Textbook of Personalized Medicine (eBook)
XXVI, 430 Seiten
Springer New York (Verlag)
978-1-4419-0769-1 (ISBN)
Personalized medicine, which simply means selection of treatment best suited for an individual, involves integration and translation of several new technologies in clinical care of patients. The scope is much broader than indicated by the term genomic medicine because many non-genomic factors are taken into consideration in developing personalized medicine. Basic technologies for personalized medicine, of which molecular diagnostics has the biggest share, are mentioned briefly and appropriate references are given for further information. Commercial aspects are discussed briefly in a chapter and detailed analysis of markets and companies involved in personalized medicine is presented in a special report on this topic.
There is increasing interest in personalized medicine. Considerable advances have taken place in molecular biology and biotechnology to make personalized medicine a viable option, but some misconceptions still exist, both in the academic and commercial sectors. There is lack of a suitable source of information that provides both the fundamentals as well as applications of personalized medicine. As the latest version of the first monograph on personalized medicine published in 1998, this volume, Textbook of Personalized Medicine, summarizes the author's efforts during the past decade, as well as reviews selected studies done during this period in a readable format for the physicians and scientists. It is hoped that physicians, pharmacists, scientists and interested lay readers with basic scientific knowledge will find this book useful.
Professor K. K. Jain is trained in neurosurgery with specialist qualifications. He worked for 25 years in various academic positions and private practice worldwide mostly in Canada and the US. His clinical research interests during these years were use of lasers for microneurosurgery and hyperbaric oxygen. He has been involved in biotechnology since 1989, when he moved to Basel, Switzerland. He was elected a fellow of the Faculty of Pharmaceutical Medicine of the Royal Colleges of UK in 2000. He is the author of over 405 publications including 15 books and 48 special reports. Important books are Textbook of Gene Therapy, Textbook of Hyperbaric Medicine and Handbook of Nanomedicine. He is a member of editorial board of several journals and senior associate editor of MedLink Neurology (San Diego, California), a continuing education program for neurologists. Prof. Jain has been interested in integrating various biotechnologies to develop personalized medicine since 1997. He wrote the first report on personalized medicine, which was published in 1998 by Decision Resources Inc. The report titled Personalized Medicine: scientific and commercial aspects is continuously updated and published at Jain PharmaBiotech, Basel. He lectures and conducts workshops worldwide.
Personalized medicine, which simply means selection of treatment best suited for an individual, involves integration and translation of several new technologies in clinical care of patients. The scope is much broader than indicated by the term genomic medicine because many non-genomic factors are taken into consideration in developing personalized medicine. Basic technologies for personalized medicine, of which molecular diagnostics has the biggest share, are mentioned briefly and appropriate references are given for further information. Commercial aspects are discussed briefly in a chapter and detailed analysis of markets and companies involved in personalized medicine is presented in a special report on this topic.There is increasing interest in personalized medicine. Considerable advances have taken place in molecular biology and biotechnology to make personalized medicine a viable option, but some misconceptions still exist, both in the academic and commercial sectors. There is lack of a suitable source of information that provides both the fundamentals as well as applications of personalized medicine. As the latest version of the first monograph on personalized medicine published in 1998, this volume, Textbook of Personalized Medicine, summarizes the author's efforts during the past decade, as well as reviews selected studies done during this period in a readable format for the physicians and scientists. It is hoped that physicians, pharmacists, scientists and interested lay readers with basic scientific knowledge will find this book useful.
Professor K. K. Jain is trained in neurosurgery with specialist qualifications. He worked for 25 years in various academic positions and private practice worldwide mostly in Canada and the US. His clinical research interests during these years were use of lasers for microneurosurgery and hyperbaric oxygen. He has been involved in biotechnology since 1989, when he moved to Basel, Switzerland. He was elected a fellow of the Faculty of Pharmaceutical Medicine of the Royal Colleges of UK in 2000. He is the author of over 405 publications including 15 books and 48 special reports. Important books are Textbook of Gene Therapy, Textbook of Hyperbaric Medicine and Handbook of Nanomedicine. He is a member of editorial board of several journals and senior associate editor of MedLink Neurology (San Diego, California), a continuing education program for neurologists. Prof. Jain has been interested in integrating various biotechnologies to develop personalized medicine since 1997. He wrote the first report on personalized medicine, which was published in 1998 by Decision Resources Inc. The report titled Personalized Medicine: scientific and commercial aspects is continuously updated and published at Jain PharmaBiotech, Basel. He lectures and conducts workshops worldwide.
FM1.pdf 1
1.pdf 24
Chapter 1 24
Basics of Personalized Medicine 24
Definition of Personalized Medicine 24
History of Medical Concepts Relevant to Personalized Medicine 26
Molecular Biological Basis of Personalized Medicine 28
The Human Genome 29
Chromosomes 29
Genes 30
The Genetic Code 30
Gene Expression 31
DNA Sequences and Structure 31
Single Nucleotide Polymorphisms 32
Genotype and Haplotypes 32
Genetic Variations in the Human Genome 32
Insertions and Deletions in the Human Genome 33
Large Scale Variation in Human Genome 34
Variation in Copy Number in the Human Genome 34
Structural Variants in the Human Genome 35
Mapping and Sequencing of Structural Variants from Human Genomes 36
1,000 Genomes Project 37
Human Variome Project 38
Basics Technologies for Developing Personalized Medicine 38
Definitions of Technologies Relevant to Personalized Medicine 38
Problems with the ICH Definitions of Pharmacogenomics and Pharmacogenetics 39
Relationship of Various Technologies to Personalized Medicine 39
Conventional Medicine vs. Personalized Medicine 40
Genetic Basis of Personalized Medicine 41
Genetic Medicine 41
Human Disease and Genes 41
Genetic and Environmental Interactions in Etiology of Human Diseases 42
Mass Analysis of DNA from Whole Populations 42
Role of Genetics in Development of Personalized Medicines 43
Genetic Databases 43
Genetic Epidemiology 44
Limitations of Medical Genetics and Future Prospects 45
Genetics vs. Epigenetics 45
Role of Systems Biology in Personalized Medicine 45
Systems Pharmacology 47
Systems Medicine 47
A Personalized Approach to Environmental Factors in Disease 48
Reclassification of Diseases 49
Summary 50
2.pdf 51
Chapter 2 51
Molecular Diagnostics as Basis of Personalized Medicine 51
Introduction 51
Molecular Diagnostic Technologies 51
DNA Sequencing 52
Biochips and Microarrays 52
DNA Biochip Technology for Developing Personalized Medicine 52
Role of Protein Biochips in Personalized Medicine 56
Cytogenetics 57
Molecular Cytogenetics as Basis for Personalized Medicine 57
Cytomics as a Basis for Personalized Medicine 58
SNP Genotyping 59
Technologies for SNP Analysis 59
Applications of SNPs Relevant to Personalized Medicine 59
Concluding Remarks on SNP Genotyping 61
Haplotyping 62
HapMap Project 63
Predicting Drug Response with HapMap 64
Nanodiagnostics for Personalized Medicine 64
Cantilevers for Personalized Medical Diagnostics 65
Nanopore-Based Technology for Single Molecule Identification 66
Application of Proteomics in Molecular Diagnosis 66
Comparison of Proteomic and Genomic Approaches in Personalized Medicine 66
Gene Expression Profiling 67
DNA Microarrays for Gene Expression Studies 68
Analysis of Single-Cell Gene Expression 69
Gene Expression Profiling Based on Alternative RNA Splicing 69
Molecular Imaging and Personalized Medicine 70
Monitoring In Vivo Gene Expression by Molecular Imaging 71
Glycomics-Based Diagnostics 71
Combination of Diagnostics and Therapeutics 72
Point-of-Care Diagnosis 72
Point-of-Care Diagnosis of Infections 74
Advantages vs. Disadvantages of Point-of-Care Diagnosis 74
Future Prospects of Point-of-Care Diagnosis 75
Genetic Testing for Disease Predisposition 75
Personal Genetic Service 76
Role of Diagnostics in Integrated Healthcare 76
Concept of Integrated Healthcare 76
Components of Integrated Healthcare 77
Screening 77
Disease Prediction 77
Early Diagnosis 77
Prevention 78
Therapy Based on Molecular Diagnosis 78
Monitoring of Therapy 78
Advantages and Limitations of Integrated Healthcare 78
Future of Molecular Diagnostics in Personalized Medicine 79
Summary 79
3.pdf 81
Chapter 3 81
Role of Biomarkers in Personalized Medicine 81
Introduction 81
Technologies for Discovery of Biomarkers 82
Systems Biology Approach to Biomarker Identification 82
Epigenomic Technologies 82
Discovery of Methylation Biomarkers 84
Proteomic Strategies for Biomarker Identification 84
Proteomic Technologies for Detection of Biomarkers in Body Fluids 85
Biomarkers for Diagnostics 85
Biomarkers for Drug Development 86
Use of Biomarkers for Developing MAb Therapy in Oncology 86
Biobanking, Biomarkers and Personalized Medicine 87
Expression Signatures as Diagnostic/Prognostic Tools 88
Biomarkers for Monitoring Response to Therapy 88
Drug Rescue by Biomarker-Based Personalized Medicine 89
Future Role of Biomarkers in Personalized Medicine 90
Summary 90
4.pdf 91
Chapter 4 91
Pharmacogenetics 91
Basics of Pharmacogenetics 91
Role of Molecular Diagnostics in Pharmacogenetics 92
Role of Pharmacogenetics in Pharmaceutical Industry 93
Study of the Drug Metabolism and Pharmacological Effects 93
Causes of Variations in Drug Metabolism 94
Enzymes Relevant to Drug Metabolism 94
Pharmacogenetics of Phase I Metabolism 95
Cyp450 95
P450 CYP 2D6 Inhibition by Selective Serotonin Reuptake Inhibitors (SSRIs) 97
Cytochrome P450 Polymorphisms and Response to Clopidogrel 98
Lansoprazole and Cytochrome P450 98
Glucose-6-Phosphate Dehydrogenase 99
Pharmacogenetics of Phase II Metabolism 100
N-Acetyltransferase 100
Uridine Diphosphate-Glucuronosyltransferase 101
Measurement of CYP Isoforms 101
Polymorphism of Drug Transporters 102
Genetic Variation in Drug Targets 103
Polymorphisms of Kinase Genes 104
Effect of Genetic Polymorphisms on Response of Disease to Drugs 104
Ethnic Differences in Drug Metabolism 105
Gender Differences in Pharmacogenetics 105
Role of Pharmacogenetics in Drug Safety 106
Adverse Drug Reactions 106
ADRs in Children 106
Genetically Determined ADRs 107
ADRs of Chemotherapy 108
Malignant Hyperthermia 109
Pharmacogenetics of Clozapine-Induced Agranulocytosis 109
Role of Pharmacogenetics in Warfarin Therapy 110
Role of Pharmacogenetics in Carbamazepine Therapy 111
Role of Pharmacogenetics in Statin Therapy 111
FDA Consortium for Genetic Biomarkers of Serious Adverse Events 112
Therapeutic Drug Monitoring, Phenotyping, and Genotyping 113
Therapeutic Drug Monitoring 113
Phenotyping 113
Genotyping 115
Genotyping vs. Phenotyping 115
Phenomics 116
Limitations of Genotype-Phenotype Association Studies 117
Molecular Toxicology in Relation to Personalized Medicines 117
Toxicogenomics 117
Gene Expression Studies 118
Genomics and the Prediction of Xenobiotic Toxicity 119
Pharmacogenetics in Clinical Trials 119
Clinical Implications of Pharmacogenetics 120
Application of CYP450 Genotyping in Clinical Practice 120
Genotype-Based Drug Dose Adjustment 120
Examples of use of Pharmacogenetics in Clinical Pharmacology 121
Linking Pharmacogenetics with Pharmacovigilance 122
Genetic Susceptibility to ADRs 122
Linking Genetic Testing to Postmarketing ADR Surveillance 122
Recommendations for the Clinical Use of Pharmacogenetics 123
Limitations of Pharmacogenetics 123
Future Role of Pharmacogenetics in Personalized Medicine 124
Summary 124
5.pdf 126
Chapter 5 126
Pharmacogenomics 126
Introduction 126
Basics of Pharmacogenomics 126
Pharmacogenomics and Drug Discovery 128
Preclinical Prediction of Drug Efficacy 129
Pharmacogenomics and Clinical Trials 130
Impact of Genetic Profiling on Clinical Studies 130
Limitations of the Pharmacogenomic-Based Clinical Trials 132
Pharmacogenomic Aspects of Major Therapeutic Areas 133
Oncogenomics 133
Oncogenes 133
Tumor Suppressor Genes 134
Cardiogenomics 134
Neurogenomics 138
Pharmacogenomics of AD 138
Pharmacogenomics of Depression 139
Pharmacogenomics of Schizophrenia 139
Summary 140
6.pdf 141
Chapter 6 141
Role of Pharmacoproteomics 141
Basics of Proteomics 141
Proteomic Approaches to the Study of Pathophysiology of Diseases 142
Single Cell Proteomics for Personalized Medicine 142
Diseases Due to Misfolding of Proteins 143
Therapies for Protein Misfolding 143
Significance of Mitochondrial Proteome in Human Disease 144
Proteomic Technologies for Drug Discovery and Development 145
Role of Reverse-Phase Protein Microarray in Drug Discovery 145
Role of Proteomics in Clinical Drug Safety 145
Toxicoproteomics 146
Application of Pharmacoproteomics in Personalized Medicine 148
Summary 148
7.pdf 149
Chapter 7 149
Role of Metabolomics in Personalized Medicine 149
Metabolomics and Metabonomics 149
Metabolomics Bridges the Gap Between Genotype and Phenotype 150
Metabolomics, Biomarkers and Personalized Medicine 151
Metabolomic Technologies 151
Urinary Profiling by Capillary Electrophoresis 152
Lipid Profiling 153
Role of Metabolomics in Biomarker Identification and Pattern Recognition 153
Validation of Biomarkers in Large-Scale Human Metabolomics Studies 154
Pharmacometabonomics 154
Metabonomic Technologies for Toxicology Studies 155
Metabonomics/Metabolomics and Personalized Nutrition 156
Summary 156
8.pdf 157
Chapter 8 157
Personalized Biological Therapies 157
Introduction 157
Recombinant Human Proteins 157
Therapeutic Monoclonal Antibodies 158
Cell Therapy 158
Autologous Tissue and Cell Transplants 159
Stem Cells 159
Role of Stem Cells Derived from Unfertilized Embryos 159
Cloning and Personalized Cell Therapy 160
Use of Stem Cells for Drug Testing 160
Gene Therapy 160
Personalized Vaccines 161
Personalized Vaccines for Viral Diseases 161
Personalized Cancer Vaccines 162
Patient-Specific Cancer Vaccines 162
Antigen-Specific Vaccines 163
Autologous Cell Vaccines 163
Personalized Melanoma Vaccines 165
Antisense Therapy 165
RNA Interference 166
MicroRNAs 166
Summary 167
9.pdf 168
Chapter 9 168
Development of Personalized Medicine 168
Introduction 168
Non-genomic Factors in the Development of Personalized Medicine 169
Personalized Medicine Based on Circadian Rhythms 169
Intestinal Microflora 170
Gut Microbiome Compared to Human Genome 170
Metabolic Interactions of the Host and the Intestinal Microflora 171
Role of Drug Delivery in Personalized Medicine 171
Role of Molecular Imaging in Personalized Medicine 172
Personalized Approach to Clinical Trials 172
Use of Bayesian Approach in Clinical Trials 172
Individualizing Risks and Benefits in Clinical Trials 173
Clinical Trials of Therapeutics and Companion Diagnostics 174
Role of Genetic Banking Systems and Databases 174
Role of Biobanks in the Development of Personalized Medicine 174
UK Biobank 175
Biobanking and Development of Personalized Medicine in the EU 175
CARTaGENE for Biobanks in Canada 176
Personalized Medicine Based on PhysioGenomics™ Technology 177
Role of Bioinformatics in Development of Personalized Medicine 178
Health Information Management 179
Electronic Health Records 179
Linking Patient Medical Records and Genetic Information 180
Management of Personal Genomic Data 181
Personalized Prognosis of Disease 181
Integration of Technologies for Development of Personalized Medicine 182
Summary 182
10.pdf 183
Chapter 10 183
Personalized Therapy for Cancer 183
Introduction 183
Challenges of Cancer Classification 183
Relationships of Technologies for Personalized Management of Cancer 184
Impact of Molecular Diagnostics on the Management of Cancer 185
Analysis of RNA Splicing Events in Cancer 185
Analysis of Chromosomal Alterations in Cancer Cells 186
Cancer Classification Using Microarrays 186
Detection of Loss of Heterozygosity (LOH) 187
Diagnosis of Cancer of an Unknown Primary 188
Diagnostics for Detection of Minimal Residual Disease (MRD) 188
Fluorescent In Situ Hybridization 189
Gene Expression Profiling 189
Gene Expression Profiles Predict Chromosomal Instability in Tumors 190
Isolation and Characterization of Circulating Tumor Cells (CTCs) 191
Modulation of CYP450 Activity for Cancer Therapy 191
Personalized Therapies Based on Oncogenic Pathway Signatures 192
Role of Molecular Imaging in Personalized Therapy of Cancer 193
Molecular Imaging for Personalized Drug Development in Oncology 193
Molecular Imaging as Guide to Cancer Treatment 194
Functional Diffusion MRI 195
Role of FDG-PET/CT in Personalizing Cancer Treatment 196
Tumor Imaging and Elimination by Targeted Gallium Corrole 197
Unraveling the Genetic Code of Cancer 197
Cancer Prognosis 198
Detection of Mutations for Risk Assessment and Prevention 199
Impact of Biomarkers on Management of Cancer 199
Predictive Biomarkers for Cancer 199
HER-2/neu Oncogene as a Biomarker for Cancer 200
l-asparaginase (l-ASP)Treatment of Cancer Guided by a Biomarker 200
Determination of Response to Therapy 201
Phenotype-Based Cell Culture Assays 201
Ex Vivo Testing of Tumor Biopsy for Chemotherapy Sensitivity 201
Genomic Approaches to Predict Response to Anticancer Agents 202
Gene Expression Patterns to Predict Response of Cancer to Therapy 202
Genomic Analysis of Tumor Biopsies 202
Mutation Detection at Molecular Level 203
Role of Genetic Variations in Susceptibility to Anticancer Drugs 203
Proteomic Analysis of Tumor Biopsies to Predict Response to Treatment 203
Real-time Apoptosis Monitoring 204
Serum Nucleosomes as Indicators of Sensitivity to Chemotherapy 204
Targeted Microbubbles to Tumors for Monitoring Anticancer Therapy 205
Tissue Systems Biology Approach to Personalized Management of Cancer 206
Targeted Cancer Therapies 206
Targeting Glycoproteins on Cell Surface 206
Targeting Pathways in Cancer 207
Functional Antibody-Based Personalized Therapies 207
Personalized Radiation Therapy 208
Molecular Diagnostics Combined with Cancer Therapeutics 209
Aptamers for Combined Diagnosis and Therapeutics of Cancer 210
Role of Nanobiotechnology in Personalized Management of Cancer 210
Design of Future Cancer Therapies 211
Screening for Personalized Anticancer Drugs 212
Role of Epigenetics in Development of Personalized Cancer Therapies 212
Personalized Therapy of Cancer Based on Cancer Stem Cells 213
Role of Oncoproteomics in Personalized Therapy of Cancer 213
Cancer Tissue Proteomics 214
Pharmacogenomic-Based Chemotherapy 215
Whole Genome Technology to Predict Drug Resistance 215
Anticancer Drug Selection Based on Molecular Characteristics of Tumor 215
Testing Microsatellite-Instability for Response to Chemotherapy 216
Pharmacogenetics of Cancer Chemotherapy 217
CYP1A2 217
Thiopurine Methyltransferase 218
Dihydropyrimidine Dehydrogenase 219
UGT1A1 Test as Guide to Irinotecan Therapy 219
Role of Computational Models in Personalized Anticancer Therapy 220
A Computational Model of Kinetically Tailored Treatment 220
Mathematical Modeling of Tumor Microenvironments 220
Molecular Profiling of Cancer 221
Drug Resistance in Cancer 222
Detection of Drug Resistance in Cancer by Metabolic Profiling 223
Determination of Chemotherapy Response by Topoisomerase Levels 223
A Systems Biology Approach to Drug Resistance in CRC 224
Management of Drug Resistance in Leukemia 224
Overexpression of Multidrug Resistance Gene 225
P53 Mutations 225
A Chemogenomic Approach to Drug Resistance 226
Examples of Personalized Management of Cancer 226
Personalized Management of Breast Cancer 226
Genetic Testing in Breast Cancer as a Guide to Treatment 227
Pharmacogenetics of Breast Cancer 228
Molecular Diagnostics in Breast Cancer 228
Racial Factors in the Management of Breast Cancer 230
Proteomics-Based Personalized Management of Breast Cancer 230
Tests for Prognosis of Breast Cancer 231
Developing Personalized Drugs for Breast Cancer 233
Developing Personalized Drugs for Triple-Negative Breast Cancer 234
Predicting Response to Chemotherapy in Breast Cancer 234
Prediction of Resistance to Therapy in Breast Cancer 237
Prediction of Adverse Reaction to RT in Breast Cancer 238
Prediction of Recurrence in Breast Cancer for Personalizing Therapy 238
TAILORx (Trial Assigning Individualized Options for Treatment) 240
Gene Expression Plus Conventional Predictors of Breast Cancer 241
Future Development of Gene Expression Microarrays for Breast Cancer 242
Personalized Management of Ovarian Cancer 242
Personalized Management of Hematological Malignancies 245
Personalized Management of Acute Leukemias 245
Personalized Management of Chronic Lymphocytic Leukemia 247
Personalized Management of Multiple Myeloma (MM) 247
Personalized Management B Cell Lymphomas 249
Personalized Vaccine for Follicular Lymphoma 249
Personalized Management of Myelodysplasia 250
Personalized Management of Malignant Melanoma 250
Personalized Management of Gastrointestinal Cancer 250
Personalized Management of Esophageal Cancer 250
Personalized Management of CRC 251
Personalized Management of Lung Cancer 254
Determination of Outcome of EGFR Tyrosine Kinase Inhibitor Treatment 254
Testing for Response to Chemotherapy in Lung Cancer 257
Testing for Prognosis of NSCLC 257
Testing for Recurrence of Lung Cancer 258
Role of a New Classification System in the Management of Lung Cancer 258
Personlized Management of Prostate Cancer 259
Benefit of Lifestyle Changes Shown by Gene Expression Studies 259
Personalized Management of Brain Cancer 260
Genetics and Genomics of Brain Cancer 260
Molecular Diagnostics for Personalized Management of Brain Cancer 262
Personalized Chemotherapy of Brain Tumors 264
Biosimulation Approach to Personalizing Treatment of Brain Cancer 265
Personalized Therapy of Oligodendroglial Tumors 266
Personalized Therapy of Neuroblastomas 267
Personalized Management of Germ Cell Brain Tumors 268
Future of Cancer Therapy 268
Challenges for Developing Personalized Cancer Therapies 268
The Cancer Genome Atlas 269
Role of the International Cancer Genome Consortium 269
Using Computer and Imaging Technologies to Personalize Cancer Treatment 271
Integrated Genome-Wide Analysis of Cancer for Personalized Therapy 271
Summary 272
11.pdf 273
Chapter 11 273
Personalized Management of Neurological Disorders 273
Introduction 273
Personalized Drug Development for Neurological Disorders 273
Personalized Drug Discovery 273
Molecular Imaging and CNS Drug Development 273
Personalized Management of AD 275
Personalized Management of PD 276
Discovery of Subgroup-Selective Drug Targets in PD 277
Personalized Management of Epilepsy 277
Choice of the Right AED 278
Pharmacogenetics of Epilepsy 278
Pharmacogenomics of Epilepsy 279
Drug Resistance in Epilepsy 280
Future Prospects for Epilepsy 281
Personalized Management of Migraine 282
Personalized Treatment of MS 282
MBP8298 283
Pharmacogenomics of IFN-b Therapy in MS 284
Future Prospects of Personalized Therapy of MS 285
Personalized Management of Psychiatric Disorders 285
Psychopharmacogenetics 285
COMT Genotype and Response to Amphetamine 286
Genotype and Response to Methylphenidate in Children with ADHD 286
Personalized Antipsychotic Therapy 287
Personalized Antidepressant Therapy 290
Pretreatment EEG to Predict Adverse Effects to Antidepressants 291
Individualization of SSRI Treatment 291
Vilazodone with a Test for Personalized Treatment of Depression 293
Summary 293
12.pdf 294
Chapter 12 294
Personalized Therapy of Cardiovascular Diseases 294
Introduction 294
Role of Cardiovascular Diagnostics in Personalized Management 294
Testing in Coronary Heart Disease 294
SNP Genotyping in Cardiovascular Disorders 295
Cardiovascular Disorders with a Genetic Component 296
Gene Variant as a Risk Factor for Sudden Cardiac Death 298
SNP Chip for Study of Cardiovascular Diseases 299
Pharmacogenomics of Cardiovascular Disorders 299
Modifying the Genetic Risk for MI 300
Management of Heart Failure 300
b-Blockers 300
Bucindolol 301
BiDil 301
Management of Hypertension 302
Pharmacogenomics of Diuretic Drugs 303
Pharmacogenomics of ACE Inhibitors 304
Management of Hypertension by Personalized Approach 304
Pharmacogenetics of Lipid-Lowering Therapies 305
Polymorphisms in Genes Involved in Cholesterol Metabolism 305
Role of eNOS Gene Polymorphisms 306
The STRENGTH Study 307
Personalized Management of Women with Hyperlipidemia 308
Thrombotic Disorders 308
Factor V Leiden Mutation 308
Anticoagulant Therapy 309
Nanotechnology-Based Personalized Therapy of Cardiovascular Diseases 310
Project euHeart for Personalized Management of Cardiovascular Diseases 311
Concluding Remarks 311
Summary 312
13.pdf 313
Chapter 13 313
Personalized Management of Miscellaneous Disorders 313
Management of Viral Infections 313
Management of HIV 313
Genetics of Human Susceptibility to HIV Infection 313
Pharmacogenomics of Antiretroviral Agents 314
Role of Diagnostic Testing in HIV 315
CD4 Counts as a Guide to Drug Therapy for AIDS 315
Drug-Resistance in HIV 315
Measurement of Replication Capacity 316
Prevention of Adverse Reactions to Antiviral Drugs 316
Role of Genetic Variations in Susceptibility to HIV-1 317
Pharmacogenetics and HIV Drug Safety 318
Treatment of Hepatitis B 318
Treatment of Hepatitis C 318
Personalized Management of Tuberculosis (TB) 320
Personalized Management of Skin Disorders 321
Personalized Therapy of Rheumatoid Arthritis (RA) 321
DIATSTATTM Anti-Cyclic Citrullinated Peptides in RA 323
Personalization of COX-2 Inhibitor Therapy 323
Personalization of Infliximab Therapy 324
Personalized Therapy of Asthma 324
Genetic Polymorphism and Response to b2-Adrenergic Agonists 324
Genotyping in Asthma 325
Personalized Approaches in Immunology 326
Pharmacogenetics and Pharmacogenomics of Immunosuppressive Agents 327
Personalized Immunosuppressant Therapy in Organ Transplants 327
Personalized Management of Pain 328
Pharmacogenetics/Pharmacogenomics of Pain 329
Mechanism-Specific Management of Pain 330
Preoperative Testing to Tailor Postoperative Analgesic Requirements 330
Personalized Analgesics 331
Management of Genetic Disorders 332
Personalized Treatment of Cystic Fibrosis 332
Personalized Management of Gastrointestinal Disorders 333
Personalized Therapy of Inflammatory Bowel Disease 333
Personalized Management of Lactose Intolerance 334
Personalized Approach to Addiction 334
Genetic Polymorphism and Management of Alcoholism 334
Personalized Therapy for Smoking Cessation 335
Antidepressant Therapy for Smoking Cessation 335
Effectiveness of Nicotine Patches in Relation to Genotype 335
Personalized Approach to Drug Addiction 336
Personalized Approaches to Miscellaneous Problems 336
Hormone Replacement Therapy in Women 336
Personalized Treatment of Malaria 337
Personalized Management of Renal Disease 338
Personalization of Organ Transplantation 338
Personalization of Kidney Transplantation 339
Personalization of Cardiac Transplantation 339
Prediction of Rejection to Tailor Anti-Rejection Medications 340
Role of Immunological Biomarkers in Monitoring Grafted Patients 341
Improved Matching of Blood Transfusion 341
Personalized Care of Trauma Patients 342
Personalized Anticoagulation 342
Personalized Hyperbaric Oxygen Therapy 343
Summary 344
14.pdf 345
Chapter 14 345
Personalized Preventive Medicine 345
Introduction 345
Personalized Nutrition 346
Nutrigenomics 346
Nutrigenomics and Functional Foods 347
Nutrigenomics and Personalized Medicine 348
Nutrition and Proteomics 348
Personalized Diet Prescription 349
Summary 349
15.pdf 350
Chapter 15 350
Organization of Personalized Medicine 350
Players in the Development of Personalized Medicine 350
Personalized Medicine Coalition 350
Role of Pharmaceutical Industry 351
Production and Distribution of Personalized Medicines 353
Role of Biotechnology Companies 354
Role of life Sciences Industries 354
Collaboration Between the Industry and the Academia 355
Role of the Clinical Laboratories 355
Role of the US Government 356
Role of US Government Institutions in Development of Personalized Medicine 357
NIH’s Roadmap Initiative for Medical Research 357
NIH and Personalized Medicine 358
National Institute of General Medical Sciences 358
National Institute of Standards and Technology 359
Role of Academic Institutions in the USA 360
Clinical Proteomics Program 360
Coriell Personalized Medicine Collaborative™ 360
Delaware Valley Personalized Medicine Project 361
Evaluation of Genetic Tests and Genomic Applications 362
Genomic-Based Prospective Medicine Project 362
Personalized oncology at Massachusetts General Hospital 363
Pharmacogenetics Research Network and Knowledge Base 364
Quebec Center of Excellence in Personalized Medicine 364
Southeast Nebraska Cancer Center’s Personalized Medicine Network 365
Wisconsin Genomics Initiative 365
Role of Healthcare Organizations and Hospitals 365
Signature Genetics 366
The Mayo Clinic Genetic Database 366
Research Center for Personalized Medicine at Mt. Sinai Medical Center 367
Role of the Medical Profession 367
Education of the Physicians 367
Off-Label Prescribing and Personalized Medicine 368
Medical Education 368
Education of the Public 369
Role of the Internet in Development of Personalized Medicine 369
Public Attitude Towards Personalized Medicine 370
Global Scope of Personalized Medicine 371
Personalized Medicine in the Developed Countries 371
US HHSs Supports Personalized Medicine 371
Personalized Medicine in the USA 372
Personalized Medicine in the EU 372
UK National Health Service and Medical Genetics 373
Personalized Medicine in the Developing Countries 373
Advantages and Limitations of Personalized Medicine 374
Summary 376
16.pdf 377
Chapter 16 377
Ethical and Regulatory Aspects of Personalized Medicine 377
Introduction to Ethical Issues 377
Ethical Issues of Pharmacogenetics 377
Ethical Aspects of Genetic Information 378
Ethical Issues of Whole Genome Analysis 378
Ethical Aspects of Direct-to-Consumer (DTC) Genetic Services 379
Privacy Issues in Personalized Medicine 381
Genetic Information Nondiscrimination Act in the USA 381
Genotype-Specific Clinical Trials 382
Social Issues in Personalized Medicine 382
Race and Personalized Medicine 383
Regulatory Aspects 385
CLSI Guideline for the Use of RNA Controls in Gene Expression Assays 386
Microarray Quality Control Project 386
Regulatory Aspects of Pharmacogenetics 387
Regulation of DTC Genetic Testing 388
FDA and Pharmacogenomics 389
FDA Guidance for Pharmacogenomic Data Submissions 389
Joint Guidelines of the FDA and EU Regulators for Pharmacogenomics 390
Pharmacogenomic Information in Drug Labels 390
FDA guidelines for Pharmacogenomics-Based Dosing 391
FDA and Validation of Biomarkers 391
FDA and Predictive Medicine 392
FDA Regulation of Multivariate Index Assays 393
Evaluation of Companion Diagnostics/Therapeutic for Cancer 395
Summary 395
17.pdf 396
18.pdf 407
Chapter 18 407
Future of Personalized Medicine 407
Introduction 407
Ongoing Genomic Projects 408
Understanding the Genetic Basis of Diseases 408
Personal Genome Project 408
Genome-Wide Association Studies 409
The 1000 Genomes Project 410
Genomics of Aging in a Genetically Homogeneous Population 411
Translational Science and Personalized Medicine 411
Translation of Genomic Research into Genetic Testing for Healthcare 411
Long-Term Behavioral Effects of Personal Genetic Testing 412
Drivers for the Development of Personalized Medicine 413
Evolution of Medicine as a Driver for Personalized Therapy Markets 414
Personalized Predictive Medicine 414
Opportunities and Challenges 415
Prospects and Limitations of Genetic Testing 415
Challenges in Delivery of Personalized Medicine 416
Pharmacotyping 417
Concluding Remarks about the Future of Personalized Medicine 417
Summary 418
BM2.pdf 419
Anchor 1 419
| Erscheint lt. Verlag | 29.8.2009 |
|---|---|
| Zusatzinfo | XXVI, 430 p. |
| Verlagsort | New York |
| Sprache | englisch |
| Themenwelt | Medizin / Pharmazie ► Gesundheitsfachberufe |
| Medizin / Pharmazie ► Medizinische Fachgebiete ► Pharmakologie / Pharmakotherapie | |
| Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie | |
| Naturwissenschaften ► Biologie ► Biochemie | |
| Naturwissenschaften ► Chemie | |
| Technik ► Umwelttechnik / Biotechnologie | |
| Schlagworte | Biology • Biotechnology • Cancer • Cardiovascular Disease • Diagnostics • Medicine • Molecular Biology • Proteomics • Research • Translation |
| ISBN-10 | 1-4419-0769-6 / 1441907696 |
| ISBN-13 | 978-1-4419-0769-1 / 9781441907691 |
| Haben Sie eine Frage zum Produkt? |
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Dateiformat: PDF (Portable Document Format)
Mit einem festen Seitenlayout eignet sich die PDF besonders für Fachbücher mit Spalten, Tabellen und Abbildungen. Eine PDF kann auf fast allen Geräten angezeigt werden, ist aber für kleine Displays (Smartphone, eReader) nur eingeschränkt geeignet.
Systemvoraussetzungen:
PC/Mac: Mit einem PC oder Mac können Sie dieses eBook lesen. Sie benötigen dafür einen PDF-Viewer - z.B. den Adobe Reader oder Adobe Digital Editions.
eReader: Dieses eBook kann mit (fast) allen eBook-Readern gelesen werden. Mit dem amazon-Kindle ist es aber nicht kompatibel.
Smartphone/Tablet: Egal ob Apple oder Android, dieses eBook können Sie lesen. Sie benötigen dafür einen PDF-Viewer - z.B. die kostenlose Adobe Digital Editions-App.
Buying eBooks from abroad
For tax law reasons we can sell eBooks just within Germany and Switzerland. Regrettably we cannot fulfill eBook-orders from other countries.
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