Molecular medicine: how science works
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| Format: | Book |
| Language: | English |
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[2023]
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| Online Access: | Inhaltsverzeichnis Klappentext |
| Physical Description: | XXXIV, 700 Seiten Illustrationen |
| ISBN: | 9783031271328 |
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| 245 | 1 | 0 | |a Molecular medicine |b how science works |c Carsten Carlberg, Eunike Velleuer, Ferdinand Molnár |
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| 300 | |a XXXIV, 700 Seiten |b Illustrationen | ||
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| 650 | 4 | |a Biomedical Research | |
| 650 | 4 | |a Genomics | |
| 650 | 4 | |a Cancers | |
| 650 | 4 | |a Immunology | |
| 650 | 4 | |a Nutrition | |
| 650 | 4 | |a Physiology | |
| 650 | 4 | |a Medicine-Research | |
| 650 | 4 | |a Biology-Research | |
| 650 | 4 | |a Genomics | |
| 650 | 4 | |a Cancer | |
| 650 | 4 | |a Immunology | |
| 650 | 4 | |a Nutrition | |
| 650 | 4 | |a Physiology | |
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| 700 | 1 | |a Molnár, Ferdinand |e Verfasser |0 (DE-588)1205043675 |4 aut | |
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| adam_text | Contents 1 The Human Genome and Its Variations ................................................. 1 Migration of Honw Sapiens and the Diversity of Human Populations........................................................................... 1 1.2 Genetic Variants of the Human Genome ...................................... 1.3 Measuring HumanGenetic Variations ........................................... Additional Reading.................................................................................... 4 7 12 1.1 2 Gene Expression and Chromatin ............................................................. 2.1 Central Dogma of Molecular Biology ........................................... 2.2 Nucleosomes: Central Units of Chromatin ................................... 2.3 Chromatin Structure and Epigenetics............................................ 2.4 Epigenetics Enables Gene Expression .......................................... 2.5 Gene Regulation in the Context of Nuclear Architecture ............ Additional Reading.................................................................................... 3 Basal Transcriptional Machinery ............................................................. 3.1 Core Promoter ................................................................................ 3.2 TATA Box and Other Core Promoter Elements ........................... 3.3 Genome-Wide Core Promoter Identification................................. 3.4 TFIID and MED as Paradigms of Multiprotein Complexes ........ Additional
Reading.................................................................................... 4 Transcription Factors and Signal Transduction ................................... 4.1 Site-Specific Transcription Factors and Their Domains ............... 4.2 Classification of Transcription Factors........................................... 4.3 Activation of Transcription Factors ............................................... 4.4 Inflammatory Signaling via NFkB ................................................. 4.5 Sensing Cellular Stress via P53...................................................... Additional Reading.................................................................................... 13 13 17 20 22 25 28 29 29 32 34 37 45 47 47 53 56 59 63 66
Contents x 5.1 The Nuclear Receptor Superfamily ................................................ 5.2 Molecular Interactions of Nuclear Receptors ................................. 5.3 Nuclear Receptors as Nutrient Sensors .......................................... 5.4 integration of Lipid Metabolism by PPARs, LXRsand FXR .... 5.5 Coordination of the Immune Response by VDR ........................... Additional Reading..................................................................................... 67 67 70 76 78 82 85 DNA Methylation .......................................................................................... 87 6.1 Cytosines and Their Methylation .................................................. 6.2 The DNA Methylome..................................................................... 6.3 CTCF and Genetic Imprinting........................................................ 6.4 DNA Methylation and Disease ...................................................... Additional Reading.................................................................................... 87 90 93 97 99 A Key Transcription Factor Family: Nuclear Receptors..................... 5 6 7 8 9 Histone Modifications .................................................................................. æl 7.1 Histones and Their Modifications.................................................. 7.2 Genome-Wide Interpretation of the Histone Code ...................... 7.3 Chromatin Modifiers....................................................................... 7.4 Gene Regulation via Chromatin Modifiers
................................. Additional Reading.................................................................................... Ю1 103 1θ9 Hl И4 Chromatin Remodeling and Organization .............................................. И7 8.1 Nucleosome Positioning at Promoters ........................................... 8.2 Chromatin Remodeling .................................................................. 8.3 Organization of Chromatin in the Nucleus .................................. Additional Reading.................................................................................... H7 H9 121 128 Regulatory Impact of Non-coding RNA .................................................. 131 131 133 138 142 144 9.1 Non-Coding RNAs ........................................................................ 9.2 miRNAs and Their Regulatory Potential ...................................... 9.3 Long ncRNAs ................................................................................ 9.4 Enhancer RNAs.............................................................................. Additional Reading.................................................................................... 10 Genome-Wide Principles of Gene Regulation ........................................ 10.1 Gene Regulation in the Context of Big Biology ........................... 10.2 Epigenetic Methods ....................................................................... 10.3 Integrating Epigenome-Wide Datasets........................................... 10.4 Genome-Wide Understanding of Epigenetics
............................... Additional Reading.................................................................................... 11 Epigenetics in Development ......................................................................... 11.1 11.2 11.3 11.4 11.5 Epigenetic Changes During Early Human Development.............. The Epigenetic Landscape............................................................. Epigenetic Dynamics During Differentiation ............................... Epigenetics of Blood Cell Differentiation ..................................... Neuronal Development: The Role of Epigenetics......................... 145 145 148 153 154 159 161 161 164 169 171 173
Contents 12 11.6 Epigenetic Basis of Memory ......................................................... Additional Reading.................................................................................... 177 179 Epigenetics and Aging ................................................................................ 181 181 185 187 191 195 12.1 Transgenerational Epigenetic Inheritance .................................... 12.2 Population Epigenetics................................................................... 12.3 Epigenetics of Aging ..................................................................... 12.4 Epigenetics of the Circadian Clock................................................ Additional Reading.................................................................................... 13 14 Epigenetics and Disease.............................................................................. 197 13.1 Epigenetic Reprograming in Cancer.............................................. 197 13.2 Epigenetic Basis of Neurological Diseases ................................... 202 13.3 Epigenetic Therapy of Diseases .................................................... 206 Additional Reading.................................................................................... 210 Cells and Tissues of the Immune System................................................ 14.1 Global Burden of Infectious Diseases .......................................... 14.2 Innate and Adaptive Immunity ..................................................... 14.3 Hematopoiesis
................................................................................ 14.4 Primary and Secondary Structures of the Immune System .......... Additional Reading.................................................................................... 15 Innate Immunity and Inflammation........................................................ 15.1 Receptors for PAMPs and DAMPs ................................................ 15.2 Myeloid and Lymphoid Cells of Innate Immunity ....................... 15.3 Role of Epigenetics in Immune Responses .................................. 15.4 Mechanisms of Phagocytosis and Inflammation........................... Additional Reading.................................................................................... 16 Adaptive Immunity and Antigen Receptor Diversity........................... 16.1 Classes and Responses of Adaptive Immune Cells ..................... 16.2 Lymphocyte Maturation ................................................................. 16.3 Mechanisms of Antigen Receptor Diversity ................................. Additional Reading.................................................................................... 17 211 211 213 218 221 227 229 229 232 239 243 251 253 253 260 262 269 В Cell Immunity: BCRs, Antibodies and Their Effector Functions................................................................................................. 271 17.1 Structure and Diversity of Antibodies and BCRs ......................... 17.2 BCR
Signaling................................................................................ 17.3 Humoral Adaptive Immune Response .......................................... Additional Reading.................................................................................... 18 xi Antigen-Presenting Celis and MHCs ....................................................... 18.1 Antigen-Presenting Cells ............................................................... 18.2 MHC Proteins and the HLA Locus ................................................ 18.3 MHC Pathways .............................................................................. Additional Reading.................................................................................... 271 277 279 287 289 289 292 296 300
Contents 19 T Cell Immunity: TCRs andTheir Effector Functions ........................ 19.1 TCR Signaling................................................................................ 19.2 T Cell Effector Functions............................................................... 19.3 Th Cells .......................................................................................... 19.4 Cytotoxic T Cells ......................................................................... Additional Reading.................................................................................... 20 Immunity to Bacterial Pathogens and the Microbiome ....................... 20.1 Principles of Immune Responses to Infections ............................. 20.2 Immune Responses to Bacteria ...................................................... 20.3 Emerging Microbial Pathogens...................................................... 20.4 Immunity to the Microbiome.......................................................... Additional Reading.................................................................................... 21 Immunity to Viral Pathogens and the Virome ....................................... 21.1 Principles of Immune Responses to Viruses ................................. 21.2 Chronic Virus Infections and Emerging Viral Pathogens ............ 21.3 Influenza.......................................................................................... 21.4 COVID-19 ...................................................................................... Additional
Reading.................................................................................... 22 Tolerance and Transplantation Immunology ........................................ 22.1 Central and Peripheral Tolerance .................................................. 22.2 Graft Rejection ............................................................................... 22.3 Immunosuppression ....................................................................... Additional Reading.................................................................................... 23 Immunological Hypersensitivities: Allergy and Autoimmunity........ 23.1 Classification of Hypersensitivities................................................ 23.2 Immunity of Allergies ................................................................... 23.3 Type 2 and 3 Hypersensitivities .................................................... 23.4 T Cell-Mediated Autoimmunity .................................................... 23.5 The Equilibrium Model of Immunity ............................................ Additional Reading.................................................................................... 24 Introduction to Cancer ................................................................................ 24.1 The Global Burden of Cancer ........................................................ 24.2 Categorization and Diagnosis of Tumors....................................... 24.3 Crucial Transitions in Cancer ........................................................ 24.4 Causes of
Cancer............................................................................. 24.5 Cancer Prevention ........................................................................... Additional Reading.................................................................................... 25 Oncogenes, Signal Transduction and the Hallmarks of Cancer........ 25.1 Cellular Transformation ................................................................. 25.2 Activating Oncogenes in Signal Transduction Pathways.............. 25.3 Oncogenic Translocations and Amplifications ............................. 301 301 3θ5 309 315 3^9 321 321 326 333 332 3^ 345 345 349 33$ 359 3^4 365 36$ 3^9 322 3$θ 381 3$1 3$4 394 392 403 406 407 407 411 414 415 417 421 423 423 425 429
Contents xiii 25.4 The Hallmarks of Cancer Concept ............................................... 431 Additional Reading.................................................................................... 433 435 26.1 p53—A Master Example Tumor Suppressor................................ 435 26.2 Tumor Suppressors and Oncogenes in Cell Cycle Control ......... 437 26.3 Tumor Suppressor Inhibition and Cancer Onset.......................... 439 Additional Reading................................................................................... 443 26 Ћ։тог Suppressor Genes and Cell Fate Control.................................... 27 Multistep Ihmorigenesis and GenomeInstability................................... 27.1 Characteristics of Tumor Growth ................................................. 27.2 Multistep Tumorigenesis ............................................................... 27.3 Genome Instability ........................................................................ 27.4 Cancer Driver Mutations and Genes.............................................. Additional Reading.................................................................................... 28 Cancer Genomics .......................................................................................... 28.1 Human Genetic Variation and Cancer Susceptibility.................. 28.2 The Cancer Genome ....................................................................... 28.3 Cancer Genome Projects ............................................................... Additional
Reading.................................................................................... 445 445 448 451 454 457 459 459 461 462 468 469 29.1 Epigenetic Mechanisms of Cancer ............................................... 469 29.2 DNA Methylation and Cancer....................................................... 472 29.3 Chromatin Changes and Cancer .................................................... 475 Additional Reading.................................................................................... 478 29 Cancer Epigenomics...................................................................................... 30 Aging and Cancer .......................................................................................... 30.1 Central Role of Aging During Chronic Diseases ........................ 30.2 The Hallmarks of Aging................................................................. 30.3 Telomeres and Replicative Immortality ........................................ Additional Reading.................................................................................... 31 Tumor Microenvironment........................................................................... 31.1 The Impact of the Wound Healing Program for Cancer ............ 31.2 Cell Types of the Tumor Microenvironment ................................. 31.3 Inducing Angiogenesis................................................................... 31.4 Tumor-Promoting Inflammation .................................................... 31.5 Deregulating Cellular Energetics
................................................ Additional Reading.................................................................................... 32 Metastasis and Cachexia ............................................................................. 32.1 The Metastatic Cascade ................................................................ 32.2 Epithelial-Mesenchymal Transition ............................................. 32.3 Metastatic Colonization ................................................................ 32.4 Cachexia........................................................................................ Additional Reading.................................................................................... 479 479 482 485 488 489 489 492 496 498 499 502 505 505 508 511 513 518
xiv Contents Cancer Immunology................................................................................. 33.1 Outline of Cancer Immunity .......................................................... 33.2 Recognition of Cancer Antigens ..................................................... 33.3 Monoclonal Antibodies in Cancer Immunotherapy ..................... 33.4 Immune Cell Therapies .................................................................. Additional Reading..................................................................................... 519 519 525 527 531 534 34 Architecture of Cancer Therapies 34.1 Classical Cancer Treatments ......................................................... 34.2 Targeted Therapies ........................................................................ 34.3 Precision Oncology......................................................................... Additional Reading..................................................................................... 535 535 539 543 ^47 33 35 Nutrition and Common Diseases............................................................ 549 35.1 Evolution of Human Nutrition........................................................ 549 35.2 Principles of Metabolism ................................................................ 552 35.3 Dietary Molecules and Their Sensing ........................................... 554 35.4 Nutrition and Metabolic Diseases.................................................. 559 35.5 Impact of Physical Activity ............................................................
561 Additional Reading.................................................................................... 563 36 Interference of the Human Genome with Nutrients ........................... 36.1 Human Genetic Adaptions.............................................................. 36.2 Genetic Adaption to Dietary Changes ........................................... 36.3 Regulatory SNPs and Quantitative Traits....................................... 36.4 Definition of Nutrigenomics .......................................................... 36.5 Personal Omics Profiles .................................................................. Additional Reading.................................................................................... 565 565 567 569 571 575 578 37 Nutritional Epigenetics, Signaling and Aging ..................................... 37.1 Intermediary Metabolism and Epigenetic Signaling .................... 37.2 Aging and Conserved Nutrient-Sensing Pathways ........................ 37.3 Neuroendocrine Regulation of Aging............................................. 37.4 Principles of Insulin Signaling ...................................................... 37.5 Central Role of FOXO Transcription Factors ............................... 37.6 Calorie Restriction from Yeast to Mammals ................................. 37.7 Cellular Energy Status Sensing by SIRTs and AMPK.................. Additional Reading.................................................................................... 579 579 584 587 588 591 594 596 600 38 Chronic Inflammation and Metabolic Stress
....................................... 38.1 Acute and Chronic Inflammation .................................................. 38.2 Reverse Cholesterol Transport and Inflammation......................... 38.3 Sensing Metabolic Stress via the ER ............................................. Additional Reading.................................................................................... 603 603 608 610 613
Contents 39 Obesity.............................................................................................................. 39.1 Definition of Obesity .................................................................... 39.2 Adipogenesis ................................................................................. 39.3 Inflammation in Adipose Tissue ................................................... 39.4 Energy Homeostasis and Hormonal Regulation of Food Uptake.................................................................................. 625 39.5 Genetics of Obesity........................................................................ Additional Reading................................................................................... 40 Insulin Resistance and Diabetes ................................................................ 40.1 Glucose Homeostasis .................................................................... 40.2 Insulin Resistance in Skeletal Muscle and Liver.......................... 40.3 ß Cell Failure................................................................................. 40.4 Definition of Diabetes.................................................................... 40.5 Failure of Glucose Homeostasis in T2D and Its Treatment......... 40.6 Genetics and Epigenetics of T2D ................................................. Additional Reading.................................................................................... 41 Heart Disease and the Metabolic Syndrome............................................ 41.1 Hypertension
.................................................................................. 41.2 Mechanisms of Atherosclerosis..................................................... 41.3 Lipoproteins and Dyslipidemias ................................................... 41.4 Whole Body’s Perspective of the Metabolic Syndrome............... 41.5 Metabolic Syndrome in Key Metabolic Organs ........................... 41.6 Genetics and Epigenetics of the Metabolic Syndrome................. Additional Reading................................................................................... XV 615 615 617 622 629 631 633 634 637 639 642 644 648 651 653 653 655 658 662 667 671 673 42.1 Genetics, Epigenetics and Environment........................................ 42.2 Central Relation of Epigenetics and Immunity ............................ Additional Reading................................................................................... 675 675 679 681 Glossary................................................................................................................... 683 42 Epigenetics, Inflammation and Disease ....................................................
Carsten Cariberg · Eunike Velleuer ■ Ferdinand Molnár Molecular Medicine How Science Works The fascinating area ofmolecular medicine provides a molecular and cellular descrip tion of health and disease. Starting with the understanding of gene regulation and epigenetics, i.e., the interplay of transcription factors and chromatin, this book will provide an fundamental basis of nearly all processes in physiology, both in health as well as in most common disorders, such as cancer, diabetes as well as in autoimmune diseases. Most non-communicable human diseases have a genetic (= inherited) as well as an epigenetic component. The later one is based on our lifestyle choices and environmental exposures. Many common diseases, such as type 2 diabetes, can be explained only to some 20% via a genetic predisposition. We cannot change the genes that we are born with but we can take care of the remaining 80% being primarily based on our epigenome. Therefore, there is a high level of individual responsibility for staying healthy. Thus, not only biologists and biochemists should be aware of this topic, but all students of biomedical disciplines will benefit from being introduced into the concepts of molecular medicine. This will provide them with a good basis for their specialized disciplines of modern life science research. The book is subdivided into 42 chapters that are linked to a series of lecture courses in “Molecular Medicine and Genetics”, “Molecular Immunology”, “Cancer Biology” and “Nutrigenomics” that is given by one of us (C. Carlberg) in different forms since 2002 at the
University of Ea stern Finland in Kuopio. This book represents an up dated version and fusion of the books textbooks “Mechanisms of Gene Regulation: How Science Works” (isbn 978-3-030-52321-3), “Human Epigenetics: How Science Works” (isbn 978-3-030-22907-8). “Molecular Immunology: How Science Works” (isbn 978-3-031-04024-5), “Cancer Biology: How Science Works” (isbn 978-3-03075699-4) and “Nutrigenomics: How Science Works” (isbn 978-3-030-36948-4). By combining basic understanding of cellular mechanism with clinical examples, the authors hope to make this textbook a personal experience. A glossary in the ap pendix will explain the major specialists terms.
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Contents 1 The Human Genome and Its Variations . 1 Migration of Honw Sapiens and the Diversity of Human Populations. 1 1.2 Genetic Variants of the Human Genome . 1.3 Measuring HumanGenetic Variations . Additional Reading. 4 7 12 1.1 2 Gene Expression and Chromatin . 2.1 Central Dogma of Molecular Biology . 2.2 Nucleosomes: Central Units of Chromatin . 2.3 Chromatin Structure and Epigenetics. 2.4 Epigenetics Enables Gene Expression . 2.5 Gene Regulation in the Context of Nuclear Architecture . Additional Reading. 3 Basal Transcriptional Machinery . 3.1 Core Promoter . 3.2 TATA Box and Other Core Promoter Elements . 3.3 Genome-Wide Core Promoter Identification. 3.4 TFIID and MED as Paradigms of Multiprotein Complexes . Additional
Reading. 4 Transcription Factors and Signal Transduction . 4.1 Site-Specific Transcription Factors and Their Domains . 4.2 Classification of Transcription Factors. 4.3 Activation of Transcription Factors . 4.4 Inflammatory Signaling via NFkB . 4.5 Sensing Cellular Stress via P53. Additional Reading. 13 13 17 20 22 25 28 29 29 32 34 37 45 47 47 53 56 59 63 66
Contents x 5.1 The Nuclear Receptor Superfamily . 5.2 Molecular Interactions of Nuclear Receptors . 5.3 Nuclear Receptors as Nutrient Sensors . 5.4 integration of Lipid Metabolism by PPARs, LXRsand FXR . 5.5 Coordination of the Immune Response by VDR . Additional Reading. 67 67 70 76 78 82 85 DNA Methylation . 87 6.1 Cytosines and Their Methylation . 6.2 The DNA Methylome. 6.3 CTCF and Genetic Imprinting. 6.4 DNA Methylation and Disease . Additional Reading. 87 90 93 97 99 A Key Transcription Factor Family: Nuclear Receptors. 5 6 7 8 9 Histone Modifications . æl 7.1 Histones and Their Modifications. 7.2 Genome-Wide Interpretation of the Histone Code . 7.3 Chromatin Modifiers. 7.4 Gene Regulation via Chromatin Modifiers
. Additional Reading. Ю1 103 1θ9 Hl И4 Chromatin Remodeling and Organization . И7 8.1 Nucleosome Positioning at Promoters . 8.2 Chromatin Remodeling . 8.3 Organization of Chromatin in the Nucleus . Additional Reading. H7 H9 121 128 Regulatory Impact of Non-coding RNA . 131 131 133 138 142 144 9.1 Non-Coding RNAs . 9.2 miRNAs and Their Regulatory Potential . 9.3 Long ncRNAs . 9.4 Enhancer RNAs. Additional Reading. 10 Genome-Wide Principles of Gene Regulation . 10.1 Gene Regulation in the Context of Big Biology . 10.2 Epigenetic Methods . 10.3 Integrating Epigenome-Wide Datasets. 10.4 Genome-Wide Understanding of Epigenetics
. Additional Reading. 11 Epigenetics in Development . 11.1 11.2 11.3 11.4 11.5 Epigenetic Changes During Early Human Development. The Epigenetic Landscape. Epigenetic Dynamics During Differentiation . Epigenetics of Blood Cell Differentiation . Neuronal Development: The Role of Epigenetics. 145 145 148 153 154 159 161 161 164 169 171 173
Contents 12 11.6 Epigenetic Basis of Memory . Additional Reading. 177 179 Epigenetics and Aging . 181 181 185 187 191 195 12.1 Transgenerational Epigenetic Inheritance . 12.2 Population Epigenetics. 12.3 Epigenetics of Aging . 12.4 Epigenetics of the Circadian Clock. Additional Reading. 13 14 Epigenetics and Disease. 197 13.1 Epigenetic Reprograming in Cancer. 197 13.2 Epigenetic Basis of Neurological Diseases . 202 13.3 Epigenetic Therapy of Diseases . 206 Additional Reading. 210 Cells and Tissues of the Immune System. 14.1 Global Burden of Infectious Diseases . 14.2 Innate and Adaptive Immunity . 14.3 Hematopoiesis
. 14.4 Primary and Secondary Structures of the Immune System . Additional Reading. 15 Innate Immunity and Inflammation. 15.1 Receptors for PAMPs and DAMPs . 15.2 Myeloid and Lymphoid Cells of Innate Immunity . 15.3 Role of Epigenetics in Immune Responses . 15.4 Mechanisms of Phagocytosis and Inflammation. Additional Reading. 16 Adaptive Immunity and Antigen Receptor Diversity. 16.1 Classes and Responses of Adaptive Immune Cells . 16.2 Lymphocyte Maturation . 16.3 Mechanisms of Antigen Receptor Diversity . Additional Reading. 17 211 211 213 218 221 227 229 229 232 239 243 251 253 253 260 262 269 В Cell Immunity: BCRs, Antibodies and Their Effector Functions. 271 17.1 Structure and Diversity of Antibodies and BCRs . 17.2 BCR
Signaling. 17.3 Humoral Adaptive Immune Response . Additional Reading. 18 xi Antigen-Presenting Celis and MHCs . 18.1 Antigen-Presenting Cells . 18.2 MHC Proteins and the HLA Locus . 18.3 MHC Pathways . Additional Reading. 271 277 279 287 289 289 292 296 300
Contents 19 T Cell Immunity: TCRs andTheir Effector Functions . 19.1 TCR Signaling. 19.2 T Cell Effector Functions. 19.3 Th Cells . 19.4 Cytotoxic T Cells . Additional Reading. 20 Immunity to Bacterial Pathogens and the Microbiome . 20.1 Principles of Immune Responses to Infections . 20.2 Immune Responses to Bacteria . 20.3 Emerging Microbial Pathogens. 20.4 Immunity to the Microbiome. Additional Reading. 21 Immunity to Viral Pathogens and the Virome . 21.1 Principles of Immune Responses to Viruses . 21.2 Chronic Virus Infections and Emerging Viral Pathogens . 21.3 Influenza. 21.4 COVID-19 . Additional
Reading. 22 Tolerance and Transplantation Immunology . 22.1 Central and Peripheral Tolerance . 22.2 Graft Rejection . 22.3 Immunosuppression . Additional Reading. 23 Immunological Hypersensitivities: Allergy and Autoimmunity. 23.1 Classification of Hypersensitivities. 23.2 Immunity of Allergies . 23.3 Type 2 and 3 Hypersensitivities . 23.4 T Cell-Mediated Autoimmunity . 23.5 The Equilibrium Model of Immunity . Additional Reading. 24 Introduction to Cancer . 24.1 The Global Burden of Cancer . 24.2 Categorization and Diagnosis of Tumors. 24.3 Crucial Transitions in Cancer . 24.4 Causes of
Cancer. 24.5 Cancer Prevention . Additional Reading. 25 Oncogenes, Signal Transduction and the Hallmarks of Cancer. 25.1 Cellular Transformation . 25.2 Activating Oncogenes in Signal Transduction Pathways. 25.3 Oncogenic Translocations and Amplifications . 301 301 3θ5 309 315 3^9 321 321 326 333 332 3^ 345 345 349 33$ 359 3^4 365 36$ 3^9 322 3$θ 381 3$1 3$4 394 392 403 406 407 407 411 414 415 417 421 423 423 425 429
Contents xiii 25.4 The Hallmarks of Cancer Concept . 431 Additional Reading. 433 435 26.1 p53—A Master Example Tumor Suppressor. 435 26.2 Tumor Suppressors and Oncogenes in Cell Cycle Control . 437 26.3 Tumor Suppressor Inhibition and Cancer Onset. 439 Additional Reading. 443 26 Ћ։тог Suppressor Genes and Cell Fate Control. 27 Multistep Ihmorigenesis and GenomeInstability. 27.1 Characteristics of Tumor Growth . 27.2 Multistep Tumorigenesis . 27.3 Genome Instability . 27.4 Cancer Driver Mutations and Genes. Additional Reading. 28 Cancer Genomics . 28.1 Human Genetic Variation and Cancer Susceptibility. 28.2 The Cancer Genome . 28.3 Cancer Genome Projects . Additional
Reading. 445 445 448 451 454 457 459 459 461 462 468 469 29.1 Epigenetic Mechanisms of Cancer . 469 29.2 DNA Methylation and Cancer. 472 29.3 Chromatin Changes and Cancer . 475 Additional Reading. 478 29 Cancer Epigenomics. 30 Aging and Cancer . 30.1 Central Role of Aging During Chronic Diseases . 30.2 The Hallmarks of Aging. 30.3 Telomeres and Replicative Immortality . Additional Reading. 31 Tumor Microenvironment. 31.1 The Impact of the Wound Healing Program for Cancer . 31.2 Cell Types of the Tumor Microenvironment . 31.3 Inducing Angiogenesis. 31.4 Tumor-Promoting Inflammation . 31.5 Deregulating Cellular Energetics
. Additional Reading. 32 Metastasis and Cachexia . 32.1 The Metastatic Cascade . 32.2 Epithelial-Mesenchymal Transition . 32.3 Metastatic Colonization . 32.4 Cachexia. Additional Reading. 479 479 482 485 488 489 489 492 496 498 499 502 505 505 508 511 513 518
xiv Contents Cancer Immunology. 33.1 Outline of Cancer Immunity . 33.2 Recognition of Cancer Antigens . 33.3 Monoclonal Antibodies in Cancer Immunotherapy . 33.4 Immune Cell Therapies . Additional Reading. 519 519 525 527 531 534 34 Architecture of Cancer Therapies 34.1 Classical Cancer Treatments . 34.2 Targeted Therapies . 34.3 Precision Oncology. Additional Reading. 535 535 539 543 ^47 33 35 Nutrition and Common Diseases. 549 35.1 Evolution of Human Nutrition. 549 35.2 Principles of Metabolism . 552 35.3 Dietary Molecules and Their Sensing . 554 35.4 Nutrition and Metabolic Diseases. 559 35.5 Impact of Physical Activity .
561 Additional Reading. 563 36 Interference of the Human Genome with Nutrients . 36.1 Human Genetic Adaptions. 36.2 Genetic Adaption to Dietary Changes . 36.3 Regulatory SNPs and Quantitative Traits. 36.4 Definition of Nutrigenomics . 36.5 Personal Omics Profiles . Additional Reading. 565 565 567 569 571 575 578 37 Nutritional Epigenetics, Signaling and Aging . 37.1 Intermediary Metabolism and Epigenetic Signaling . 37.2 Aging and Conserved Nutrient-Sensing Pathways . 37.3 Neuroendocrine Regulation of Aging. 37.4 Principles of Insulin Signaling . 37.5 Central Role of FOXO Transcription Factors . 37.6 Calorie Restriction from Yeast to Mammals . 37.7 Cellular Energy Status Sensing by SIRTs and AMPK. Additional Reading. 579 579 584 587 588 591 594 596 600 38 Chronic Inflammation and Metabolic Stress
. 38.1 Acute and Chronic Inflammation . 38.2 Reverse Cholesterol Transport and Inflammation. 38.3 Sensing Metabolic Stress via the ER . Additional Reading. 603 603 608 610 613
Contents 39 Obesity. 39.1 Definition of Obesity . 39.2 Adipogenesis . 39.3 Inflammation in Adipose Tissue . 39.4 Energy Homeostasis and Hormonal Regulation of Food Uptake. 625 39.5 Genetics of Obesity. Additional Reading. 40 Insulin Resistance and Diabetes . 40.1 Glucose Homeostasis . 40.2 Insulin Resistance in Skeletal Muscle and Liver. 40.3 ß Cell Failure. 40.4 Definition of Diabetes. 40.5 Failure of Glucose Homeostasis in T2D and Its Treatment. 40.6 Genetics and Epigenetics of T2D . Additional Reading. 41 Heart Disease and the Metabolic Syndrome. 41.1 Hypertension
. 41.2 Mechanisms of Atherosclerosis. 41.3 Lipoproteins and Dyslipidemias . 41.4 Whole Body’s Perspective of the Metabolic Syndrome. 41.5 Metabolic Syndrome in Key Metabolic Organs . 41.6 Genetics and Epigenetics of the Metabolic Syndrome. Additional Reading. XV 615 615 617 622 629 631 633 634 637 639 642 644 648 651 653 653 655 658 662 667 671 673 42.1 Genetics, Epigenetics and Environment. 42.2 Central Relation of Epigenetics and Immunity . Additional Reading. 675 675 679 681 Glossary. 683 42 Epigenetics, Inflammation and Disease .
Carsten Cariberg · Eunike Velleuer ■ Ferdinand Molnár Molecular Medicine How Science Works The fascinating area ofmolecular medicine provides a molecular and cellular descrip tion of health and disease. Starting with the understanding of gene regulation and epigenetics, i.e., the interplay of transcription factors and chromatin, this book will provide an fundamental basis of nearly all processes in physiology, both in health as well as in most common disorders, such as cancer, diabetes as well as in autoimmune diseases. Most non-communicable human diseases have a genetic (= inherited) as well as an epigenetic component. The later one is based on our lifestyle choices and environmental exposures. Many common diseases, such as type 2 diabetes, can be explained only to some 20% via a genetic predisposition. We cannot change the genes that we are born with but we can take care of the remaining 80% being primarily based on our epigenome. Therefore, there is a high level of individual responsibility for staying healthy. Thus, not only biologists and biochemists should be aware of this topic, but all students of biomedical disciplines will benefit from being introduced into the concepts of molecular medicine. This will provide them with a good basis for their specialized disciplines of modern life science research. The book is subdivided into 42 chapters that are linked to a series of lecture courses in “Molecular Medicine and Genetics”, “Molecular Immunology”, “Cancer Biology” and “Nutrigenomics” that is given by one of us (C. Carlberg) in different forms since 2002 at the
University of Ea stern Finland in Kuopio. This book represents an up dated version and fusion of the books textbooks “Mechanisms of Gene Regulation: How Science Works” (isbn 978-3-030-52321-3), “Human Epigenetics: How Science Works” (isbn 978-3-030-22907-8). “Molecular Immunology: How Science Works” (isbn 978-3-031-04024-5), “Cancer Biology: How Science Works” (isbn 978-3-03075699-4) and “Nutrigenomics: How Science Works” (isbn 978-3-030-36948-4). By combining basic understanding of cellular mechanism with clinical examples, the authors hope to make this textbook a personal experience. A glossary in the ap pendix will explain the major specialists terms. |
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| dewey-full | 610.72 |
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| dewey-ones | 610 - Medicine and health |
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| discipline | Biologie Medizin |
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| spelling | Carlberg, Carsten 1963- Verfasser (DE-588)1205043225 aut Molecular medicine how science works Carsten Carlberg, Eunike Velleuer, Ferdinand Molnár Cham Springer [2023] XXXIV, 700 Seiten Illustrationen txt rdacontent n rdamedia nc rdacarrier Biomedical Research Genomics Cancers Immunology Nutrition Physiology Medicine-Research Biology-Research Cancer Nutrition Molekulare Medizin (DE-588)4543844-4 gnd rswk-swf Molekulare Medizin (DE-588)4543844-4 s DE-604 Velleuer, Eunike 1980- Verfasser (DE-588)132855038 aut Molnár, Ferdinand Verfasser (DE-588)1205043675 aut Erscheint auch als Online-Ausgabe 978-3-031-27133-5 Digitalisierung UB Augsburg - ADAM Catalogue Enrichment application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034198202&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis Digitalisierung UB Augsburg - ADAM Catalogue Enrichment application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034198202&sequence=000003&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA Klappentext |
| spellingShingle | Carlberg, Carsten 1963- Velleuer, Eunike 1980- Molnár, Ferdinand Molecular medicine how science works Biomedical Research Genomics Cancers Immunology Nutrition Physiology Medicine-Research Biology-Research Cancer Nutrition Molekulare Medizin (DE-588)4543844-4 gnd |
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| title | Molecular medicine how science works |
| title_auth | Molecular medicine how science works |
| title_exact_search | Molecular medicine how science works |
| title_exact_search_txtP | Molecular medicine how science works |
| title_full | Molecular medicine how science works Carsten Carlberg, Eunike Velleuer, Ferdinand Molnár |
| title_fullStr | Molecular medicine how science works Carsten Carlberg, Eunike Velleuer, Ferdinand Molnár |
| title_full_unstemmed | Molecular medicine how science works Carsten Carlberg, Eunike Velleuer, Ferdinand Molnár |
| title_short | Molecular medicine |
| title_sort | molecular medicine how science works |
| title_sub | how science works |
| topic | Biomedical Research Genomics Cancers Immunology Nutrition Physiology Medicine-Research Biology-Research Cancer Nutrition Molekulare Medizin (DE-588)4543844-4 gnd |
| topic_facet | Biomedical Research Genomics Cancers Immunology Nutrition Physiology Medicine-Research Biology-Research Cancer Nutrition Molekulare Medizin |
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