HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Glossary Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                      What's this?

Molecular & Cellular Proteomics 6:S67, 2007.
© 2007 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Abstracts

Session 8

Exploration of the Human Muscle Proteome in Diabetes

S. Weintraub¹, C. A. Carroll^1,2, S. Kamath², A. Monroy², A. O. Chavez-Velazquez², R. A. DeFronzo², F. Folli²

¹Department of Biochemistry and ²Diabetes Division, Department of Medicine, University of Texas Health Science Center, San Antonio, TX

PLEASE SEE PROGRAM ADDENDUM FOR ABSTRACT.

8.2

Protein Biomarker Identification in the Cerebrospinal Fluid in Patients with Central Nervous System Lymphoma

S. Roy¹, S. A. Josephson², J. Fridlyand³, J. Karch⁴, C. Kadoch⁴, J. Karrim⁴, L. Damon⁴, P. Treseler⁵, S. Kunwar⁶, M. A. Shuman⁴, T. Jones¹, C. H. Becker¹, H. Schulman¹, J. L. Rubenstein⁴

¹PPD Biomarkers, Menlo Park, CA; Departments of ²Neurology, ³Epidemiology and Biostatistics, ⁴Medicine, ⁵Pathology, and ⁶Neurological Surgery, University of California, San Francisco, CA

Purpose: Elucidation of the cerebrospinal fluid (CSF) proteome may yield insights into the pathogenesis of central nervous system (CNS) disease. We tested the hypothesis that individual CSF proteins distinguish CNS lymphoma from benign focal brain lesions.

Methods: We used a liquid chromatography-mass spectrometry-based method to differentially quantify and identify several hundred CSF proteins in CNS lymphoma and control patients. We used ELISA to confirm results for one of these markers in an additional validation set of 101 cases.

Results: Approximately 80 CSF proteins were identified and found to be present at significantly different concentrations, both higher and lower, in training and test studies which were highly concordant. To further validate these observations, we defined in detail the expression of one of these candidate biomarkers, a serine protease inhibitor, AT. AT RNA transcripts were identified within CNS lymphomas and AT protein was localized selectively to tumor neovasculature. Determination of AT concentration by ELISA was significantly more accurate (>75% sensitivity; >98% specificity) than cytology in the identification of cancer. Measurement of CSF AT levels was found to potentially enhance the ability to diagnose and predict outcome.

Conclusion: Our findings demonstrate for the first time that proteomic analysis of the CSF yields individual biomarkers with greater sensitivity than CSF cytology in the identification of cancer. We propose that the discovery of CSF protein biomarkers will facilitate early and noninvasive diagnosis in patients with lesions not amenable to brain biopsy as well as provide improved surrogates of prognosis and treatment response.

8.3

Progress Toward a Biomarker Discovery-to-Verification Pipeline in Clinical Proteomics

S. A. Carr

Proteomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA

Better biomarkers are urgently needed to improve diagnosis, guide molecularly targeted therapy, and monitor activity and therapeutic response across a wide spectrum of disease. Proteomics methods based on mass spectrometry hold special promise for the discovery of novel biomarkers that might form the foundation for new clinical blood tests, but to date their contribution to the diagnostic armamentarium has been disappointing. This is due in part to the lack of a coherent pipeline connecting marker discovery with well established methods for validation. Advances in methods and technology now enable construction of a comprehensive biomarker pipeline from six essential process components: candidate discovery, qualification, verification, research assay optimization, biomarker validation, and commercialization. Better understanding of the overall process of biomarker discovery and validation and of the challenges and strategies inherent in each phase should improve experimental study design, in turn increasing the efficiency of biomarker development and facilitating the delivery and deployment of novel clinical tests. In this talk I will illustrate discovery-through-quantitative verification steps with examples from our ongoing studies in breast cancer and cardiovascular disease.

8.4

The Protein Microscope: An Application of Cell Map Proteomics

J. Bergeron

Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada

The application of hierarchical clustering to a quantitative representation of comprehensive protein abundance in isolated organelles provides a ready method to sort contaminants from resident proteins and gain insight into organelle identity and function. Organelle based proteomics provides hundreds of proteins of unknown function. An application of the protein microscope is to assign locations and mechanistic functions to these proteins.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This Article Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Glossary Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                      What's this?