共查询到20条相似文献，搜索用时 15 毫秒
1.
Signaling molecules released by adipose tissue have been implicated in inflammation, adipocyte dysfunction and systemic insulin resistance. In this study, we used 2-D LC-MS/MS and quantitative proteomics approaches to characterize the obese adipose secretory proteins that are responsive to the thiazolidinediones class of PPAR-γ agonizts. We first showed the differential secretion profiling between obese and lean adipose tissue; 87 proteins were detected from the conditioned medium of adipose tissue of Zucker obese rats compared with 31 from lean rats. A total of 57 proteins comprising immune factors, inflammatory molecules, collagens, proteases, and extracellular matrix proteins were detected from obese, but not lean adipose tissue. More importantly, a quantitative proteomics approach using (18) O proteolytic labeling allowed quantification of the difference in the secretion levels of 77 proteins, and thiazolidinediones treatment suppressed the secretion of most of the obese adipose tissue secretome, thus resembling a lean tissue. We have demonstrated an application of identifying the obese adipose secretome and characterizing the regulation of adipose secretion in obesity and insulin resistance. Our data provide the first evidence of changes in adipose secretion in obesity at a global level and show that such changes are correlated with systemic insulin resistance. 相似文献
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Wei Sun Yong Chen Fuxin Li Ling Zhang Ruifeng Yang Zhi Zhang Dexian Zheng Youhe Gao Professor 《Proteomics. Clinical applications》2009,3(3):370-382
Human urinary proteome analysis is a convenient and efficient approach for understanding disease processes affecting the kidney and urogenital tract. Many potential biomarkers have been identified in previous differential analyses; however, dynamic variations of the urinary proteome have not been intensively studied, and it is difficult to conclude that potential biomarkers are genuinely associated with disease rather then simply being physiological proteome variations. In this paper, pooled and individual urine samples were used to analyze dynamic variations in the urinary proteome. Five types of pooled samples (first morning void, second morning void, excessive water‐drinking void, random void, and 24 h void) collected in 1 day from six volunteers were used to analyze intra‐day variations. Six pairs of first morning voids collected a week apart were used to study inter‐day, inter‐individual, and inter‐gender variations. The intra‐day, inter‐day, inter‐individual, and inter‐gender variation analyses showed that many proteins were constantly present with relatively stable abundances, and some of these had earlier been reported as potential disease biomarkers. In terms of sensitivity, the main components of the five intra‐day urinary proteomes were similar, and the second morning void is recommended for clinical proteome analysis. The advantages and disadvantages of pooling samples are also discussed. The data presented describe a pool of stable urinary proteins seen under different physiological conditions. Any significant qualitative or quantitative changes in these stable proteins may mean that such proteins could serve as potential urinary biomarkers. 相似文献
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Moshkovskii SA Vlasova MA Pyatnitskiy MA Tikhonova OV Safarova MR Makarov OV Archakov AI 《Proteomics. Clinical applications》2007,1(1):107-117
In the context of serum amyloid A (SAA) identification as ovarian cancer marker derived by SELDI‐MS, its serum levels were measured by immunoassay in different stages of ovarian cancer, in benign gynecological tumors, and in healthy controls. In addition, SELDI‐TOF‐MS spectra were obtained by protocol optimized for the SAA peak intensity. SELDI data on small proteins (5.5–17.5 kDa) and SAA immunoassay data were combined with cancer antigen (CA)125 data in order to study the classification accuracy between cancer and noncancer by support vector machine (SVM), logistic regression, and top scoring pair classifiers. Although an addition of SAA immunoassay data to CA125 data did not significantly improve cancer/noncancer discrimination, SVM applied to combined biomarker data (CA125 and SAA immunoassay variables plus 48 SELDI peak variables) yielded the best classification rate (accuracy 95.2% vs. 86.2% for CA125 alone). Notably, most of discriminatory peaks selected by the classifiers have significant correlation with the major known peaks of SAA (11.7 kDa) and transthyretin (13.9 kDa). Acute phase serum amyloid A (A‐SAA) was proved to be an important member of cancer discriminatory protein profile. Among the eight known ovarian cancer SELDI profile components, A‐SAA is the most relevant to molecular pathogenesis of cancer and it has the highest degree of up‐regulation in disease. 相似文献
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Tadashi Kondo Yoshiyuki Suehara Kazutaka Kikuta Daisuke Kubota Takashi Tajima Kenta Mukaihara Hiroshi Ichikawa Akira Kawai 《Proteomics. Clinical applications》2013,7(1-2):70-78
Sarcomas range from curable tumors to those causing death via metastasis and recurrence. Thus, there is an urgent need for biomarker identification in order to assess the degree of malignancy, predict prognosis, and evaluate possible therapies. Various proteomic approaches and different clinical materials have been used to this end, and candidate biomarkers have been reported for the different types of sarcomas. However, the sample size used in these biomarker studies was generally insufficient, and thus far, no biomarker has been proved useful in clinics. Given that sarcomas are rare, biomarker validation in this setting is more challenging than in other malignancies. In gastrointestinal stromal tumor, adjuvant therapy has proven to be effective. However, only 40% patients experience metastasis after curative surgery alone, and the rest of the patients may not need adjuvant therapy. Using a proteomic approach, we identified pfetin (potassium channel tetramerization domain containing 12, KCTD 12) as a novel prognostic biomarker for sarcoma, and immunohistochemically confirmed its clinical usefulness by a multiinstitutional validation study. Here, we describe our experience and discuss the critical points in the discovery of this biomarker. 相似文献
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Colorectal cancer (CRC) arises from the normal colon epithelium through the accumulation of genetic mutations and epigenetic alterations that are associated with progression along the histological adenoma-adenocarcinoma sequence. Elucidating the molecular alterations underlying disease progression will not only provide insight into the behavior of the tumors, but also could lead to the discovery of useful biomarkers for diagnosis, monitoring treatment responsiveness, or predicting disease outcomes. In the past a few years, there have been several evaluating differentially expressed protein biomarkers by employing proteomics technologies coupled with mass spectrometry. In the current review, we will briefly summarize the results from selected recent studies using tissue or serum samples from CRC patients in the past 5 years and discuss the opportunities and challenges in translating these findings from the research setting to clinical practice. 相似文献
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Parul Mittal Manuela Klingler‐Hoffmann Georgia Arentz Chao Zhang Gurjeet Kaur Martin K. Oehler Peter Hoffmann 《Proteomics. Clinical applications》2016,10(3):217-229
This review discusses the current status of proteomics technology in endometrial cancer diagnosis, treatment and prognosis. The first part of this review focuses on recently identified biomarkers for endometrial cancer, their importance in clinical use as well as the proteomic methods used in their discovery. The second part highlights some of the emerging mass spectrometry based proteomic technologies that promise to contribute to a better understanding of endometrial cancer by comparing the abundance of hundreds or thousands of proteins simultaneously. 相似文献
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Cancer cell lines are the most widely used experimental models in cancer research. Their advantages of easy growth and manipulation are unfortunately paralleled by their limitations derived from long-term growth in isolation from the rest of the tumor, and hence, lack of tumor microenvironment. We are however currently witnessing novel and transformative advances that are making cell lines more reflective of the human biology and therefore, better experimental models for cancer research. Beyond the experimental model used, the choice of cellular proteome is key in proteomics-based biomarker discovery. Over the last decade, cell line secretomes have been proposed as an alternative for tumor biomarker discovery due to the difficulties posed by plasma in terms of complexity and low abundance of tumor-specific biomarkers. Cell line secretomes are enriched with proteins already linked to tumorigenesis, which also have a good chance of being present in biological fluids. In this review, we will provide an overview of the main technical and biological issues related to cell line secretome analysis, and briefly discuss both the challenges and opportunities in its use for tumor biomarker discovery. 相似文献
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Daniel Martins‐de‐Souza 《Proteomics. Clinical applications》2009,3(10):1136-1139
The relatively young science of proteomics has been extensively used to identify biomarkers. However, a detailed and careful interpretation of proteomics data can also provide a clear picture of integrated biochemical systems, which can lead to a better comprehension of pathological processes. For example, the proteome analysis of human brain tissue from patients with schizophrenia, bipolar disorder, or multiple sclerosis compared with healthy controls has identified differentially expressed proteins that may not only be potential biomarkers but may also provide information that may increase the comprehension of these neurological disorders. Thus, proteomics is not only a biomarker discovery tool but can also identify potential players of relevance for diseases. 相似文献
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Gülgün Tezel 《Proteomics. Clinical applications》2014,8(3-4):154-167
Glaucoma is a leading cause of blindness; however, limited understanding of the molecular mechanisms involved in optic nerve degeneration hinders the development of improved treatment strategies. Proteomics techniques that combine the protein chemistry, MS, and bioinformatics offer the opportunity to shed light on molecular mechanisms so that new treatment strategies can be developed for immunomodulation, neuroprotection, neurorescue, neuroregeneration, and function gain in glaucoma. The proteomics technologies also hold great promise for biomarker discovery, another important goal of glaucoma research. As much as developing new treatment strategies, molecular biomarkers are strongly needed for early diagnosis of glaucoma, prediction of its prognosis, and monitoring the responses to new treatments. It is now a decade that the proteomics analysis techniques have been using to move glaucoma research forward. This review will focus on valuable applications of proteomics in the field of glaucoma research and highlight the power of this analytical toolbox in translational and clinical research toward better characterization and improved treatment of glaucomatous neurodegeneration and discovery of glaucoma-related molecular biomarkers. 相似文献
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This report reviews the 5th US HUPO annual conference which was held in San Diego, California, from 22th to 25th February, 2009. The major goal of this year's meeting was to discuss future prospects within the field of proteomics and to push it towards integration with other synergizing technologies. Each day's sessions were guided by three broad themes: The Interface of Proteomics and Genomics, Systems Medicine, and Protein Structure and Modifications. As a summary this meeting has shown, that integration of multiple disciplines and high performance proteomics is needed to meet the demands of future proteomics. 相似文献
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Iosif Vranakis Anastasia Papadioti Yannis Tselentis Anna Psaroulaki Georgios Tsiotis 《Proteomics. Clinical applications》2013,7(1-2):193-204
Coxiella burnetii, the causative agent of Q fever, is an intracellular bacterium and a potential weapon for bioterrorism. The widespread throughout the world, zoonosis is manifested clinically as a self-limited febrile illness, as pneumonia (acute Q fever) or as a chronic illness with endocarditis being its major complication. The recent Netherlands Q fever outbreak has driven the bacterium from a relatively cryptic, underappreciated, “niche” microorganism on the sideline of bacteriology, to one of possibly great impact on public health. Advances in the study of this microorganism proceeded slowly, primarily due to the, until recently, obligatory intracellular nature of the pathogen that in its virulent phase I must be manipulated under biosafety level-3 conditions. Proteomic studies, in particular, have generated a vast amount of information concerning several aspects of the bacterium such as virulence factors, detection/diagnostic and immunogenic biomarkers, inter-/intraspecies variation, resistance to antibiotics, and secreted effector proteins with significant clinical impact. The phenomenon observed following the genomics era, that of generation and accumulation of huge amount of data that ultimately end up unexploited on several databases, begins to emerge in the proteomics field as well. This review will focus on the advances in the field of C. burnetii proteomics through MS, attempting in parallel to utilize some of the proteomics findings by suggesting future directions for the improvement of Q fever diagnosis and therapy. 相似文献
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Kentsis A Monigatti F Dorff K Campagne F Bachur R Steen H 《Proteomics. Clinical applications》2009,3(9):1052-1061
Knowledge of the biologically relevant components of human tissues has enabled the invention of numerous clinically useful diagnostic tests, as well as non-invasive ways of monitoring disease and its response to treatment. Recent use of advanced MS-based proteomics revealed that the composition of human urine is more complex than anticipated. Here, we extend the current characterization of the human urinary proteome by extensively fractionating urine using ultra-centrifugation, gel electrophoresis, ion exchange and reverse-phase chromatography, effectively reducing mixture complexity while minimizing loss of material. By using high-accuracy mass measurements of the linear ion trap-Orbitrap mass spectrometer and LC-MS/MS of peptides generated from such extensively fractionated specimens, we identified 2362 proteins in routinely collected individual urine specimens, including more than 1000 proteins not described in previous studies. Many of these are biomedically significant molecules, including glomerularly filtered cytokines and shed cell surface molecules, as well as renally and urogenitally produced transporters and structural proteins. Annotation of the identified proteome reveals distinct patterns of enrichment, consistent with previously described specific physiologic mechanisms, including 336 proteins that appear to be expressed by a variety of distal organs and glomerularly filtered from serum. Comparison of the proteomes identified from 12 individual specimens revealed a subset of generally invariant proteins, as well as individually variable ones, suggesting that our approach may be used to study individual differences in age, physiologic state and clinical condition. Consistent with this, annotation of the identified proteome by using machine learning and text mining exposed possible associations with 27 common and more than 500 rare human diseases, establishing a widely useful resource for the study of human pathophysiology and biomarker discovery. 相似文献
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Li J Abraham S Cheng L Witzmann FA Koch M Xie J Rahman M Mohammed SI 《Proteomics. Clinical applications》2008,2(1):78-89
Identification of reliable non-invasive markers for the detection of invasive phenotype of urothelial carcinoma is needed. This study characterizes and compares protein expression profiles of adjacent non-neoplastic urothelium and invasive urothelial carcinoma to identify biomarkers for early detection of de novo bladder cancer. Differences in protein expression between adjacent non-neoplastic and high-grade, stage T4, grade 3 invasive urothelial carcinoma tissues were investigated using 2-DE, MALDI-TOF-MS, and data processing. Ingenuity Pathway Analysis (IPA) was applied to examine the biological mechanisms represented by the altered proteins. The 2-DE of the adjacent non-neoplastic urothelium and invasive urothelial carcinoma showed reproducibly similar proteomic mapping for each group distinguishing adjacent non-neoplastic urothelium from invasive urothelial carcinoma. Twenty-one proteins were altered in expression and one of these proteins, Choroideremia-like protein (CHML) was significantly overexpressed (p<0.005) and therefore was analyzed further using IHC and Western blot. Urothelial carcinoma presented an elevated expression of CHML but not adjacent non-neoplastic or normal bladder tissues. IPA revealed the involvement of CHML in cell morphology, cellular assembly, and organization. Further investigation is warranted to elucidate the biological significance of CHML and to validate its role as a biomarker for early detection of invasive urothelial carcinoma de novo. 相似文献
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Sergej Skvortsov Christoph R. Arnold Paul Debbage Peter Lukas Ira Skvortsova 《Proteomics. Clinical applications》2015,9(11-12):1069-1077
The majority of tumor-related deaths are due to metastasis. Despite the clinical importance of understanding metastasis, we lack knowledge of the molecular mechanisms underlying tumor cell spreading and cell survival far from the primary tumor. Elucidating the molecular characteristics of highly metastatic carcinoma cells would help identify biomarkers or therapeutic targets relevant to predicting or combatting metastasis, and for this the phenotype of metastatic cells could be much more important than their genotype. Hence, proteomic approaches have wide potential utility. This review discusses possibilities of analyzing metastasis-specific protein patterns in a range of sample types, including in vitro and in vivo cancer models, and tissues and biological fluids from patients. Proteome approaches can identify proteins involved in regulating the metastatic capacities of tumors. 相似文献
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Rita Büchler Sindy Wendler Petra Muckova Julian Großkreutz Heidrun Rhode 《Proteomics. Clinical applications》2016,10(11):1073-1076
Several reasons have been put forward to explain the irreproducibility of proteomic biomarker search. However, these reasons pertain to almost every part of biomarker search across the entire analytical workflow but are entirely experimental or methodological. However, in this article we point out that there is a further cause of such irreproducibility. This is not an additional methodological or experimental cause but arises directly from the biology of protein expression. It arises from the fact that disease changes the diversity within protein families. This cause of irreproducibility has been very little studied in relation to proteomic biomarker search. Gene expression is highly variable even in healthy people. Therefore, multiple proteoforms are also to be expected when gene expression is disrupted by disease, proteoforms that may be differently altered by pathology. In consequence, it is illogical to expect that the whole protein family produces a reliably usable biomarker. It is more reasonable to expect that a specific proteoform fulfills this role. Appropriate sample pre‐fractionation methods and data analyses could help to identify this version, carrying the modification or the epitope required. 相似文献
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Qi Wang Chi Wang Jiayu Liu Jingru Sun Chengbin Wang Xuesong Zhang 《Proteomics. Clinical applications》2021,15(4):2100002