Bridging The Knowledge Gap Between Scientists That Develop And Apply Proteomics Technologies And Oncologists Who Focus On Understanding The Biological Basis Behind Cancer Manifestation And Progression, Proteomic Applications In Cancer Detection And Discovery Provides An Up-to-date Account Of How The Multiple Facets Of Proteomics Have Been Applied To Cancer. By Balancing The Treatment Of Technologies And Applications, The Book Enables Analytical Scientists And Oncologists, Post-doctoral Researchers, Major Research Or Medical Centers, Cancer Researchers, Pharmaceutical Researchers, Chemists, And Biologists To Better Understand Both-- Proteomic Applications In Cancer Detection And Discovery; Contents; Preface; Acknowledgments; 1 Systems Biology; 1.1 Introduction; 1.2 What Is Systems Biology?; 1.3 What Systems Do We Need To Study?; 1.3.1 Genomics; 1.3.2 Transcriptomics; 1.3.3 Proteomics; 1.3.4 Metabolomics; 1.4 Cancer Is A Systems Biology Disease; 1.5 Modeling Systems Biology; 1.6 Data Integration; 1.6.1 Integrating Transcriptomics And Proteomics; 1.7 Conclusions; References; 2 Mass Spectrometry Incancer Research; 2.1 Introduction; 2.2 Mass Spectrometry: The Technology Driving Cancerprotein Biomarker Discovery. 2.2.1 Ion Sources2.2.2 Electrospray Ionization; 2.2.3 Matrix-assisted Laser Desorption/ionization; 2.3 Types Of Mass Spectrometers; 2.3.1 Ion-trap Mass Spectrometer; 2.3.2 Fourier Transform Ion Cyclotron Resonance Ms; 2.3.3 Orbitrap Mass Spectrometer; 2.3.4 Tof Mass Spectrometer; 2.3.5 Triple-quadrupole Mass Spectrometer; 2.3.6 Triple-quadrupole Tof Mass Spectrometer; 2.4 Protein Fractionation; 2.4.1 Polyacrylamide Gel Electrophoresis; 2.4.2 Liquid Chromatography; 2.5 Impact Of Ms In Cancer; 2.5.1 Identification Of A Drug Target; 2.6 Conclusions; References; 3 Quantitative Proteomics. 3.1 Introduction3.2 What Is Being Measured In Quantitative Proteomics?; 3.3 Two-dimensional Polyacrylamide Gel Electrophoresis; 3.4 Two-dimensional Difference Gel Electrophoresis; 3.5 Solution-based Quantitative Methods; 3.5.1 Stable Isotope Labeling; 3.5.2 Isotope-coded Affinity Tags; 3.5.3 Isobaric Tag For Relative And Absolute Quantitation; 3.5.4 Stable Isotope Labeling Of Amino Acids In Culture; 3.6 Nonisotopic Solution-based Quantitation; 3.6.1 Subtractive Proteomics-peptide Counting; 3.6.2 Subtractive Proteomics-peak Intensity; 3.7 Conclusions; References. 4 Proteomic Analysis Of Posttranslational Modifications4.1 Introduction; 4.2 Phosphorylation; 4.2.1 Identification Of Phosphorylated Proteins; 4.2.2 Phosphopeptide Mapping; 4.2.3 Collision-induced Dissociation; 4.2.4 Electron Capture And Electron Transfer Dissociation; 4.2.5 Electron Transfer Dissociation; 4.2.6 Enrichment Of Phosphopeptides; 4.2.7 Immunoaffinity Chromatography; 4.2.8 Immobilized Metal Affinity Chromatography; 4.2.9 Metal Oxide Affinity Chromatography; 4.3 Glycosylation; 4.3.1 Mass Spectrometry Characterization; 4.3.2 Electron Capture And Electron Transfer Dissociation. 4.3.3 Targeted Identification Of Glycoproteins4.3.4 Proteome-wide Identification Of Glycoproteins; 4.4 Other Posttranslational Modifications; 4.5 Conclusions; References; 5 Characterization Of Protein Complexes; 5.1 Introduction; 5.2 Methods For Isolating Protein Complexes; 5.2.1 Optimizing Protein Complex Isolation; 5.2.2 Importance Of Optimizing Isolation Conditions; 5.2.3 Oligoprecipitation; 5.3 Proteome Screening Using Tandem Affinity Purification; 5.4 Yeast Two-hybrid Screening; 5.5 Quick Lc-ms Method To Identify Specifically Bound Proteins; 5.6 Protein Arrays. Timothy D. Veenstra, Laboratory Of Proteomics And Analytical Technologies, Advanced Technologies Program, Saic-frederick, Inc., Frederick National Laboratory For Cancer Research. Description Based On Online Resource; Title From Home Page (viewed On May 23, 2014). Includes Bibliographical References And Index.

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nexusstc/Proteomic Applications in Cancer Detection and Discovery/4fd83bccc390a5d9d707ef3cb46361cb.pdf

zlib/Medicine/Timothy Daniel Veenstra/Proteomic applications in cancer detection and discovery_2349967.pdf

The Effective Public Manager Achieving Success in Government Organizations

Veenstra, Timothy D.

Jossey-Bass, Incorporated Publishers

John Wiley & Sons, Incorporated

Wiley & Sons, Limited, John

WILEY COMPUTING Publisher

John Wiley & Sons, Inc., Hoboken, New Jersey, 2013

United States, United States of America

October 2, 2007

1, 2013-07-10

1, 2013-05-30

lg1181507

producers:
Acrobat Distiller 7.0.5 (Windows)

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PROTEOMIC APPLICATIONS IN CANCER DETECTION AND DISCOVERY 3
CONTENTS 7
PREFACE 9
ACKNOWLEDGMENTS 11
1 SYSTEMS BIOLOGY 13
1.1 INTRODUCTION 13
1.2 WHAT IS SYSTEMS BIOLOGY? 15
1.3 WHAT SYSTEMS DO WE NEED TO STUDY? 17
1.3.1 Genomics 19
1.3.2 Transcriptomics 22
1.3.3 Proteomics 24
1.3.4 Metabolomics 26
1.4 CANCER IS A SYSTEMS BIOLOGY DISEASE 28
1.5 MODELING SYSTEMS BIOLOGY 29
1.6 DATA INTEGRATION 30
1.6.1 Integrating Transcriptomics and Proteomics 31
1.7 CONCLUSIONS 33
REFERENCES 34
2 MASS SPECTROMETRY INCANCER RESEARCH 39
2.1 INTRODUCTION 39
2.2 MASS SPECTROMETRY: THE TECHNOLOGY DRIVING CANCERPROTEIN BIOMARKER DISCOVERY 40
2.2.1 Ion Sources 40
2.2.2 Electrospray Ionization 41
2.2.3 Matrix-Assisted Laser Desorption/Ionization 43
2.3 TYPES OF MASS SPECTROMETERS 44
2.3.1 Ion-Trap Mass Spectrometer 46
2.3.2 Fourier Transform Ion Cyclotron Resonance MS 46
2.3.3 Orbitrap Mass Spectrometer 48
2.3.4 TOF Mass Spectrometer 49
2.3.5 Triple-Quadrupole Mass Spectrometer 49
2.3.6 Triple-Quadrupole TOF Mass Spectrometer 50
2.4 PROTEIN FRACTIONATION 51
2.4.1 Polyacrylamide Gel Electrophoresis 51
2.4.2 Liquid Chromatography 53
2.5 IMPACT OF MS IN CANCER 58
2.5.1 Identification of a Drug Target 58
2.6 CONCLUSIONS 63
REFERENCES 64
3 QUANTITATIVE PROTEOMICS 71
3.1 INTRODUCTION 71
3.2 WHAT IS BEING MEASURED IN QUANTITATIVE PROTEOMICS? 72
3.3 TWO-DIMENSIONAL POLYACRYLAMIDE GEL ELECTROPHORESIS 72
3.4 TWO-DIMENSIONAL DIFFERENCE GEL ELECTROPHORESIS 75
3.5 SOLUTION-BASED QUANTITATIVE METHODS 77
3.5.1 Stable Isotope Labeling 77
3.5.2 Isotope-Coded Affinity Tags 78
3.5.3 Isobaric Tag for Relative and Absolute Quantitation 82
3.5.4 Stable Isotope Labeling of Amino Acids in Culture 82
3.6 NONISOTOPIC SOLUTION-BASED QUANTITATION 87
3.6.1 Subtractive Proteomics—Peptide Counting 87
3.6.2 Subtractive Proteomics—Peak Intensity 91
3.7 CONCLUSIONS 93
REFERENCES 95
4 PROTEOMIC ANALYSIS OF POSTTRANSLATIONAL MODIFICATIONS 99
4.1 INTRODUCTION 99
4.2 PHOSPHORYLATION 102
4.2.1 Identification of Phosphorylated Proteins 106
4.2.2 Phosphopeptide Mapping 107
4.2.3 Collision-Induced Dissociation 107
4.2.4 Electron Capture and Electron Transfer Dissociation 110
4.2.5 Electron Transfer Dissociation 110
4.2.6 Enrichment of Phosphopeptides 111
4.2.7 Immunoaffinity Chromatography 111
4.2.8 Immobilized Metal Affinity Chromatography 112
4.2.9 Metal Oxide Affinity Chromatography 115
4.3 GLYCOSYLATION 115
4.3.1 Mass Spectrometry Characterization 117
4.3.2 Electron Capture and Electron Transfer Dissociation 119
4.3.3 Targeted Identification of Glycoproteins 119
4.3.4 Proteome-Wide Identification of Glycoproteins 120
4.4 OTHER POSTTRANSLATIONAL MODIFICATIONS 121
4.5 CONCLUSIONS 122
REFERENCES 122
5 CHARACTERIZATION OF PROTEIN COMPLEXES 129
5.1 INTRODUCTION 129
5.2 METHODS FOR ISOLATING PROTEIN COMPLEXES 132
5.2.1 Optimizing Protein Complex Isolation 132
5.2.2 Importance of Optimizing Isolation Conditions 134
5.2.3 Oligoprecipitation 136
5.3 PROTEOME SCREENING USING TANDEM AFFINITY PURIFICATION 140
5.4 YEAST TWO-HYBRID SCREENING 143
5.5 QUICK LC–MS METHOD TO IDENTIFY SPECIFICALLY BOUND PROTEINS 145
5.6 PROTEIN ARRAYS 147
5.7 FLUORESCENCE MICROSCOPY 149
5.8 MULTIEPITOPE LIGAND CARTOGRAPHY 151
5.9 CONCLUSIONS 152
REFERENCES 153
6 GLOBAL PHOSPHORYLATION ANALYSIS 157
6.1 INTRODUCTION 157
6.2 GLIOBLASTOMA MULTIFORME 158
6.2.1 Effect of EGFRvIII Expression of Phosphorylation 158
6.2.2 Validation of the Role of c-Met Signaling 160
6.3 APOPTOSIS AND CANCER 162
6.3.1 Global Discovery of Overlapping Kinase and Caspase Targets 163
6.3.2 Functional Relevance of Overlapping CK2 and Caspase 3 Motifs 166
6.4 DASATINIB AND PROTEIN SIGNALING 167
6.4.1 Global Phosphorylation Analysis of Dasatinib-Treated Leukemia Cells 168
6.5 DRIVER AND PASSENGER KINASE MUTATIONS 170
6.5.1 Global Phosphorylation Analysis for the Identification of Driver Kinases 172
6.5.2 Validation of Global Phosphorylation Data 175
6.5.3 Global Phosphotyrosine Analysis of Xenograft Models 177
6.6 CONCLUSIONS 177
REFERENCES 178
7 THE SEARCH FOR BIOMARKERS IN BIOFLUIDS 183
7.1 INTRODUCTION 183
7.2 COLLECTION AND STORAGE OF BIOFLUIDS 185
7.3 COMMONLY USED BIOFLUIDS FOR BIOMARKER DISCOVERY 187
7.3.1 Blood 187
7.3.2 Characterization of the Serum and Plasma Proteome 189
7.4 URINE 194
7.5 CEREBROSPINAL FLUID 197
7.6 SALIVA 199
7.7 OTHER BIOFLUIDS 201
7.8 CONCLUSIONS 201
REFERENCES 202
8 PROTEOMIC PATTERNS: A NEW PARADIGM IN DIAGNOSTICS AND THERAPEUTICS? 207
8.1 INTRODUCTION 207
8.2 MASS SPECTROMETRY AS A CLINICAL TOOL 208
8.3 PROTEOMIC PATTERN TECHNOLOGY 209
8.4 DIAGNOSIS OF OVARIAN CANCER USING PROTEOMIC PATTERNS 212
8.5 PROTEOMIC PATTERNS SKYROCKET 214
8.6 TECHNOLOGY ADVANCES IN PROTEOMIC PATTERNS 216
8.6.1 The Move to Higher Resolution Mass Spectrometers 216
8.6.2 Magnetic Particles and High-Resolution MALDI-TOF 217
8.7 TO IDENTIFY OR NOT IDENTIFY: THAT IS THE QUESTION 219
8.8 CRITICISMS 221
8.9 CONCLUSIONS 223
REFERENCES 224
9 THE EMERGENCE OF PROTEIN ARRAYS 227
9.1 INTRODUCTION 227
9.2 PROTEIN ARRAYS 228
9.3 TYPES OF PROTEIN ARRAYS 229
9.4 TARGET PROTEIN ARRAYS 229
9.5 CAPTURE ARRAYS 232
9.5.1 Binding Molecules 234
9.5.2 Aptamer Arrays 238
9.6 REVERSE-PHASE PROTEIN MICROARRAYS 240
9.6.1 Applications of Reverse-Phase Protein Arrays to Clinical Specimens 241
9.7 TISSUE MICROARRAYS 242
9.7.1 Many Tissues, One Antibody 243
9.7.2 Many Tissues, Many Antibodies 244
9.8 CONCLUSIONS 246
REFERENCES 247
10 THE ROLE OF PROTEOMICS IN PERSONALIZED MEDICINE 253
10.1 INTRODUCTION 253
10.2 THE NEED FOR PROTEOMICS IN PERSONALIZED MEDICINE 256
10.3 PROTEIN PANEL DISCOVERY 257
10.4 GUIDING THE SURGEON THROUGH IMAGING 259
10.5 PERSONALIZED MEDICINE BY SHRINKING THE PROTEOMIC UNIVERSE 263
10.5.1 Targeted Mass Spectrometry 263
10.5.2 Targeted Arrays 268
10.6 INSTRUMENTATION REQUIREMENTS 269
10.7 CONCLUSIONS 271
REFERENCES 271
11 THE CRITICAL ROLE OF BIOINFORMATICS 275
11.1 INTRODUCTION 275
11.2 PROTEIN IDENTIFICATION 276
11.2.1 Protein Databases 276
11.2.2 Peptide Mapping 277
11.2.3 Tandem Mass Spectrometry 278
11.2.4 Peptide Spectral Libraries 281
11.3 PROTEIN QUANTITATION SOFTWARE 281
11.3.1 SDS-PAGE 281
11.3.2 Stable Isotope Labeling 282
11.3.3 Label-Free Quantitation 283
11.3.4 Spectral Counting Quantitation 283
11.4 PROTEIN PATHWAY ANALYSIS 284
11.5 PROTEOME DATA REPOSITORIES 285
11.5.1 Information Storage in MS-Based Proteomics Databases 288
11.6 CONCLUSIONS 288
REFERENCES 289
12 FUTURE PROSPECTS OF PROTEOMICS IN CANCER RESEARCH 293
12.1 INTRODUCTION 293
12.2 SIGNIFICANT DEVELOPMENTS OVER THE PAST DECADE 294
12.3 THE MOVE FROM WESTERN TO MASS SPECTROMETRY 295
12.4 THE FUTURE OF PROTEIN IDENTIFICATION 295
12.4.1 Top-Down Mass Spectrometry 298
12.4.2 Bottom-Up Mass Spectrometry 301
12.4.3 Ionization 301
12.5 GLOBAL QUANTITATIVE PROTEOMICS 303
12.6 THE SHRINKING UNIVERSE OF PROTEOMICS 305
12.7 OMIC DATA INTEGRATION 308
12.8 METABOLOMICS 310
12.9 CONCLUSIONS 311
REFERENCES 312
INDEX 317

<p>Helps researchers in proteomics and oncology work together to understand, prevent, and cure cancer<br></p><p>Proteomic data is increasingly important to understanding the origin and progression of cancer; however, most oncologic researchers who depend on proteomics for their studies do not collect the data themselves. As a result, there is a knowledge gap between scientists, who devise proteomic techniques and collect the data, and the oncologic researchers, who are expected to interpret and apply proteomic data. Bridging the gap between proteomics and oncology research, this book explains how proteomic technology can be used to address some of the most important questions in cancer research.<br></p><p>Proteomic Applications in Cancer Detection and Discovery enables readers to understand how proteomic data is acquired and analyzed and how it is interpreted. Author Timothy Veenstra has filled the book with examples—many based on his own firsthand research experience—that clearly demonstrate the application of proteomic technology in oncology research, including the discovery of novel biomarkers for different types of cancers.<br></p><p>The book begins with a brief introduction to systems biology, explaining why cancer is a systems biology disease. Next, it covers such topics as:<br></p><ul> <li>Mass spectrometry in cancer research </li> <li>Application of proteomics to global phosphorylation analysis </li> <li>Search for biomarkers in biofluids </li> <li>Rise and fall of proteomic patterns for cancer diagnostics </li> <li>Emergence of protein arrays </li> <li>Role of proteomics in personalized medicine </li></ul><p>The final chapter is dedicated to the future prospects of proteomics in cancer research.<br></p><p>By guiding readers through the latest proteomic technologies and their applications in cancer research, Proteomic Applications in Cancer Detection and Discovery enhances the ability of researchers in proteomics and researchers in oncology to collaborate in order to better understand cancer and develop strategies to prevent and treat it.<br></p>

Helps researchers in proteomics and oncology work together to understand, prevent, and cure cancer
Proteomic data is increasingly important to understanding the origin and progression of cancer; however, most oncologic researchers who depend on proteomics for their studies do not collect the data themselves. As a result, there is a knowledge gap between scientists, who devise proteomic techniques and collect the data, and the oncologic researchers, who are expected to interpret and apply proteomic data. Bridging the gap between proteomics and oncology research, this book explains how proteomic technology can be used to address some of the most important questions in cancer research.
Proteomic Applications in Cancer Detection and Discovery enables readers to understand how proteomic data is acquired and analyzed and how it is interpreted. Author Timothy Veenstra has filled the book with examples—many based on his own firsthand research experience—that clearly demonstrate the application of proteomic technology in oncology research, including the discovery of novel biomarkers for different types of cancers.
The book begins with a brief introduction to systems biology, explaining why cancer is a systems biology disease. Next, it covers such topics as:
Mass spectrometry in cancer research Application of proteomics to global phosphorylation analysis Search for biomarkers in biofluids Rise and fall of proteomic patterns for cancer diagnostics Emergence of protein arrays Role of proteomics in personalized medicine The final chapter is dedicated to the future prospects of proteomics in cancer research.
By guiding readers through the latest proteomic technologies and their applications in cancer research, Proteomic Applications in Cancer Detection and Discovery enhances the ability of researchers in proteomics and researchers in oncology to collaborate in order to better understand cancer and develop strategies to prevent and treat it.

Content: Preface x Acknowledgements xii 1 Systems Biology 1 2 Mass Spectrometry in Cancer Research 44 3 Quantitative Proteomics 93 4 Proteome Analysis of Post-translational Modifications 145 5 Characterization of Protein Complexes 196 6 Global Phosphorylation Analysis 242 7 The Search for Biomarkers in Biofluids 281 8 Proteomic Patterns: A New Paradigm in Diagnostics and Therapeutics? 309 9 The Emergence of Protein Arrays 370 10 The Role of Proteomics in Personalized Medicine 413 11 The Critical Role of Bioinformatics 449 12 Future Prospects of Proteomics in Cancer Research 480 Index 516
Abstract: Bridging the knowledge gap between scientists that develop and apply proteomics technologies and oncologists who focus on understanding the biological basis behind cancer manifestation and progression, this title provides an account of how the multiple facets of proteomics have been applied to cancer. Read more...

"Bridging the knowledge gap between scientists that develop and apply proteomics technologies and oncologists who focus on understanding the biological basis behind cancer manifestation and progression, Proteomic Applications in Cancer Detection and Discovery provides an up-to-date account of how the multiple facets of proteomics have been applied to cancer. By balancing the treatment of technologies and applications, the book enables analytical scientists and oncologists, post-doctoral researchers, major research or medical centers, cancer researchers, pharmaceutical researchers, chemists, and biologists to better understand both"-- Résumé de l'éditeur

2014-06-12