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3-D cell-based biosensors in drug discovery programs : microtissue engineering for high throughput screening / by William S. Kisaalita. — Boca Raton, Fla. : CRC ; London : Taylor & Francis [distributor], 2010. – (63.3034/K61)

Contents

    Contents
    
    Preface xv
    Author xvii
    PART I Introduction
    Chapter 1 Biosensors and Bioassays 3
    1.1 Conventional Biosensors 3
    1.2 Conventional Biosensor Applications 8
    1.3 Cell-Based Biosensors versus Cell-Based Assays (Bioassays) 13
    1.4 3D Cultures 15
    1.5 Concluding Remarks 19
    References 19
    Chapter 2 Target-Driven Drug Discovery 23
    2.1 Drug Discovery and Development 23
    2.2 The Taxol (Paclitaxel) Discovery Case 25
    2.3 The Gleevec (Imatinib Mesylate) Discovery Case 35
    2.4 Target-Driven Drug Discovery Paradigm 43
    2.5 The New Discovery Paradigm Promise 47
    2.6 Concluding Remarks 49
    References 51
    PART II 3D versus 2D Cultures
    Chapter 3 Comparative Transcriptional Profiling and Proteomics 57
    3.1 Transcriptional Profiling Studies 57
    3.2 Comparative GO Annotation Analysis 60
    3.3 Proteomics Studies 65
    3.4 Concluding Remarks 67
    References 74
    Chapter 4 Comparative Structure and Function 77
    4.1 Complex Physiological Relevance
    4.2 Cardiomyocyte Contractility
    4.3 Liver Cell Bile Canaliculi In Vitro 82
    4.4 Nerve Cell Voltage-Gated Calcium Signaling 84
    4.5 Concluding Remarks 89
    References 90
    PART III Emerging Design Principles
    Chapter 5 Chemical Microenvironmental Factors 97
    5.1 Cell Adhesion Molecules 97
    5.2 Short-Range Chemistry
    5.3 Long-Range Chemistry
    5.4 Concluding Remarks
    References
    Chapter 6 Spatial and Temporal Microenvironmental Factors 121
    6.1 Nano-and Microstructured Surfaces 122
    6.2 Scaffolds 122
    6.3 Nano and Scaffold-Combined Structures 148
    6.4 Temporal Factor 148
    6.5 Concluding Remarks 153
    References 160
    Chapter 7 Material Physical Property and Force Microenvironmental Factors 169
    7.1 Basics 169
    7.2 Stiffness-Dependent Responses 180
    7.3 Force-Dependent Responses 189
    7.4 Concluding Remarks 193
    References 198
    Chapter 8 Proteomics as a Promising Tool in the Search for 3D Biomarkers 207
    8.1 Why Search for Three-Dimensionality Biomarkers? 207
    8.2 Cellular Adhesions 209
    8.3 Signaling Pathways 212
    8.4 Overview of Proteomics Techniques 213
    8.5 Study Design and Methods 215
    8.6 Concluding Remarks 217
    References 217
    Chapter 9 Readout Present and Near Future 221
    9.1 Readout Present and Near Future 221
    9.2 Fluorescence-Based Readouts 224
    9.3 Bioluminescence-Based Readouts 230
    9.4 Label-Free Biosensor Readouts 235
    9.5 Concluding Remarks 245
    References 246
    Chapter 10 Ready-to-Use Commercial 3D Plates 253
    10.1 Introduction 253
    10.2 Algimatrix 254
    10.3 Extracel 257
    10.4 Ultra-Web 259
    10.5 Market Opportunities 262
    10.6 Concluding Remarks 264
    References 265
    PART IV Technology Deployment Challenges and Opportunities
    Chapter 11 Challenges to Adopting 3D Cultures in HTS Programs 269
    11.1 Typical HTS Laboratory and Assay Configurations 269
    11.2 Just-in-Time Reagents Provision Model 274
    11.3 Limited Value-Addition from 3D Culture Physiological Relevance: Transepithelium Drug Transport and Induction of Drug Metabolizing Enzyme Cases 276
    11.4 Paucity of Conclusive Support of 3D Culture Superiority 283
    References 285
    Chapter 12 Cases for 3D Cultures in Drug Discovery 289
    12.1 Three Cases
    12.2 The β1-Integrin Monoclonal Antibody Case
    12.3 The Matrix Metalloproteinase Inhibitors Case
    12.4 Resistance to the Chemotherapeutic Agents Case 297
    12.5 Concluding Remarks 300
    References 301
    Chapter 13 Ideal Case Study Design 307
    13.1 Rationale for the Case Study 307
    13.2 Why Hepatotoxicity? 308
    13.3 Hepatotoxicity and hESC-Derived Hepatocyte-Like Cells 310
    13.4 Study Design and Methods 317
    13.5 Analysis and Expected Results 319
    References 320
    Appendix A Patents for 3D Scaffolds 323
    References 328
    Appendix B Current Drug Targets 331
    Appendix C Popular Cell Lines in Drug Discovery 357
    C1 HEK 293 357
    C1.1 Background 357
    C1.2 Morphology and Ploidy 358
    C2 CHO 358
    C2.1 Background 358
    C2.2 Morphology and Ploidy 358
    C3 HeLa 358
    C3.1 Background 358
    C3.2 Morphology and Ploidy 359
    C4 HepG2 359
    C4.1 Background 359
    C4.2 Morphology and Ploidy 360
    C5 U2OS 360
    C5.1 Background 360
    C5.2 Morphology and Ploidy 360
    C6 COS-7/CV-1 360
    C6.1 Background 360
    C6.2 Morphology and Ploidy 361
    References 361
    Appendix D Stem Cells in Drug Discovery 363
    References 368
    Index 373
    Company Index 385