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Clinical Proteomics

Sung Ho Yun, Edmond Changkyun Park, Sang-Yeop Lee, Hayoung Lee, Chi-Won Choi, Yoon-Sun Yi, Hyun-Joo Ro, Je Chul Lee, Sangmi Jun, Hye-Yeon Kim, Gun-Hwa Kim, Seung Il Kim
Background: Outer membrane vesicles (OMVs) of Acinetobacter baumannii are cytotoxic and elicit a potent innate immune response. OMVs were first identified in A. baumannii DU202, an extensively drug-resistant clinical strain. Herein, we investigated protein components of A. baumannii DU202 OMVs following antibiotic treatment by proteogenomic analysis. Methods: Purified OMVs from A. baumannii DU202 grown in different antibiotic culture conditions were screened for pathogenic and immunogenic effects, and subjected to quantitative proteomic analysis by one-dimensional electrophoresis and liquid chromatography combined with tandem mass spectrometry (1DE-LC-MS/MS)...
2018: Clinical Proteomics
Xin Liu, Gensheng Liu, Juan Liu, Peng Zhu, Jiahui Wang, Yanwei Wang, Wenting Wang, Ning Li, Xuebo Wang, Chenglin Zhang, Xiaofang Shen, Fujun Liu
Background: In the assisted reproduction, the infertile molecules of spermatozoa from normozoospermic men who underwent the unexplained failure of in vitro fertilization (IVF) due to the lack of sperm binding to the normal zona pellucida, and then achieved pregnancy with the rescue intracytoplasmic sperm injection (R-ICSI) remain unclear. More works are still necessary to explore this male infertile mechanism. Methods: Normozoospermicmen with the IVF pregnancy and normozoospermic men with the R-ICSI pregnancy after the conventional IVF failure were collected...
2018: Clinical Proteomics
Paul D Piehowski, Vladislav A Petyuk, Ryan L Sontag, Marina A Gritsenko, Karl K Weitz, Thomas L Fillmore, Jamie Moon, Hala Makhlouf, Rodrigo F Chuaqui, Emily S Boja, Henry Rodriguez, Jerry S H Lee, Richard D Smith, Danielle M Carrick, Tao Liu, Karin D Rodland
Background: Mass spectrometry-based proteomics has become a powerful tool for the identification and quantification of proteins from a wide variety of biological specimens. To date, the majority of studies utilizing tissue samples have been carried out on prospectively collected fresh frozen or optimal cutting temperature (OCT) embedded specimens. However, such specimens are often difficult to obtain, in limited in supply, and clinical information and outcomes on patients are inherently delayed as compared to banked samples...
2018: Clinical Proteomics
Vanessa Drendel, Bianca Heckelmann, Christoph Schell, Lucas Kook, Martin L Biniossek, Martin Werner, Cordula A Jilg, Oliver Schilling
Background: Renal oncocytomas (ROs) are benign epithelial tumors of the kidney whereas chromophobe renal cell carcinoma (chRCCs) are malignant renal tumors. The latter constitute 5-7% of renal neoplasias. ROs and chRCCs show pronounced molecular and histological similarities, which renders their differentiation demanding. We aimed for the differential proteome profiling of ROs and early-stage chRCCs in order to better understand distinguishing protein patterns. Methods: We employed formalin-fixed, paraffin-embedded samples (six RO cases, six chRCC cases) together with isotopic triplex dimethylation and a pooled reference standard to enable cohort-wide quantitative comparison...
2018: Clinical Proteomics
Antti Jylhä, Janika Nättinen, Ulla Aapola, Alexandra Mikhailova, Matti Nykter, Lei Zhou, Roger Beuerman, Hannu Uusitalo
Background: Advances in mass spectrometry have accelerated biomarker discovery in many areas of medicine. The purpose of this study was to compare two mass spectrometry (MS) methods, isobaric tags for relative and absolute quantitation (iTRAQ) and sequential window acquisition of all theoretical fragment ion spectra (SWATH), for analytical efficiency in biomarker discovery when there are multiple methodological constraints such as limited sample size and several time points for each patient to be analyzed...
2018: Clinical Proteomics
Andrea Padoan, Daniela Basso, Carlo-Federico Zambon, Tommaso Prayer-Galetti, Giorgio Arrigoni, Dania Bozzato, Stefania Moz, Filiberto Zattoni, Rino Bellocco, Mario Plebani
Background: Lower urinary tract symptoms (LUTS) and prostate specific antigen-based parameters seem to have only a limited utility for the differential diagnosis of prostate cancer (PCa). MALDI-TOF/MS peptidomic profiling could be a useful diagnostic tool for biomarker discovery, although reproducibility issues have limited its applicability until now. The current study aimed to evaluate a new MALDI-TOF/MS candidate biomarker. Methods: Within- and between-subject variability of MALDI-TOF/MS-based peptidomic urine and serum analyses were evaluated in 20 and 15 healthy donors, respectively...
2018: Clinical Proteomics
Rita Azevedo, Cristiana Gaiteiro, Andreia Peixoto, Marta Relvas-Santos, Luís Lima, Lúcio Lara Santos, José Alexandre Ferreira
CD44 is a heavily glycosylated membrane receptor playing a key role in cell adhesion, signal transduction and cytoskeleton remodelling. It is also one of the most studied glycoproteins in cancer, frequently explored for stem cell identification, and associated with chemoresistance and metastasis. However, CD44 is a general designation for a large family of splicing variants exhibiting different degrees of glycosylation and, potentially, functionally distinct roles. Moreover, structural diversity associated with ambiguous nomenclature has delayed clinical developments...
2018: Clinical Proteomics
Xinyan Wu, Muhammad Saddiq Zahari, Santosh Renuse, Nandini A Sahasrabuddhe, Raghothama Chaerkady, Min-Sik Kim, Mary Jo Fackler, Martha Stampfer, Edward Gabrielson, Saraswati Sukumar, Akhilesh Pandey
Background: Cancer-associated fibroblasts (CAFs) are one of the most important components of tumor stroma and play a key role in modulating tumor growth. However, a mechanistic understanding of how CAFs communicate with tumor cells to promote their proliferation and invasion is far from complete. A major reason for this is that most current techniques and model systems do not capture the complexity of signal transduction that occurs between CAFs and tumor cells. Methods: In this study, we employed a stable isotope labeling with amino acids in cell culture (SILAC) strategy to label invasive breast cancer cells, MDA-MB-231, and breast cancer patient-derived CAF this has already been defined above cells...
2018: Clinical Proteomics
Neserin Ali, Stefan Ljunggren, Helen M Karlsson, Aneta Wierzbicka, Joakim Pagels, Christina Isaxon, Anders Gudmundsson, Jenny Rissler, Jörn Nielsen, Christian H Lindh, Monica Kåredal
Background: Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed...
2018: Clinical Proteomics
Ai-Jie Xin, Yan-Cheng Wu, Hui Lu, Li Cheng, Yi-Hua Gu, Hua Diao, Guo-Wu Chen, Bin Wu, Zheng Li, Sheng-Ce Tao, Xiao-Xi Sun, Hui-Juan Shi
Background: Semen cryopreservation has been widely applied in assisted reproductive technologies and sperm bank, but it causes considerable impairments on sperm quality. It is necessary to find an evaluation indicator for determining the sperm-freezing tolerance. Methods: The glycocalyx of good freezability ejaculates was compared with poor freezability ejaculates by lectin microarray. The significant different lectins were validated by flow cytometry (FACS). To analyze the relationship between the potential biomarker and the tolerance of sperm to cryopreservation, 60 samples with different recovery rates were collected and detected the lectin-binding intensity by FACS...
2018: Clinical Proteomics
Feiyu Shi, Hong Wu, Kai Qu, Qi Sun, Fanni Li, Chengxin Shi, Yaguang Li, Xiaofan Xiong, Qian Qin, Tianyu Yu, Xin Jin, Liang Cheng, Qingxia Wei, Yingchao Li, Junjun She
Background: The development of clinically accessible biomarkers is critical for the early diagnosis of gastric cancer (GC) in patients. High-throughput proteomics techniques could not only effectively generate a serum peptide profile but also provide a new approach to identify potentially diagnostic and prognostic biomarkers for cancer patients. Methods: In this study, we aim to identify potentially discriminating serum biomarkers for GC. In the discovery cohort, we screened potential biomarkers using magnetic-bead-based purification and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in 64 samples from 32 GC patients that were taken both pre- and post-operatively and 30 healthy volunteers that served as controls...
2018: Clinical Proteomics
Misol Do, Dohyun Han, Joseph Injae Wang, Hyunsoo Kim, Wooil Kwon, Youngmin Han, Jin-Young Jang, Youngsoo Kim
Background: The application of advanced imaging technologies for identifying pancreatic cysts has become widespread. However, accurately differentiating between low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive intraductal papillary mucinous neoplasms (IPMNs) remains a diagnostic challenge with current biomarkers, necessitating the development of novel biomarkers that can distinguish IPMN malignancy. Methods: Cyst fluid samples were collected from nine IPMN patients (3 LGD, 3 HGD, and 3 invasive IPMN) during their pancreatectomies...
2018: Clinical Proteomics
Anaïs Chauvin, Chang-Shu Wang, Sameh Geha, Perrine Garde-Granger, Alex-Ane Mathieu, Vincent Lacasse, François-Michel Boisvert
Background: Colorectal cancer is the third most common and the fourth most lethal cancer in the world. In the majority of cases, patients are diagnosed at an advanced stage or even metastatic, thus explaining the high mortality. The standard treatment for patients with locally advanced non-metastatic rectal cancer is neoadjuvant radio-chemotherapy (NRCT) with 5-fluorouracil (5-FU) followed by surgery, but the resistance rate to this treatment remains high with approximately 30% of non-responders...
2018: Clinical Proteomics
Julien Peltier, Jean-Pierre Roperch, Stéphane Audebert, Jean-Paul Borg, Luc Camoin
Background: Colorectal cancer (CRC) remains a major cause of cancer fatalities in developed countries. The risk of death is correlated to the stage of CRC during the primary diagnosis. Early diagnosis is closely associated with enhanced survival rate. We therefore investigated the AP-F13A1 as a potential protein marker of CRC. Methods: The protein expression of FXIII in 40 serum samples was evaluated by enzyme-linked immunosorbent assays. Additionally, targeted proteomic assays (LC-PRM) were used to evaluate the expression of the activation peptide of F13A1 (AP-F13A1) in a further 113 serum samples...
2018: Clinical Proteomics
Haddy K S Fye, Paul Mrosso, Lesley Bruce, Marie-Laëtitia Thézénas, Simon Davis, Roman Fischer, Gration L Rwegasira, Julie Makani, Benedikt M Kessler
Background: Red blood cell (RBC) physiology is directly linked to many human disorders associated with low tissue oxygen levels or anemia including chronic obstructive pulmonary disease, congenital heart disease, sleep apnea and sickle cell anemia. Parasites such as Plasmodium spp. and phylum Apicomplexa directly target RBCs, and surface molecules within the RBC membrane are critical for pathogen interactions. Proteomics of RBC membrane 'ghost' fractions has therefore been of considerable interest, but protocols described to date are either suboptimal or too extensive to be applicable to a larger set of clinical cohorts...
2018: Clinical Proteomics
Nina Zila, Andrea Bileck, Besnik Muqaku, Lukas Janker, Ossia M Eichhoff, Phil F Cheng, Reinhard Dummer, Mitchell P Levesque, Christopher Gerner, Verena Paulitschke
Background: MAP kinase inhibitor (MAPKi) therapy for BRAF mutated melanoma is characterized by high response rates but development of drug resistance within a median progression-free survival (PFS) of 9-12 months. Understanding mechanisms of resistance and identifying effective therapeutic alternatives is one of the most important scientific challenges in melanoma. Using proteomics, we want to specifically gain insight into the pathophysiological process of cerebral metastases. Methods: Cerebral metastases from melanoma patients were initially analyzed by a LC-MS shotgun approach performed on a QExactive HF hybrid quadrupole-orbitrap mass spectrometer...
2018: Clinical Proteomics
Chen Zou, Changjing Han, Minjie Zhao, Jingjing Yu, Lin Bai, Yuan Yao, Shuaixin Gao, Hui Cao, Zhi Zheng
Background: Preoperative treatment of anti-vascular endothelial growth factor (VEGF) agents is extensively used in proliferative diabetic retinopathy (PDR), but the molecular mechanism is not fully understood. The objective of this research is to observe change of protein profile induced by ranibizumab (an anti-VEGF agent) in vitreous humor from PDR patients and reveal the effects of anti-VEGF treatment on PDR. Methods: A proteomic method was used to identify differentially expressed proteins in vitreous humor...
2018: Clinical Proteomics
Melanie Christine Föll, Matthias Fahrner, Victor Oginga Oria, Markus Kühs, Martin Lothar Biniossek, Martin Werner, Peter Bronsert, Oliver Schilling
Background: Proteomic analyses of clinical specimens often rely on human tissues preserved through formalin-fixation and paraffin embedding (FFPE). Minimal sample consumption is the key to preserve the integrity of pathological archives but also to deal with minimal invasive core biopsies. This has been achieved by using the acid-labile surfactant RapiGest in combination with a direct trypsinization (DTR) strategy. A critical comparison of the DTR protocol with the most commonly used filter aided sample preparation (FASP) protocol is lacking...
2018: Clinical Proteomics
Prahlad K Rao, Kate Merath, Eugene Drigalenko, Avinash Y L Jadhav, Richard A Komorowski, Matthew I Goldblatt, Anand Rohatgi, Mark A Sarzynski, Samer Gawrieh, Michael Olivier
Background: Metabolic diseases such as obesity and diabetes are associated with changes in high-density lipoprotein (HDL) particles, including changes in particle size and protein composition, often resulting in abnormal function. Recent studies suggested that patients with non-alcoholic fatty liver disease (NAFLD), including individuals with non-alcoholic steatohepatitis (NASH), have smaller HDL particles when compared to individuals without liver pathologies. However, no studies have investigated potential changes in HDL particle protein composition in patients with NAFLD, in addition to changes related to obesity, to explore putative functional changes of HDL which may increase the risk of cardiovascular complications...
2018: Clinical Proteomics
Qianqian Zhao, Tiancheng Zhan, Zaian Deng, Qianqian Li, Yaming Liu, Shaojie Yang, Dengbo Ji, Yan Li
Background: Carcinoembryonic antigen (CEA) is a glycoprotein associated with colorectal cancer (CRC). While the functions of its gene and protein have been fully characterized, its post-translational modifications in the context of CRC development remain undefined. Methods: To show the correlation between the different stages of CRC development and changes in the glycosylation patterns of CEA, we analyzed CEA in tumor tissues (CEA-T) and paired tumor-adjacent normal tissues (CEA-A) from 53 colorectal cancer patients using a high-density lectin microarray containing 56 plant lectins...
2018: Clinical Proteomics
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