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Proteomics. Clinical Applications

Natalia Tiberti, Jean-Charles Sanchez
Sleeping sickness is a neglected tropical disease caused by Trypanosoma brucei parasites, affecting the poorest communities in sub-Saharan Africa. The great efforts done by the scientific community, local governments and non-governmental organizations (NGOs) via active patients' screening, vector control and introduction of improved treatment regimens have significantly contributed to the reduction of HAT incidence during the last 15 years. Consequently, the WHO has announced the objective of HAT elimination as a public health problem by 2020...
March 8, 2018: Proteomics. Clinical Applications
Lian Gui, Qianqian Zhang, Yan Cai, Xiaohong Deng, Yingke Zhang, Cheukfai Li, Qi Guo, Xiaoshun He, Junqi Huang
Previous studies have demonstrated that let-7e is associated with inflammatory responses. To date, the roles and mechanisms of let-7e have not been completely revealed. To identify proteins associated with let-7e overexpression and explore their functions in the immune responses, including in cytokine production, we used high-throughput isobaric tag for relative and absolute quantitation (iTRAQ) technology to provide the first genome-wide study of THP-1 cells transfected with let-7e mimic followed by lipopolysaccharide (LPS) stimulation...
March 5, 2018: Proteomics. Clinical Applications
Bhagyashree Nandakishor Swarge, Winfried Roseboom, Linli Zheng, Wishwas R Abhyankar, Stanley Brul, Chris G Koster, Leo J Koning
PURPOSE: Bacterial endospores, the transmissible forms of pathogenic bacilli and clostridia, are heterogeneous multilayered structures composed of proteins. These proteins protect the spores against variety of stresses, thus helping spore survival, and assist in germination, by interacting with the environment to form vegetative cells. Owing to the complexity, insolubility, and dynamic nature of spore proteins, it has been difficult to obtain their comprehensive protein profiles. EXPERIMENTAL DESIGN: The intact spores of Bacillus subtilis, Bacillus cereus, and Peptoclostridium difficile and their vegetative counterparts were disrupted by bead-beating in 6M urea under reductive conditions...
February 27, 2018: Proteomics. Clinical Applications
Min-Sun Jin, Hyebin Lee, Jongmin Woo, Seongmin Choi, Mi Sol Do, Kwangsoo Kim, Min Ji Song, Youngsoo Kim, In Ae Park, Dohyun Han, Han Suk Ryu
PURPOSE: Secretory carcinoma (SC) of the breast is defined as an indolent tumor but is still categorized into a basal-like triple-negative breast cancer (BL-TNBC) subgroup that generally shows aggressive behaviour according to the current classification. Despite the unique clinical behaviour of SC, molecular characteristics that reflect biological behaviours of SC remain largely unknown. EXPERIMENTAL DESIGN: We employed a combinatorial approach of whole-exome sequencing and mass spectrometry-based in-depth quantitative proteomics to determine the entire molecular landscape of SC using three SC formalin-fixed paraffin-embedded (FFPE) tissues...
February 24, 2018: Proteomics. Clinical Applications
Andrea Padoan
The successful use of proteomic technology for the discovery of clinically-relevant, new candidate biomarkers, especially in the low molecular weight range (peptidome), calls for a careful consideration of standardized operating procedures (SOP) for pre-analytical variables, including samples handling and storage. The current lack of standardization, widely considered a relevant source of random and systematic errors, underlies the uncertainty of analytical results and poor comparability, especially in multi-centric or inter-laboratory studies...
February 24, 2018: Proteomics. Clinical Applications
Juhura G Almazi, Peter Pockney, Craig Gedye, Nathan D Smith, Hubert Hondermarck, Nicole M Verrills, Matthew D Dun
BACKGROUND: Optimized blood collection tubes (BCT) have been developed to expand the utility of plasma cell free DNA (cfDNA) and are in clinical use. The appropriateness of plasma collected and stored in these tubes for proteomic analysis is unknown. METHODS: Paired blood samples were collected in BCT and traditional K3EDTA (EDTA) tubes from healthy controls, and from colorectal cancer patients (CRC) before and after surgery, and stored for between 45 minutes and 48 hours at room temperature...
February 24, 2018: Proteomics. Clinical Applications
Neeloo Singh, Renu Goel, Ekta Jain
PURPOSE: Although in trypanosomatids, monoxeny (Leptomonas) is ancestral to dixeny (Leishmania), however clinical cases of visceral leishmanisis with Leptomonas co-infection are increasingly being reported from India. Using a proteogenomic approach, we carried out a detailed proteome analysis of these two kinetoplastid parasites viz. Leishmania and its sister Leptomonas, to catalog the key proteins associated with and therefore possibly responsible for phenotype changes in Leptomonas evolution and domestication as co-infection with Leishmania...
February 22, 2018: Proteomics. Clinical Applications
Ying Liu, Yi-Ran Tan, Wen-Wen Sun, Wu-Tong Ju, Yong Fu, Li-Zhen Wang, Jiang Li, Chen-Ping Zhang, Zhi-Yuan Zhang, Lai-Ping Zhong
PURPOSE: To find the potential biomarkers in in the diagnostic model of oral and squamous cell carcinoma (OSCC), and to further validate the biomarker. EXPERIMENTAL DESIGN: With the MALDI-TOF-MS analysis between tissues from oral cancer patients and normal oral mucosa from healthy controls, scara5 was found to be potentially significant after searching the protein database. In addition, Immunohistochemical staining, PCR, ELISA and western blot technique were used to detect scara5 expression in clinical samples and cell lines...
February 20, 2018: Proteomics. Clinical Applications
Jarrod J Sandow, Adam Rainczuk, Giuseppe Infusini, Ming Makanji, Maree Bilandzic, Amy L Wilson, Nicole Fairweather, Peter G Stanton, Daniel Garama, Daniel Gough, Thomas W Jobling, Andrew I Webb, Andrew N Stephens
PURPOSE: For the vast majority of ovarian cancer patients, optimal surgical debulking remains a key prognostic factor associated with improved survival. A standardized, biomarker-based test, to pre-operatively discriminate benign from malignant disease and inform appropriate patient triage, is highly desirable. However, no fit-for-purpose biomarkers have yet been identified. EXPERIMENTAL DESIGN: We conducted a pilot study consisting of 40 patient urine samples (20 from each group), using label-free quantitative (LFQ) mass spectrometry, to identify potential biomarker candidates in urine from individual ovarian cancer patients...
February 9, 2018: Proteomics. Clinical Applications
Shuang Yang, Subroto Chatterjee, John Cipollo
With recent advancements of analytical techniques and mass spectrometric instrumentations, proteomics has been widely exploited to study the regulation of protein expression associated with disease states. Many proteins may undergo abnormal change in response to the stimulants, leading to regulation of post-translationally modified proteins. In this review, we discuss the physiological and pathological roles of protein glycosylation in cardiac hypertrophy, and how the signal pathways regulate heart function and leading to heart failure...
February 9, 2018: Proteomics. Clinical Applications
Angela Baralla, Alessandro G Fois, Elisabetta Sotgiu, Elisabetta Zinellu, Arduino A Mangoni, Salvatore Sotgia, Angelo Zinellu, Pietro Pirina, Ciriaco Carru
PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and abnormal inflammatory response of the lungs to inhaled noxious particles or gases. We used a proteomic approach with 2-DE followed by MALDI TOF-MS analyses in order to identify potential biomarkers in the early stages of the disease: GOLD stage mild and moderate. EXPERIMENTAL DESIGN: Blood plasma was collected from 43 patients with mild and moderate COPD as well as from 43 age and sex matched control subjects...
February 7, 2018: Proteomics. Clinical Applications
Manish Kumar, Chakrakodi N Varun, Gourav Dey, Raju Ravikumar, Anita Mahadevan, Susarla Krishna Shankar, T S Keshava Prasad
PURPOSE: The objective of this study was to study the altered proteome in the frontal lobe of patients with CM. Unbiased analysis of differentially abundant proteins could lead to identification of host responses against P. falciparum infection, which will aid in better understanding of the molecular mechanism of pathophysiology in CM. EXPERIMENTAL DESIGN: We employed TMT-based quantitative proteomic analysis using high-resolution mass spectrometry. In brief, proteins were isolated from frontal lobe samples, which were collected at autopsy from three cases of CM and three control subjects...
February 1, 2018: Proteomics. Clinical Applications
Ling Chen, Weibo Zhao, Jing He, Liqi Li, Dong Meng, Dongyan Cai, Jinjin Yu, Daozhen Chen, Yibo Wu, Tao Zhou
PURPOSE: Lymph node status is a crucial predictor for the overall survival of invasive breast cancer. However, lymph node involvement is only detected in about half of HER2-positive patients. Since patients with lymph node involvement has less favorable prognosis and higher risk of recurrence, it is important to develop plasma protein biomarkers for distinguishing lymph node metastasis. EXPERIMENTAL DESIGN: A label-free quantitative proteomic strategy to construct plasma proteomes of ten patients with small size HER2-positive breast cancer (five patients with lymph node metastasis versus five patients without lymph node metastasis) is applied...
January 31, 2018: Proteomics. Clinical Applications
Junjie Mao, Xiaojun Hu, Pengfei Pang, Bin Zhou, Yaqin Zhang, Dan Li, Hong Shan
PURPOSE: To clarify the role of Cysteinyl leukotrienes receptor type 1 (CYSLTR1) and find the potential predictors of CYSLTR1 antagonists (LTRAs) responsiveness in vivo. EXPERIMENTAL DESIGN: Cysltr1 knockout (KO) mouse model was established by the CRISPR/Cas9 system. The phenotype of Cysltr1 KO mice were tested by western blotting (WB), histological examinations, and experiment of zymosan A-induced peritoneal inflammation. The differentially expressed proteins (DEPs) between the Cysltr1 KO and the wild type (WT) mice lung tissues were analyzed by the iTRAQ-based proteomic technology...
January 26, 2018: Proteomics. Clinical Applications
Anna Perzanowska, Agnieszka Fatalska, Grzegorz Wojtas, Andrzej Lewandowicz, Agata Michalak, Grzegorz Krasowski, Christoph H Borchers, Michal Dadlez, Dominik Domanski
PURPOSE: The goal of this work was to develop an LC-MRM assay for the quantitative analysis of a set of established and diagnostically important cytokeratin (CK) markers used in cancer diagnosis, prognosis and therapy monitoring. Secondly, the potential of this assay in lung cancer diagnosis through pleural effusion (PE) analysis was examined. EXPERIMENTAL DESIGN: A multiplexed MRM assay was developed for 17 CKs and their select caspase-cleaved fragments. Isotope-labeled standard peptides were used for high assay specificity and absolute peptide quantitation; with robust standard-flow LC coupled to a latest-generation triple-quadrupole instrument for high sensitivity...
January 19, 2018: Proteomics. Clinical Applications
Li-Bo Yan, You-Jia Yu, Qing-Bo Zhang, Xiao-Qiong Tang, Lang Bai, FeiJun Huang, Hong Tang
PURPOSE: The aim of this study was to screen for novel host proteins that play a role in HBx augmenting HBV replication. EXPERIMENTAL DESIGN: Three HepG2 cell lines stably harboring different functional domain of HBx (HBx, HBx-Cm6, and HBx-Cm16) were cultured. ITRAQ technology integrated with LC-MS/MS analysis was applied to identify the proteome differences among these three cell lines. RESULTS: In brief, a total of 70 different proteins were identified among HepG2-HBx, HepG2-HBx-Cm6, and HepG2-HBx-Cm16 by double repetition...
January 19, 2018: Proteomics. Clinical Applications
Yung-Chin Hsiao, Lichieh Julie Chu, Yi-Ting Chen, Lang-Ming Chi, Kun-Yi Chien, Wei-Fan Chiang, Ya-Ting Chang, Szu-Fan Chen, Wei-Shun Wang, Yao-Ning Chuang, Shih-Yu Lin, Chih-Yen Chien, Kai-Ping Chang, Yu-Sun Chang, Jau-Song Yu
PURPOSE: Saliva is an attractive sample source for the biomarker-based testing of several diseases, especially oral cancer. Here, we sought to apply multiplexed LC-MRM-MS to precisely quantify 90 disease-related proteins and assess their intra- and inter-individual variability in saliva samples from healthy donors. EXPERIMENTAL DESIGN: We developed two multiplexed LC-MRM-MS assays for 122 surrogate peptides representing a set of disease-related proteins. Saliva samples were collected from 10 healthy volunteers at three different time points (Day 1 morning and afternoon, and Day 2 morning)...
January 19, 2018: Proteomics. Clinical Applications
Sachio Tsuchida, Mamoru Satoh, Hiroshi Umemura, Kazuyuki Sogawa, Masaki Takiwaki, Takayuki Ishige, Yui Miyabayashi, Yuuya Iwasawa, Sohei Kobayashi, Minako Beppu, Motoi Nishimura, Yoshio Kodera, Kazuyuki Matsushita, Fumio Nomura
PURPOSE: Human serum and plasma are often used as clinical specimens in proteomics analyses, and peptidome profiling of human serum is a promising tool for identifying novel disease-associated biomarkers. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is widely used for peptidomic biomarker discovery. Careful sample collection and handling are required as either can have a profound impact on serum peptidome patterns, yet the effects of preanalytical variables on serum peptidome profiles have not been completely elucidated...
January 19, 2018: Proteomics. Clinical Applications
Yogesh M Kulkarni, Sucharita Dutta, Anand Krishnan V Iyer, Clayton A Wright, Vani Ramesh, Vivek Kaushik, Oliver John Semmes, Neelam Azad
PURPOSE: Poor molecular characterization of idiopathic pulmonary fibrosis (IPF) has led to insufficient understanding of the pathogenesis of the disease, resulting in lack of effective therapies and poor prognosis. Particularly, the role of lipid imbalance due to impaired lipid metabolism in the pathogenesis of IPF has been poorly studied. EXPERIMENTAL DESIGN: We have used shotgun lipidomics in a bleomycin (BLM) mouse model of pulmonary fibrosis with vascular endothelial growth factor (VEGF)-inhibitor CBO-P11 as a therapeutic measure, to identify a comprehensive set of lipids that contribute to the pathogenesis of pulmonary fibrosis...
December 28, 2017: Proteomics. Clinical Applications
Apoorva Venkatesh, Concha Gil, Manuel Fuentes, Joshua LaBaer, Sanjeeva Srivastava
Pneumonia, HIV/AIDS, tuberculosis, malaria and several other diseases caused by pathogens largely contribute to the enormous burden of infectious diseases. Over the last few decades, the impact of infectious diseases on a population has been drastic and remains a major health concern even today. Despite advances in science and technology in this era of health and development, there is a substantial knowledge gap in our understanding of the molecular basis of these infectious diseases. The availability of valuable genomic information for a number of pathogens and their hosts has improved our understanding of disease pathogenesis but has not always been useful in addressing important biological questions...
December 28, 2017: Proteomics. Clinical Applications
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