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      Human Pituitary Adenoma Proteomics: New Progresses and Perspectives

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          Abstract

          Pituitary adenoma (PA) is a common intracranial neoplasm that impacts on human health through interfering hypothalamus–pituitary–target organ axis systems. The development of proteomics gives great promises in the clarification of molecular mechanisms of a PA and discovery of effective biomarkers for prediction, prevention, early-stage diagnosis, and treatment for a PA. A great progress in the field of PA proteomics has been made in the past 10 years, including (i) the use of laser-capture microdissection, (ii) proteomics analyses of functional PAs (such as prolactinoma), invasive and non-invasive non-functional pituitary adenomas (NFPAs), protein post-translational modifications such as phosphorylation and tyrosine nitration, NFPA heterogeneity, and hormone isoforms, (iii) the use of protein antibody array, (iv) serum proteomics and peptidomics, (v) the integration of proteomics and other omics data, and (vi) the proposal of multi-parameter systematic strategy for a PA. This review will summarize these progresses of proteomics in PAs, point out the existing drawbacks, propose the future research directions, and address the clinical relevance of PA proteomics data, in order to achieve our long-term goal that is use of proteomics to clarify molecular mechanisms, construct molecular networks, and discover effective biomarkers.

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          Most cited references82

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          Recent analyses of sequence and microarray data have suggested that alternative splicing plays a major role in the generation of proteomic and functional diversity in metazoan organisms. Efforts are now being directed at establishing the full repertoire of functionally relevant transcript variants generated by alternative splicing, the specific roles of such variants in normal and disease physiology, and how alternative splicing is coordinated on a global level to achieve cell- and tissue-specific functions. Recent progress in these areas is summarized in this review.
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            Protein kinase inhibitors: insights into drug design from structure.

            Protein kinases are targets for treatment of a number of diseases. This review focuses on kinase inhibitors that are in the clinic or in clinical trials and for which structural information is available. Structures have informed drug design and have illuminated the mechanism of inhibition. We review progress with the receptor tyrosine kinases (growth factor receptors EGFR, VEGFR, and FGFR) and nonreceptor tyrosine kinases (Bcr-Abl), where advances have been made with cancer therapeutic agents such as Herceptin and Gleevec. Among the serine-threonine kinases, p38, Rho-kinase, cyclin-dependent kinases, and Chk1 have been targeted with productive results for inflammation and cancer. Structures have provided insights into targeting the inactive or active form of the kinase, for targeting the global constellation of residues at the ATP site or less conserved additional pockets or single residues, and into targeting noncatalytic domains.
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              Laser capture microdissection.

              Laser capture microdissection (LCM) under direct microscopic visualization permits rapid one-step procurement of selected human cell populations from a section of complex, heterogeneous tissue. In this technique, a transparent thermoplastic film (ethylene vinyl acetate polymer) is applied to the surface of the tissue section on a standard glass histopathology slide; a carbon dioxide laser pulse then specifically activates the film above the cells of interest. Strong focal adhesion allows selective procurement of the targeted cells. Multiple examples of LCM transfer and tissue analysis, including polymerase chain reaction amplification of DNA and RNA, and enzyme recovery from transferred tissue are demonstrated.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                31 May 2016
                2016
                : 7
                : 54
                Affiliations
                [1] 1Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University , Changsha, China
                [2] 2Hunan Engineering Laboratory for Structural Biology and Drug Design, Xiangya Hospital, Central South University , Changsha, China
                [3] 3State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University , Changsha, China
                [4] 4The State Key Laboratory of Medical Genetics, Central South University , Changsha, China
                Author notes

                Edited by: Carmen E. Georgescu, Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoc, Romania

                Reviewed by: Laurence Katznelson, Stanford University, USA; Hidenori Fukuoka, Kobe University Hospital, Japan

                *Correspondence: Xianquan Zhan, yjzhan2011@ 123456gmail.com

                Specialty section: This article was submitted to Pituitary Endocrinology, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2016.00054
                4885873
                27303365
                7088232b-ae61-45e8-bcae-457ace480258
                Copyright © 2016 Zhan, Wang and Cheng.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 March 2016
                : 17 May 2016
                Page count
                Figures: 0, Tables: 2, Equations: 0, References: 92, Pages: 11, Words: 9019
                Funding
                Funded by: China “863” Plan Project
                Award ID: 2014AA020610-1
                Funded by: Xiangya Hospital Funds for Talent Introduction
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81272798 and 81572278
                Funded by: Hunan Provincial Natural Science Foundation of China
                Award ID: 14JJ7008
                Categories
                Endocrinology
                Review

                Endocrinology & Diabetes
                pituitary adenoma,proteome,heterogeneity,reference map,two-dimensional gel electrophoresis,mass spectrometry,bioinformatics

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