Molecular Medicine - An Introduction

Molecular Medicine: An Introduction

Contents

Preface

1: Introduction

1.1 The Basics of Molecular Medicine

1.1.1 Topics of Molecular Medicine

1.1.2 Stages of Drug Development

1.2 The Human Cell

1.2.1 Organelles

1.2.1.1 The Nucleus

1.2.1.2 Mitochondria

1.2.1.3 Endoplasmic Reticulum and Golgi Apparatus

1.2.1.4 Peroxisome and Lysosome

1.2.2 Cell Cycle

1.2.3 Apoptosis

1.3 DNA Replication and Gene Expression

1.3.1 DNA Replication

1.3.2 Mutations

1.3.3 Transcription

1.3.4 Epigenetic Regulation of Gene Expression

1.3.5 Translation

1.3.6 Protein Degradation

1.4 Biological Communication

1.4.1 Neurotransmitters

1.4.2 Hormones

1.4.3 Signal Transduction

1.5 The Immune System

1.5.1 The Innate Immune System

1.5.1.1 The Complement System

1.5.2 The Adaptive Immune System

1.5.2.1 Cellular Immunity

1.5.2.2 Humoral Immunity

References

2: Methods in Molecular Medicine

2.1 DNA Microarrays

2.2 Quantitative Polymerase Chain Reaction

2.3 Next-Generation Sequencing

2.4 Animal Models in Biomedical Research

2.5 Additional Methods

2.5.1 Fluorescence Microscopy

2.5.2 Flow Cytometry and Fluorescence-Activated Cell Sorting

2.5.3 Surface Plasmon Resonance

References

3: Genetic Disorders

3.1 Single-Gene Disorders

3.1.1 Autosomal Dominant Disorders

3.1.1.1 Familial Hypercholesterolemia

3.1.1.2 Polycystic Kidney Disease

3.1.1.3 Marfan's Syndrome

3.1.1.4 Huntington's Disease

3.1.2 Autosomal Recessive Disorders

3.1.2.1 Cystic Fibrosis

3.1.2.2 Tay-Sachs Disease

3.1.2.3 Phenylketonuria

3.1.2.4 Xeroderma Pigmentosum

3.1.3 X-Linked Recessive Disorders

3.1.3.1 Red-Green Color Blindness

3.1.3.2 Duchenne and Becker Muscular Dystrophy

3.1.4 Mitochondriopathies

3.2 Polygenic Disorders

3.2.1 Asthma

3.2.2 Diabetes Mellitus

References

4: Molecular Oncology

4.1 Molecular Biology of Breast Cancer and Its Clinical Implications

4.1.1 Intrinsic Subtypes of Breast Cancer

4.1.1.1 Luminal

4.1.1.2 Subclassification of TNBC

4.1.2 Molecular Profiling of Breast Cancer

4.1.3 Signaling Pathways

4.1.3.1 The Role of the Estrogen Pathway in Breast Cancer

4.1.3.2 Endocrine Therapy Resistance

4.1.3.3 The mTOR/PI3K Pathway and Endocrine Resistance

4.1.3.4 The CDK 4/6 Pathway

4.1.3.5 HER2 Pathway and HER2 Targeted Therapy

4.1.4 Angiogenesis Pathway

4.1.4.1 PARP Inhibitors

4.1.5 Other Biological Therapies/Approaches

4.2 Lung Cancer

4.2.1 Genetic Alterations in Non-Small Cell Lung Cancer

4.2.1.1 Epidermal Growth Factor Receptor

4.2.1.2 Anaplastic Lymphoma Kinase

4.2.1.3 Kirsten Rat Sarcoma (KRAS)

4.2.1.4 The Proto-Oncogene ROS1

4.2.1.5 The Proto-Oncogene BRAF

4.2.1.6 The Human Epidermal Growth Factor Receptor 2 (HER2)

4.2.1.7 The RET Proto-Oncogene

4.2.1.8 The MET Proto-Oncogene

4.2.1.9 Phosphatidylinositol-3-Kinase (PI3K)

4.2.1.10 Immune Checkpoint Inhibition

4.3 Hepatocellular Carcinoma

4.3.1 Risk Factors for Hepatocellular Carcinoma

4.3.2 Molecular Biology of Hepatocellular Carcinoma

4.3.3 Development of Sorafenib for the Treatment of Hepatocellular Carcinoma

4.3.4 Complexity of Cancer

4.4 Molecular Biology of Colorectal Cancer and Its Clinical Implications

4.4.1 Colorectal Cancer Carcinogenesis

4.4.1.1 Chromosomal Instability Pathway

4.4.1.2 Microsatellite Instability Pathway

4.4.1.3 CpG Island Methylator Phenotype (CIMP) Pathway

4.4.2 Hereditary Colorectal Cancers

4.4.2.1 Familial Adenomatous Polyposis

4.4.2.2 Management of FAP Patients

4.4.2.3 Hereditary Non-Polyposis Colorectal Cancer

4.4.2.4 Management of HNPCC-Associated Germline Mutation Carriers

4.4.2.5 MUTYH-Associated Colorectal Cancer

4.4.2.6 Management of MAP Patients

4.4.3 Clinical Impact of Molecular Markers on the Management of Colorectal Cancer

4.4.3.1 MSI-H Status and Colorectal Cancer

4.4.3.2 Epidermal Growth Factor Receptor Pathway Targeting and Colorectal Cancer

4.4.3.3 RAS Mutations and Response to Anti-EGFR Therapy

4.4.3.4 BRAF Mutations and Colorectal Cancer

4.5 Molecular Biology of Renal Cell Carcinoma

4.5.1 Biology of Clear Cell Renal Cell Carcinoma

4.5.2 Approved Drugs for the Treatment of Clear Cell Renal Cell Carcinoma

4.5.3 Investigational Approaches for the Treatment of Clear Cell Renal Cell Carcinoma

4.5.4 Biology and Treatment of Papillary Renal Cell Carcinoma

4.5.5 Biology and Treatment of Chromophobe Renal Cell Carcinoma

4.5.6 Further Subtypes of Renal Cell Carcinoma

4.6 Molecular Biology of Prostate Cancer

4.6.1 Genes Associated with Hereditary Prostate Cancer

4.6.2 Tumor Suppressor Genes in Sporadic Prostate Cancer

4.6.3 Oncogenes

4.7 Molecular Biology of Hematological Malignancies

4.7.1 The Importance of Cytogenetics in Diagnosis and Treatment Decision-Making

4.7.2 Recognition of a Genetic Basis for the Hematological Malignancies

4.7.3 Targeted Therapeutics for Hematological Malignancies

4.7.4 Risk-Adapted Therapies

4.7.5 Epigenetics and Hematological Malignancies

4.7.6 The Unknown Unknowns - The Future of Molecular Oncology

References

5: Molecular Virology

5.1 The Basics of Virology

5.1.1 Human Immunodeficiency Virus

5.1.2 Hepatitis B Virus

5.1.3 Influenza Virus

5.2 Vaccination

5.2.1 Live Vaccines

5.2.2 Recombinant Virus Vaccines

5.2.3 Inactivated Virus Vaccines

5.2.4 Subunit Vaccines

5.2.5 DNA Vaccines

5.2.6 HIV Vaccines

5.3 Detection of Viruses

5.3.1 Cytopathic Effects

5.3.2 Electron Microscopy

5.3.3 Hemagglutination Assay

5.3.4 Enzyme-Linked Immunosorbent Assay (ELISA)

5.3.5 Indirect ELISA

5.3.6 Polymerase Chain Reaction (PCR)

5.3.7 Antiviral Susceptibility Testing

5.4 Antiviral Therapy

5.4.1 Human Immunodeficiency Virus (HIV)

5.4.2 Hepatitis C Virus

5.4.3 Influenza Virus

5.4.4 Other Viruses

5.5 Prions

References

6: Bacteria and Eukaryotic Pathogens

6.1 Bacteria

6.1.1 Pathogenic Bacteria

6.1.2 Bacterial Vaccines, Diagnostic, and Antibiotics

6.1.2.1 Vaccines

6.1.2.2 Diagnostic

6.1.2.3 Antibiotics

6.2 Eukaryotic Pathogens

References

7: Genomics and Proteomics

7.1 Whole Genome Sequencing

7.1.1 Cloning of a Genome

7.1.2 Mapping and Assembly of the Genome

7.1.3 Sequencing of a Large Genome

7.2 The Human Genome

7.2.1 Sequencing of the Human Genome

7.2.2 The International HapMap Project

7.2.3 The 1000 Genomes Project and the Personal Genome Project

7.2.4 Encyclopedia of DNA Elements (ENCODE)

7.3 Proteomics

7.3.1 Two-Dimensional Gel Electrophoresis and Mass Spectrometry

7.3.2 Quantitative and Shotgun Proteomics

7.3.3 Structural Proteomics

References

8: Genetic Testing

8.1 Types of Genetic Tests

8.1.1 Postnatal Genetic Tests

8.1.2 Prenatal Genetic Tests

8.2 Chromosome Abnormalities

8.2.1 Conventional Karyotyping

8.2.2 Fluorescence In Situ Hybridization

8.2.3 Comparative Genomic Hybridization

8.3 Molecular Diagnosis

8.3.1 PCR-Based Methods

8.3.2 DNA Sequencing

8.3.3 DNA Microarray-Based Methods

References

9: Pharmacogenetics/Pharmacogenomics

9.1 Uptake and Transport of Drugs

9.2 Drug Metabolism

9.2.1 Cytochrome P450 Enzymes

9.2.2 Other Drug Metabolizing Enzymes

9.3 Drug Targeting

9.4 Drug Toxicity and Hypersensitivity

9.5 Drug Development and Individual Pharmacotherapy

References

10: Recombinant Protein Drugs

10.1 Production of Recombinant Proteins

10.1.1 Bacteria

10.1.2 Yeast and Other Fungi

10.1.3 Insect Cells

10.1.4 Mammalian Cells

10.1.5 Transgenic Animals and Plants

10.2 Classes of Recombinant Drugs

10.2.1 Monoclonal Antibodies

10.2.2 Hormones

10.2.3 Growth Factors

10.2.4 Fusion Proteins

10.2.5 Cytokines

10.2.6 Blood Coagulation Factors: Anticoagulants and Thrombolytics

10.2.7 Therapeutic Enzymes

10.2.8 Recombinant Vaccines

References

11: Gene Therapy

11.1 Types of Gene Therapy

11.2 Methods of Gene Transfer

11.2.1 Retroviral Vectors

11.2.2 Adenoviral Vectors

11.2.3 Adeno-Associated Virus Vectors

11.2.4 Nonviral Gene Transfer

11.3 Tissue Specificity of Gene Transfer and Gene Expression

11.4 Applications of Gene Therapy

11.4.1 Gene Therapy of Monogenic Diseases

11.4.2 Gene Therapy of Cancer

11.4.3 Other Diseases

11.5 Future Prospects

References

12: Stem Cells

12.1 Embryonic Stem Cells

12.1.1 Generation and Properties of Embryonic Stem Cells

12.1.2 Therapeutic Cloning

12.2 Adult Stem Cells

12.3 Induced Pluripotent Stem Cells

12.3.1 Generation of Induced Pluripotent Stem Cells

12.3.2 Properties of Induced Pluripotent Stem Cells

12.4 Transdifferentiation and Direct Reprogramming

12.5 Differentiation of Stem Cells

12.6 Medical Applications of Stem Cells

12.6.1 Adult Stem Cell Therapies

12.6.2 Pluripotent Stem Cells for Biomedical Research

12.6.3 Therapeutic Applications of Pluripotent Stem Cells

12.6.3.1 Diabetes

12.6.3.2 Heart Disease

12.6.3.3 Neurodegenerative Diseases

12.6.3.4 Combinations of Stem Cell and Gene Therapy

12.6.3.5 Clinical Trials

References

13: Antisense, Ribozyme, and RNA Interference Strategies

13.1 Antisense Oligonucleotides

13.1.1 Mechanism of Action of Antisense Oligonucleotides

13.1.2 Development and Stabilization of Antisense Oligonucleotides

13.1.3 Clinical Applications

13.2 Ribozymes

13.2.1 Classification of Ribozymes

13.2.2 Development of Ribozymes for Medical Applications

13.2.3 Clinical Applications of Ribozymes

13.3 RNA Interference

13.3.1 Mechanism of RNA Interference

13.3.2 Nonspecific Side Effects

13.3.3 Delivery

13.3.4 Preclinical Applications of RNA Interference

13.3.5 Clinical Trials

13.4 MicroRNAs

13.4.1 The Biology of MicroRNAs

13.4.2 MicroRNAs and Disease

References

14: Aptamers

14.1 Selection of Aptamers

14.2 Modifications of Aptamers

14.3 Clinical Development of Aptamers

14.4 Decoy and Immunostimulatory Oligonucleotides

References

15: Ethics in Molecular Medicine

15.1 The Basis of Bioethics

15.2 Fields of Application

15.2.1 Genetic Testing and the Right ``Not to Know´´

15.2.2 Stem Cell Research

15.2.3 Preimplantation Genetic Diagnosis

Abbreviations

Glossary

Index

EULA