13
Michiko Kodama, Takahiro Kodama, Justin Y Newberg, Hiroyuki Katayama, Makoto Kobayashi, Samir M Hanash, Kosuke Yoshihara, Zhubo Wei, Jean C Tien, Roberto Rangel, Kae Hashimoto, Seiji Mabuchi, Kenjiro Sawada, Tadashi Kimura, Neal G Copeland, Nancy A Jenkins
Epithelial ovarian cancer (EOC) is a deadly cancer, and its prognosis has not been changed significantly during several decades. To seek new therapeutic targets for EOC, we performed an in vivo dropout screen in human tumor xenografts using a pooled shRNA library targeting thousands of druggable genes. Then, in follow-up studies, we performed a second screen using a genome-wide CRISPR/Cas9 library. These screens identified 10 high-confidence drug targets that included well-known oncogenes such as ERBB2 and RAF1, and novel oncogenes, notably KPNB1, which we investigated further...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28808996/preparation-and-immunoaffinity-depletion-of-fresh-frozen-tissue-homogenates-for-mass-spectrometry-based-proteomics-in-the-context-of-drug-target-biomarker-discovery
#14
DaRue A Prieto, King C Chan, Donald J Johann, Xiaoying Ye, Gordon Whitely, Josip Blonder
The discovery of novel drug targets and biomarkers via mass spectrometry (MS)-based proteomic analysis of clinical specimens has proven to be challenging. The wide dynamic range of protein concentration in clinical specimens and the high background/noise originating from highly abundant proteins in tissue homogenates and serum/plasma encompass two major analytical obstacles. Immunoaffinity depletion of highly abundant blood-derived proteins from serum/plasma is a well-established approach adopted by numerous researchers; however, the utilization of this technique for immunodepletion of tissue homogenates obtained from fresh frozen clinical specimens is lacking...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808043/allosteric-alterations-in-the-androgen-receptor-and-activity-in-prostate-cancer
#15
REVIEW
Takuma Uo, Stephen R Plymate, Cynthia C Sprenger
Organisms have evolved to generate biological complexity in their proteome and transcriptome from a limited number of genes. This concept holds true for the androgen receptor, which displays a diversity of inclusion/exclusion events in its structural motifs as a mechanism of resistance to the most forefront anti-androgen therapies. More than 20 androgen receptor variants that lack various portions of ligand-binding domain have been identified in human prostate cancer (PCa) samples. Most of the variants are inactive on their own, with a few exceptions displaying constitutive activity...
September 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28806058/metalloproteases-of-the-inner-mitochondrial-membrane
#16
Roman Levytskyy, Iryna Bohovych, Oleh Khalimonchuk
The inner mitochondrial membrane (IM) is among most protein-rich cellular compartments. The metastable IM sub-proteome where the concentration of proteins is approaching oversaturation creates a challenging protein folding environment with high probability for protein malfunction or aggregation. Failure to maintain protein homeostasis in such a setting can impair functional integrity of the mitochondria and drive clinical manifestations. The IM is equipped with a series of highly conserved, proteolytic complexes dedicated to the maintenance of normal protein homeostasis within this mitochondrial sub-compartment...
August 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/28802583/cytoskeleton-and-nuclear-lamina-affection-in-recessive-osteogenesis-imperfecta-a-functional-proteomics-perspective
#17
Assunta Gagliardi, Roberta Besio, Chiara Carnemolla, Claudia Landi, Alessandro Armini, Mona Aglan, Ghada Otaify, Samia A Temtamy, Antonella Forlino, Luca Bini, Laura Bianchi
Osteogenesis imperfecta (OI) is a collagen-related disorder associated to dominant, recessive or X-linked transmission, mainly caused by mutations in type I collagen genes or in genes involved in type I collagen metabolism. Among the recessive forms, OI types VII, VIII, and IX are due to mutations in CRTAP, P3H1, and PPIB genes, respectively. They code for the three components of the endoplasmic reticulum complex that catalyzes 3-hydroxylation of type I collagen α1Pro986. Under-hydroxylation of this residue leads to collagen structural abnormalities and results in moderate to lethal OI phenotype, despite the exact molecular mechanisms are still not completely clear...
August 9, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28802308/vitreous-amyloidosis-with-autonomic-neuropathy-of-the-digestive-tract-associated-with-a-novel-transthyretin-p-gly87arg-variant-in-a-bangladeshi-patient-a-case-report
#18
Benjamin Terrier, Magali Colombat, Caroline Beugnet, Astrid Quéant, Jonathan London, Jean-Baptiste Daudin, Claire Le Jeunne, Luc Mouthon, Dominique Monnet, Cécile Cauquil, Catherine Lacroix, David Adams, Antoine Brézin, Sophie Valleix
BACKGROUND: Hereditary transthyretin amyloidosis is an autosomal dominant inherited disorder, first described in families with sensorimotor and autonomic neuropathy. Since its first description, more than 120 amyloidogenic transthyretin mutations have been reported with various geographic distributions and associated with a wide range of phenotypes involving the peripheral nerve, the heart, the gastrointestinal tract, the eyes, the central nervous system, or the kidneys. In some cases of transthyretin amyloidosis, the first clinical manifestation is vitreous opacity...
August 13, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28800743/an-itraq-based-proteomic-analysis-reveals-dysregulation-of-neocortical-synaptopodin-in-lewy-body-dementias
#19
Arnab Datta, Yuek Ling Chai, Jing Min Tan, Jasinda H Lee, Paul T Francis, Christopher P Chen, Siu Kwan Sze, Mitchell K P Lai
Lewy body dementias are the second most common cause of neurodegenerative dementia in the elderly after Alzheimer's disease (AD). The two clinical subgroups of Lewy body dementias, namely, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), are differentiated by the chronology of cognitive symptoms relative to parkinsonism. At present, there remains a debate on whether DLB and PDD are separate disease entities, or fall within the same spectrum of Lewy body dementias. In this study, we compared the detergent-soluble proteome via an 8-plex isobaric tag for relative and absolute quantitation (iTRAQ) analysis of pooled lysates from the prefrontal cortex (BA9) of DLB (n = 19) and PDD (n = 21) patients matched a priori for amyloid (total Aβ42) burden, semi-quantitative scores for Lewy bodies and neurofibrillary tangles together with age-matched control (n = 21) subjects...
August 11, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28799854/proteomic-studies-in-the-discovery-of-cerebrospinal-fluid-biomarkers-for-amyotrophic-lateral-sclerosis
#20
Peggy Barschke, Patrick Oeckl, Petra Steinacker, Albert Ludolph, Markus Otto
Amyotrophic lateral sclerosis (ALS) is a progressive degenerative motor neuron disease, which usually leads to death within a few years. The diagnosis is mainly based on clinical symptoms and there is a need for ALS-specific biomarkers to make an early and precise diagnosis, for development of disease-modifying drugs and to gain new insights into pathophysiology. Areas covered: In the present review, we summarize studies using mass spectrometric (MS) approaches to identify protein alterations in the cerebrospinal fluid (CSF) of ALS patients...
August 14, 2017: Expert Review of Proteomics
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