Details

Molecular Medicine


Molecular Medicine

An Introduction
1. Aufl.

von: Jens Kurreck, Cy Aaron Stein

85,99 €

Verlag: Wiley-Blackwell
Format: EPUB
Veröffentl.: 09.11.2015
ISBN/EAN: 9783527675074
Sprache: englisch
Anzahl Seiten: 404

DRM-geschütztes eBook, Sie benötigen z.B. Adobe Digital Editions und eine Adobe ID zum Lesen.

Beschreibungen

Easy to read, yet comprehensive, this is the perfect introduction into the molecular basis of disease and the novel treatment options that have become available. The authors, Jens Kurreck and Cy Stein, have both long-standing teaching experience on the subject, one from a biologist's angle, the other with a medical background. Together, they have produced a modern textbook for courses in Molecular Medicine that incorporates modules from immunology to signaling, from virology to gene therapy, and the latest development in personalized medicine.
<p>Preface xiii</p> <p><b>1 Introduction 1</b></p> <p>1.1 The Basics of Molecular Medicine 2</p> <p>1.1.1 Topics of Molecular Medicine 2</p> <p>1.1.2 Stages of Drug Development 3</p> <p>1.2 The Human Cell 4</p> <p>1.2.1 Organelles 4</p> <p>1.2.1.1 The Nucleus 4</p> <p>1.2.1.2 Mitochondria 6</p> <p>1.2.1.3 Endoplasmic Reticulum and Golgi Apparatus 7</p> <p>1.2.1.4 Peroxisome and Lysosome 8</p> <p>1.2.2 Cell Cycle 8</p> <p>1.2.3 Apoptosis 9</p> <p>1.3 DNA Replication and Gene Expression 10</p> <p>1.3.1 DNA Replication 11</p> <p>1.3.2 Mutations 13</p> <p>1.3.3 Transcription 14</p> <p>1.3.4 Epigenetic Regulation of Gene Expression 19</p> <p>1.3.5 Translation 21</p> <p>1.3.6 Protein Degradation 24</p> <p>1.4 Biological Communication 25</p> <p>1.4.1 Neurotransmitters 26</p> <p>1.4.2 Hormones 27</p> <p>1.4.3 Signal Transduction 28</p> <p>1.5 The Immune System 30</p> <p>1.5.1 The Innate Immune System 30</p> <p>1.5.1.1 The Complement System 31</p> <p>1.5.2 The Adaptive Immune System 33</p> <p>1.5.2.1 Cellular Immunity 33</p> <p>1.5.2.2 Humoral Immunity 34</p> <p>References 36</p> <p><b>2 Methods in Molecular Medicine 37</b></p> <p>2.1 DNA Microarrays 38</p> <p>2.2 Quantitative Polymerase Chain Reaction 40</p> <p>2.3 Next-Generation Sequencing 45</p> <p>2.4 Animal Models in Biomedical Research 51</p> <p>2.5 Additional Methods 56</p> <p>2.5.1 Fluorescence Microscopy 56</p> <p>2.5.2 Flow Cytometry and Fluorescence-Activated Cell Sorting 58</p> <p>2.5.3 Surface Plasmon Resonance 59</p> <p>References 59</p> <p><b>3 Genetic Disorders 61</b></p> <p>3.1 Single-Gene Disorders 62</p> <p>3.1.1 Autosomal Dominant Disorders 64</p> <p>3.1.1.1 Familial Hypercholesterolemia 65</p> <p>3.1.1.2 Polycystic Kidney Disease 67</p> <p>3.1.1.3 Marfan’s Syndrome 67</p> <p>3.1.1.4 Huntington’s Disease 68</p> <p>3.1.2 Autosomal Recessive Disorders 69</p> <p>3.1.2.1 Cystic Fibrosis 70</p> <p>3.1.2.2 Tay–Sachs Disease 71</p> <p>3.1.2.3 Phenylketonuria 72</p> <p>3.1.2.4 Xeroderma Pigmentosum 73</p> <p>3.1.3 X-Linked Recessive Disorders 74</p> <p>3.1.3.1 Red-Green Color Blindness 75</p> <p>3.1.3.2 Duchenne and Becker Muscular Dystrophy 75</p> <p>3.1.4 Mitochondriopathies 77</p> <p>3.2 Polygenic Disorders 80</p> <p>3.2.1 Asthma 80</p> <p>3.2.2 Diabetes Mellitus 81</p> <p>References 83</p> <p><b>4 Molecular Oncology 85</b></p> <p>4.1 Molecular Biology of Breast Cancer and Its Clinical Implications 88</p> <p>4.1.1 Intrinsic Subtypes of Breast Cancer 88</p> <p>4.1.1.1 Luminal 88</p> <p>4.1.1.2 Subclassification of TNBC 89</p> <p>4.1.2 Molecular Profiling of Breast Cancer 89</p> <p>4.1.3 Signaling Pathways 89</p> <p>4.1.3.1 The Role of the Estrogen Pathway in Breast Cancer 90</p> <p>4.1.3.2 Endocrine Therapy Resistance 90</p> <p>4.1.3.3 The mTOR/PI3K Pathway and Endocrine Resistance 90</p> <p>4.1.3.4 The CDK 4/6 Pathway 90</p> <p>4.1.3.5 HER2 Pathway and HER2 Targeted Therapy 91</p> <p>4.1.4 Angiogenesis Pathway 92</p> <p>4.1.4.1 PARP Inhibitors 92</p> <p>4.1.5 Other Biological Therapies/Approaches 93</p> <p>4.2 Lung Cancer 93</p> <p>4.2.1 Genetic Alterations in Non-Small Cell Lung Cancer 93</p> <p>4.2.1.1 Epidermal Growth Factor Receptor 93</p> <p>4.2.1.2 Anaplastic Lymphoma Kinase 94</p> <p>4.2.1.3 Kirsten Rat Sarcoma (KRAS) 94</p> <p>4.2.1.4 The Proto-Oncogene ROS 1 95</p> <p>4.2.1.5 The Proto-Oncogene BRAF 95</p> <p>4.2.1.6 The Human Epidermal Growth Factor Receptor 2 (HER2) 95</p> <p>4.2.1.7 The RET Proto-Oncogene 95</p> <p>4.2.1.8 The MET Proto-Oncogene 95</p> <p>4.2.1.9 Phosphatidylinositol-3-Kinase (PI3K) 95</p> <p>4.2.1.10 Immune Checkpoint Inhibition 96</p> <p>4.3 Hepatocellular Carcinoma 96</p> <p>4.3.1 Risk Factors for Hepatocellular Carcinoma 96</p> <p>4.3.2 Molecular Biology of Hepatocellular Carcinoma 97</p> <p>4.3.3 Development of Sorafenib for the Treatment of Hepatocellular Carcinoma 97</p> <p>4.3.4 Complexity of Cancer 98</p> <p>4.4 Molecular Biology of Colorectal Cancer and Its Clinical Implications 99</p> <p>4.4.1 Colorectal Cancer Carcinogenesis 99</p> <p>4.4.1.1 Chromosomal Instability Pathway 100</p> <p>4.4.1.2 Microsatellite Instability Pathway 100</p> <p>4.4.1.3 CpG Island Methylator Phenotype (CIMP) Pathway 101</p> <p>4.4.2 Hereditary Colorectal Cancers 101</p> <p>4.4.2.1 Familial Adenomatous Polyposis 101</p> <p>4.4.2.2 Management of FAP Patients 101</p> <p>4.4.2.3 Hereditary Non-Polyposis Colorectal Cancer 102</p> <p>4.4.2.4 Management of HNPCC-Associated Germline Mutation Carriers 103</p> <p>4.4.2.5 MUTYH-Associated Colorectal Cancer 103</p> <p>4.4.2.6 Management of MAP Patients 103</p> <p>4.4.3 Clinical Impact of Molecular Markers on the Management of Colorectal Cancer 103</p> <p>4.4.3.1 MSI-H Status and Colorectal Cancer 103</p> <p>4.4.3.2 Epidermal Growth Factor Receptor Pathway Targeting and Colorectal Cancer 103</p> <p>4.4.3.3 RAS Mutations and Response to Anti-EGFR Therapy 104</p> <p>4.4.3.4 BRAF Mutations and Colorectal Cancer 104</p> <p>4.5 Molecular Biology of Renal Cell Carcinoma 105</p> <p>4.5.1 Biology of Clear Cell Renal Cell Carcinoma 105</p> <p>4.5.2 Approved Drugs for the Treatment of Clear Cell Renal Cell Carcinoma 106</p> <p>4.5.3 Investigational Approaches for the Treatment of Clear Cell Renal Cell Carcinoma 107</p> <p>4.5.4 Biology and Treatment of Papillary Renal Cell Carcinoma 108</p> <p>4.5.5 Biology and Treatment of Chromophobe Renal Cell Carcinoma 108</p> <p>4.5.6 Further Subtypes of Renal Cell Carcinoma 108</p> <p>4.6 Molecular Biology of Prostate Cancer 109</p> <p>4.6.1 Genes Associated with Hereditary Prostate Cancer 109</p> <p>4.6.2 Tumor Suppressor Genes in Sporadic Prostate Cancer 110</p> <p>4.6.3 Oncogenes 111</p> <p>4.7 Molecular Biology of Hematological Malignancies 114</p> <p>4.7.1 The Importance of Cytogenetics in Diagnosis and Treatment Decision-Making 115</p> <p>4.7.2 Recognition of a Genetic Basis for the Hematological Malignancies 117</p> <p>4.7.3 Targeted Therapeutics for Hematological Malignancies 119</p> <p>4.7.4 Risk-Adapted Therapies 120</p> <p>4.7.5 Epigenetics and Hematological Malignancies 120</p> <p>4.7.6 The Unknown Unknowns – The Future of Molecular Oncology 120</p> <p>References 121</p> <p><b>5 Molecular Virology 123</b></p> <p>5.1 The Basics of Virology 124</p> <p>5.1.1 Human Immunodeficiency Virus 127</p> <p>5.1.2 Hepatitis B Virus 130</p> <p>5.1.3 Influenza Virus 130</p> <p>5.2 Vaccination 132</p> <p>5.2.1 Live Vaccines 133</p> <p>5.2.2 Recombinant Virus Vaccines 136</p> <p>5.2.3 Inactivated Virus Vaccines 136</p> <p>5.2.4 Subunit Vaccines 137</p> <p>5.2.5 DNA Vaccines 139</p> <p>5.2.6 HIV Vaccines 139</p> <p>5.3 Detection of Viruses 139</p> <p>5.3.1 Cytopathic Effects 139</p> <p>5.3.2 Electron Microscopy 140</p> <p>5.3.3 Hemagglutination Assay 140</p> <p>5.3.4 Enzyme-Linked Immunosorbent Assay (elisa) 140</p> <p>5.3.5 Indirect ELISA 140</p> <p>5.3.6 Polymerase Chain Reaction (PCR) 140</p> <p>5.3.7 Antiviral Susceptibility Testing 142</p> <p>5.4 Antiviral Therapy 142</p> <p>5.4.1 Human Immunodeficiency Virus (HIV) 145</p> <p>5.4.2 Hepatitis C Virus 149</p> <p>5.4.3 Influenza Virus 149</p> <p>5.4.4 Other Viruses 149</p> <p>5.5 Prions 151</p> <p>References 151</p> <p><b>6 Bacteria and Eukaryotic Pathogens 153</b></p> <p>6.1 Bacteria 154</p> <p>6.1.1 Pathogenic Bacteria 155</p> <p>6.1.2 Bacterial Vaccines, Diagnostic, and Antibiotics 160</p> <p>6.1.2.1 Vaccines 160</p> <p>6.1.2.2 Diagnostic 160</p> <p>6.1.2.3 Antibiotics 160</p> <p>6.2 Eukaryotic Pathogens 166</p> <p>References 168</p> <p><b>7 Genomics and Proteomics 169</b></p> <p>7.1 Whole Genome Sequencing 170</p> <p>7.1.1 Cloning of a Genome 170</p> <p>7.1.2 Mapping and Assembly of the Genome 172</p> <p>7.1.3 Sequencing of a Large Genome 173</p> <p>7.2 The Human Genome 174</p> <p>7.2.1 Sequencing of the Human Genome 174</p> <p>7.2.2 The International HapMap Project 183</p> <p>7.2.3 The 1000 Genomes Project and the Personal Genome Project 184</p> <p>7.2.4 Encyclopedia of DNA Elements (encode) 186</p> <p>7.3 Proteomics 188</p> <p>7.3.1 Two-Dimensional Gel Electrophoresis and Mass Spectrometry 189</p> <p>7.3.2 Quantitative and Shotgun Proteomics 192</p> <p>7.3.3 Structural Proteomics 194</p> <p>References 194</p> <p><b>8 Genetic Testing 197</b></p> <p>8.1 Types of Genetic Tests 198</p> <p>8.1.1 Postnatal Genetic Tests 198</p> <p>8.1.2 Prenatal Genetic Tests 200</p> <p>8.2 Chromosome Abnormalities 202</p> <p>8.2.1 Conventional Karyotyping 203</p> <p>8.2.2 Fluorescence In Situ Hybridization 203</p> <p>8.2.3 Comparative Genomic Hybridization 205</p> <p>8.3 Molecular Diagnosis 207</p> <p>8.3.1 PCR-Based Methods 207</p> <p>8.3.2 DNA Sequencing 209</p> <p>8.3.3 DNA Microarray-Based Methods 212</p> <p>References 213</p> <p><b>9 Pharmacogenetics/Pharmacogenomics 215</b></p> <p>9.1 Uptake and Transport of Drugs 217</p> <p>9.2 Drug Metabolism 218</p> <p>9.2.1 Cytochrome P450 Enzymes 218</p> <p>9.2.2 Other Drug Metabolizing Enzymes 220</p> <p>9.3 Drug Targeting 222</p> <p>9.4 Drug Toxicity and Hypersensitivity 226</p> <p>9.5 Drug Development and Individual Pharmacotherapy 226</p> <p>References 227</p> <p><b>10 Recombinant Protein Drugs 229</b></p> <p>10.1 Production of Recombinant Proteins 232</p> <p>10.1.1 Bacteria 233</p> <p>10.1.2 Yeast and Other Fungi 234</p> <p>10.1.3 Insect Cells 235</p> <p>10.1.4 Mammalian Cells 235</p> <p>10.1.5 Transgenic Animals and Plants 236</p> <p>10.2 Classes of Recombinant Drugs 238</p> <p>10.2.1 Monoclonal Antibodies 239</p> <p>10.2.2 Hormones 245</p> <p>10.2.3 Growth Factors 247</p> <p>10.2.4 Fusion Proteins 249</p> <p>10.2.5 Cytokines 250</p> <p>10.2.6 Blood Coagulation Factors: Anticoagulants and Thrombolytics 251</p> <p>10.2.7 Therapeutic Enzymes 254</p> <p>10.2.8 Recombinant Vaccines 254</p> <p>References 255</p> <p><b>11 Gene Therapy 257</b></p> <p>11.1 Types of Gene Therapy 258</p> <p>11.2 Methods of Gene Transfer 259</p> <p>11.2.1 Retroviral Vectors 260</p> <p>11.2.2 Adenoviral Vectors 262</p> <p>11.2.3 Adeno-Associated Virus Vectors 264</p> <p>11.2.4 Nonviral Gene Transfer 266</p> <p>11.3 Tissue Specificity of Gene Transfer and Gene Expression 267</p> <p>11.4 Applications of Gene Therapy 270</p> <p>11.4.1 Gene Therapy of Monogenic Diseases 271</p> <p>11.4.2 Gene Therapy of Cancer 272</p> <p>11.4.3 Other Diseases 273</p> <p>11.5 Future Prospects 275</p> <p>References 276</p> <p><b>12 Stem Cells 277</b></p> <p>12.1 Embryonic Stem Cells 279</p> <p>12.1.1 Generation and Properties of Embryonic Stem Cells 279</p> <p>12.1.2 Therapeutic Cloning 281</p> <p>12.2 Adult Stem Cells 282</p> <p>12.3 Induced Pluripotent Stem Cells 286</p> <p>12.3.1 Generation of Induced Pluripotent Stem Cells 286</p> <p>12.3.2 Properties of Induced Pluripotent Stem Cells 288</p> <p>12.4 Transdifferentiation and Direct Reprogramming 289</p> <p>12.5 Differentiation of Stem Cells 291</p> <p>12.6 Medical Applications of Stem Cells 293</p> <p>12.6.1 Adult Stem Cell Therapies 293</p> <p>12.6.2 Pluripotent Stem Cells for Biomedical Research 296</p> <p>12.6.3 Therapeutic Applications of Pluripotent Stem Cells 299</p> <p>12.6.3.1 Diabetes 299</p> <p>12.6.3.2 Heart Disease 300</p> <p>12.6.3.3 Neurodegenerative Diseases 300</p> <p>12.6.3.4 Combinations of Stem Cell and Gene Therapy 301</p> <p>12.6.3.5 Clinical Trials 301</p> <p>References 302</p> <p><b>13 Antisense, Ribozyme, and RNA Interference Strategies 303</b></p> <p>13.1 Antisense Oligonucleotides 305</p> <p>13.1.1 Mechanism of Action of Antisense Oligonucleotides 305</p> <p>13.1.2 Development and Stabilization of Antisense Oligonucleotides 306</p> <p>13.1.3 Clinical Applications 308</p> <p>13.2 Ribozymes 311</p> <p>13.2.1 Classification of Ribozymes 311</p> <p>13.2.2 Development of Ribozymes for Medical Applications 312</p> <p>13.2.3 Clinical Applications of Ribozymes 314</p> <p>13.3 RNA Interference 315</p> <p>13.3.1 Mechanism of RNA Interference 316</p> <p>13.3.2 Nonspecific Side Effects 319</p> <p>13.3.3 Delivery 320</p> <p>13.3.4 Preclinical Applications of RNA Interference 321</p> <p>13.3.5 Clinical Trials 322</p> <p>13.4 MicroRNAs 325</p> <p>13.4.1 The Biology of MicroRNAs 325</p> <p>13.4.2 MicroRNAs and Disease 327</p> <p>References 330</p> <p><b>14 Aptamers 333</b></p> <p>14.1 Selection of Aptamers 335</p> <p>14.2 Modifications of Aptamers 337</p> <p>14.3 Clinical Development of Aptamers 339</p> <p>14.4 Decoy and Immunostimulatory Oligonucleotides 342</p> <p>References 344</p> <p><b>15 Ethics in Molecular Medicine 345</b></p> <p>15.1 The Basis of Bioethics 346</p> <p>15.2 Fields of Application 348</p> <p>15.2.1 Genetic Testing and the Right “Not to Know” 348</p> <p>15.2.2 Stem Cell Research 350</p> <p>15.2.3 Preimplantation Genetic Diagnosis 352</p> <p>Abbreviations 355</p> <p>Glossary 363</p> <p>Index 367</p>
Jens Kurreck is full Professor for Applied Biochemistry at the Berlin University of Technology (TUB), Germany. He studied biochemistry and philosophy at the Free University of Berlin (FUB) and completed his PhD at the TUB in 1998. A postdoc at Arizona State University in Tempe, AZ, USA, was followed by an assistant professorship at the FUB. From 2007 to 2009 he was Professor of Nucleic Acid Technologies at the University of Stuttgart before attaining his current position in Berlin. In 2012 he was visiting professor at the Dongseo University in Busan, Korea. His research focuses on RNA technologies, pain research and virology. He has published more than 70 papers in peer-reviewed journals and edited the book "Therapeutic Oligonucleotides". In 2005 he received the Young Scientist Lectureship Award of the European Society for Neurochemistry and a prize for his excellent teaching.<br> <br> Cy A. Stein is Professor of Oncology and Experimental Therapeutics at the City of Hope Medical Center in Duarte, CA, USA. He received a Ph.D. in chemistry from Stanford University and the M.D. degree at the Albert Einstein College of Medicine, NY, in 1982. After appointments as clinical associate and assistant professor at Columbia University, he became Professor of Medicine and Molecular Pharmacology at the Albert Einstein College of Medicine in New York (2003-2012). At the same time, he was Attending Physician and Director of Medical Genitourinary Oncology at the Montefiore Medical Center. He has published more than 200 scientific papers and received numerous awards, among them the Clinical Career Development Award of the American Cancer Society in addition to a Faculty of 1000 Biologists Selection.<br>

Diese Produkte könnten Sie auch interessieren:

The Biology of Echinostomes
The Biology of Echinostomes
von: Bernard Fried, Rafael Toledo
PDF ebook
149,79 €
Antibiotic Policies
Antibiotic Policies
von: Ian M. Gould, Jos W.M. van der Meer
PDF ebook
213,99 €
Tropical and Parasitic Infections in the Intensive Care Unit
Tropical and Parasitic Infections in the Intensive Care Unit
von: Charles Feldman, George A. Sarosi
PDF ebook
149,79 €