Molecular Medicine E-Book

Jens Kurreck

• Herausgeber: Wiley-VCH
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 1120

Veröffentlichungsjahr: 2015

Beschreibung

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.

Leseprobe

CONTENTS

Cover

Related Titles

Title Page

Copyright

Dedication

Preface

Acknowledgments

Chapter 1: Introduction

1.1 The Basics of Molecular Medicine

1.2 The Human Cell

1.3 DNA Replication and Gene Expression

1.4 Biological Communication

1.5 The Immune System

References

Chapter 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

References

Chapter 3: Genetic Disorders

3.1 Single-Gene Disorders

3.2 Polygenic Disorders

References

Chapter 4: Molecular Oncology

4.1 Molecular Biology of Breast Cancer and Its Clinical Implications

4.2 Lung Cancer

4.3 Hepatocellular Carcinoma

4.4 Molecular Biology of Colorectal Cancer and Its Clinical Implications

4.5 Molecular Biology of Renal Cell Carcinoma

4.6 Molecular Biology of Prostate Cancer

4.7 Molecular Biology of Hematological Malignancies

References

Chapter 5: Molecular Virology

5.1 The Basics of Virology

5.2 Vaccination

5.3 Detection of Viruses

5.4 Antiviral Therapy

5.5 Prions

References

Chapter 6: Bacteria and Eukaryotic Pathogens

6.1 Bacteria

6.2 Eukaryotic Pathogens

References

Chapter 7: Genomics and Proteomics

7.1 Whole Genome Sequencing

7.2 The Human Genome

7.3 Proteomics

References

Chapter 8: Genetic Testing

8.1 Types of Genetic Tests

8.2 Chromosome Abnormalities

8.3 Molecular Diagnosis

References

Chapter 9: Pharmacogenetics/Pharmacogenomics

9.1 Uptake and Transport of Drugs

9.2 Drug Metabolism

9.3 Drug Targeting

9.4 Drug Toxicity and Hypersensitivity

9.5 Drug Development and Individual Pharmacotherapy

References

Chapter 10: Recombinant Protein Drugs

10.1 Production of Recombinant Proteins

10.2 Classes of Recombinant Drugs

References

Chapter 11: Gene Therapy

11.1 Types of Gene Therapy

11.2 Methods of Gene Transfer

11.3 Tissue Specificity of Gene Transfer and Gene Expression

11.4 Applications of Gene Therapy

11.5 Future Prospects

References

Chapter 12: Stem Cells

12.1 Embryonic Stem Cells

12.2 Adult Stem Cells

12.3 Induced Pluripotent Stem Cells

12.4 Transdifferentiation and Direct Reprogramming

12.5 Differentiation of Stem Cells

12.6 Medical Applications of Stem Cells

References

Chapter 13: Antisense, Ribozyme, and RNA Interference Strategies

13.1 Antisense Oligonucleotides

13.2 Ribozymes

13.3 RNA Interference

13.4 MicroRNAs

References

Chapter 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

Chapter 15: Ethics in Molecular Medicine

15.1 The Basis of Bioethics

15.2 Fields of Application

Abbreviations

Glossary

Index

End User License Agreement

List of Tables

Table 1.1

Table 1.2

Table 1.3

Table 1.4

Table 2.1

Table 3.1

Table 3.2

Table 3.3

Table 4.1

Table 4.2

Table 4.3

Table 4.4

Table 5.1

Table 5.2

Table 5.3

Table 5.4

Table 6.1

Table 6.2

Table 7.1

Table 7.2

Table 7.3

Table 8.1

Table 9.1

Table 10.1

Table 10.2

Table 10.3

Table 10.4

Table 10.5

Table 11.1

Table 11.2

Table 12.1

Table 13.1

Table 13.2

Table 14.1

List of Illustrations

Fig. 1.1

Fig. 1.2

Fig. 1.3

Fig. 1.4

Fig. 1.5

Fig. 1.6

Fig. 1.7

Fig. 1.8

Fig. 1.9

Fig. 1.10

Fig. 1.11

Fig. 1.12

Fig. 1.13

Fig. 1.14

Fig. 1.15

Fig. 1.16

Fig. 1.17

Fig. 1.18

Fig. 1.19

Fig. 1.20

Fig. 1.21

Fig. 1.22

Fig. 1.23

Fig. 1.24

Fig. 1.25

Fig. 1.26

Fig. 1.27

Fig. 1.28

Fig. 1.29

Fig. 1.30

Fig. 1.31

Fig. 1.32

Fig. 1.33

Fig. 2.1

Fig. 2.2

Fig. 2.3

Fig. 2.4

Fig. 2.5

Fig. 2.6

Fig. 2.7

Fig. 2.8

Fig. 2.9

Fig. 2.10

Fig. 2.11

Fig. 2.12

Fig. 2.13

Fig. 2.14

Fig. 2.15

Fig. 2.16

Fig. 2.17

Fig. 2.18

Fig. 2.19

Fig. 2.20

Fig. 2.21

Fig. 2.22

Fig. 2.23

Fig. 2.24

Fig. 2.25

Fig. 3.1

Fig. 3.2

Fig. 3.3

Fig. 3.4

Fig. 3.5

Fig. 3.6

Fig. 3.7

Fig. 3.8

Fig. 3.9

Fig. 3.10

Fig. 3.11

Fig. 3.12

Fig. 3.13

Fig. 3.14

Fig. 4.1

Fig. 4.2

Fig. 4.3

Fig. 4.4

Fig. 4.5

Fig. 4.6

Fig. 4.7

Fig. 4.8

Fig. 4.9

Fig. 4.10

Fig. 4.11

Fig. 4.12

Fig. 4.13

Fig. 4.14

Fig. 4.15

Fig. 4.16

Fig. 4.17

Fig. 4.18

Fig. 4.19

Fig. 5.1

Fig. 5.2

Fig. 5.3

Fig. 5.4

Fig. 5.5

Fig. 5.6

Fig. 5.7

Fig. 5.8

Fig. 5.9

Fig. 5.10

Fig. 5.11

Fig. 5.12

Fig. 5.13

Fig. 5.14

Fig. 5.15

Fig. 5.16

Fig. 5.17

Fig. 5.18

Fig. 5.19

Fig. 5.20

Fig. 6.1

Fig. 6.2

Fig. 6.3

Fig. 6.4

Fig. 6.5

Fig. 6.6

Fig. 6.7

Fig. 6.8

Fig. 6.9

Fig. 6.10

Fig. 6.11

Fig. 6.12

Fig. 7.1

Fig. 7.2

Fig. 7.3

Fig. 7.4

Fig. 7.5

Fig. 7.6

Fig. 7.7

Fig. 7.8

Fig. 7.9

Fig. 7.10

Fig. 7.11

Fig. 7.12

Fig. 7.13

Fig. 7.14

Fig. 7.15

Fig. 7.16

Fig. 7.17

Fig. 8.1

Fig. 8.2

Fig. 8.3

Fig. 8.4

Fig. 8.5

Fig. 8.6

Fig. 8.7

Fig. 8.8

Fig. 8.9

Fig. 8.10

Fig. 9.1

Fig. 9.2

Fig. 9.3

Fig. 9.4

Fig. 9.6

Fig. 9.5

Fig. 9.7

Fig. 9.8

Fig. 9.9

Fig. 9.10

Fig. 9.11

Fig. 9.12

Fig. 10.1

Fig. 10.2

Fig. 10.3

Fig. 10.4

Fig. 10.5

Fig. 10.7

Fig. 10.6

Fig. 10.8

Fig. 10.9

Fig. 10.10

Fig. 10.11

Fig. 10.12

Fig. 10.13

Fig. 10.14

Fig. 10.15

Fig. 10.16

Fig. 10.17

Fig. 10.18

Fig. 10.19

Fig. 11.1

Fig. 11.2

Fig. 11.3

Fig. 11.4

Fig. 11.5

Fig. 11.6

Fig. 11.7

Fig. 11.8

Fig. 11.9

Fig. 11.10

Fig. 11.11

Fig. 11.12

Fig. 11.13

Fig. 11.14

Fig. 11.15

Fig. 11.16

Fig. 11.17

Fig. 11.18

Fig. 11.19

Fig. 11.20

Fig. 12.1

Fig. 12.2

Fig. 12.3

Fig. 12.4

Fig. 12.5

Fig. 12.6

Fig. 12.7

Fig. 12.8

Fig. 12.9

Fig. 12.10

Fig. 12.11

Fig. 12.12

Fig. 12.13

Fig. 12.14

Fig. 13.1

Fig. 13.2

Fig. 13.3

Fig. 13.4

Fig. 13.5

Fig. 13.6

Fig. 13.7

Fig. 13.8

Fig. 13.9

Fig. 13.10

Fig. 13.11

Fig. 13.12

Fig. 13.13

Fig. 13.14

Fig. 13.15

Fig. 13.16

Fig. 13.17

Fig. 13.18

Fig. 13.19

Fig. 13.20

Fig. 13.21

Fig. 13.22

Fig. 13.23

Fig. 13.24

Fig. 13.25

Fig. 13.26

Fig. 13.27

Fig. 13.28

Fig. 13.29

Fig. 13.30

Fig. 14.1

Fig. 14.2

Fig. 14.3

Fig. 14.4

Fig. 14.5

Fig. 14.6

Fig. 14.7

Fig. 14.8

Fig. 14.9

Fig. 14.10

Fig. 14.11

Fig. 14.12

Fig. 14.13

Fig. 14.14

Fig. 14.15

Fig. 15.1

Fig. 15.2

Fig. 15.3

Guide

Cover

Table of Contents

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Molecular Medicine

An Introduction

Jens Kurreck and Cy Aaron Stein

All books published by Wiley-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Library of Congress Card No.: applied for

British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library.

Bibliographic information published by the Deutsche Nationalbibliothek

The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at <http://dnb.d-nb.de>.

© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany

All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law

Print ISBN: 978-3-527-33189-5

ePDF ISBN: 978-3-527-67508-1

ePub ISBN: 978-3-527-67507-4

Mobi ISBN: 978-3-527-67511-1

Dedication

Dedicated to Ferdinand Hucho and John J. Rossi for their contributions to the life sciences, and most importantly, for being extraordinarily well-respected, decent, honorable human beings.

Preface

Molecular medicine is one of the hottest, most dynamic areas in all the life sciences and combines the disciplines of biology, biochemistry, human biology, and pharmacology, in addition to basic and clinical medicine. Knowledge of the molecular sources of disease has and will continue to pave the way for the development of novel diagnostic procedures and therapeutic strategies to treat inherited or acquired diseases. The expanding repertory of therapeutic approaches finally makes it possible to address diseases that hitherto have been untreatable. Molecular medicine will without doubt change our disease treatment paradigms; rather than employing standard therapies for every individual and adjusting treatment based on observed efficacy and side effects, personalized approaches based on specific constitutional features of the distressed individual will become possible.

In recent years, many universities worldwide have established bachelors and masters degree programs to study molecular medicine. In addition, molecular medicine has become an indispensible component of well-established curriculums. Courses of study in medicine, (molecular) biology, biochemistry, human biology, and biotechnology have frequently been offered. We thus had the sense that it was time to assemble an up-to-date introduction to the entire spectrum of molecular medicine, one written in a clear and uniform style. Numerous color figures and expositions of clinical relevance will, we hope, also ensure a systematic introduction to the topic.

This textbook primarily addresses undergraduates and lecturers. It is based on our experience in teaching courses in molecular medicine for many years, in laboratory research, and in medical practice. We assume that students who use this textbook have at least some basic knowledge of molecular and cell biology. If not, we recommend that students first consult appropriate introductory textbooks such as Principles of Biochemistry by Voet et al. or Molecular Biology of the Cell by Alberts et al. Although this textbook is primarily written for undergraduates, we also hope that medical and graduate students and researchers in the field of molecular medicine will also benefit from it.

For many reasons, writing a book on molecular medicine is a challenging task. First, there is no common consent on just what molecular medicine actually is. We view molecular medicine as a discipline that investigates normal and pathological cellular processes at the molecular level. Such in-depth analysis will help us to better understand the causes of disease, improve diagnosis, and develop novel therapeutic strategies. This understanding of molecular medicine has led us to the selection of the topics that are covered in this book.

The broad range of topics poses a second challenge, as no two-author team can possibly be experts in all areas of molecular medicine. However, we chose not to edit a book composed of individual specific articles, each written by an expert in a particular field in his or her own style. Instead, we have attempted to present a homogeneous textbook in a uniform and consistent style.

Numerous cross-references will help the reader to understand the complex interdependencies between the different fields of molecular medicine. For example, the monoclonal antibody Herceptin not only provides a comparatively new treatment option for aggressive breast cancer but is also a recombinant protein drug that is challenging to produce. Its successful therapeutic use represents one of the paradigmatic applications of pharmacogenetic testing.

Finally, the dynamics of the field of molecular medicine required us to assemble a textbook with the most up-to-date information possible. An accompanying Web site – http://www.wileyvch.de/home/molecular_medicine – will contain figures and figure legends from the book, in addition to regular updates on the latest developments in the field.

This textbook is divided into chapters, each of which can be viewed as one lecture of a one semester course on molecular medicine. The sections are structured in a logical order. However, each chapter can also stand alone as an introduction to a single topic, for example, gene therapy or stem cell technology. Cross-references will help the reader to find sections in the book that should be consulted for an in-depth understanding of the topic.

The textbook commences with a short general introduction to molecular and cellular biology and then describes some selected methods widely used in modern life science research. Several chapters deal with the molecular causes of disease, and established as well as new diagnostic approaches are also described. Viral, bacterial, or eukaryotic pathogen infections are also covered, as these are a major cause of suffering and death worldwide, and require continuous improvements in therapeutics for the management of emerging pathogens and drug resistance. The outline of novel therapeutic approaches for the treatment of cancer and genetic disorders developed in the era of molecular medicine will certainly leave the reader impressed by the dynamism of this field: Drugs based on recombinant proteins, particularly monoclonal antibodies, have already become an important element in clinical practice. Timely topics such as the newest advances in gene therapy, stem cell research, and RNA technologies will be introduced with numerous helpful figures. The book will conclude with a chapter on the ethical dimensions of molecular medicine.

Every chapter is accompanied by recommendations for further reading. Rather than providing an exhaustive list of bibliographical references that would be of limited use for most students, we selected educationally valuable review articles for each topic. While we initially intended to choose current articles, we also found older reviews that can provide excellent introductions to various subjects. In addition, the reference lists are intended to help students to begin navigating through the jungle known as the modern scientific literature.

We hope that the readers will enjoy our journey through the field of molecular medicine and share our enthusiasm for this fascinating subject. We would be very pleased if our textbook helps prepare you for working in this exciting field.

Acknowledgments

This book would not have been possible without the help of many people. We are particularly thankful to Erik Wade for reading all the chapters and providing valuable suggestions. We also thank Anke Wagner for her comments on several chapters. We also want to thank our (JK) student Derya Günes for her chapter revisions. Additional thanks goes to Mary Houlemarde and Tonya Nickens for their support, and to Daniela Castanotto for her unfailing good humor, common sense, and help in probing some of the more complex issues of this narrative. A big thanks goes to Harry Kurreck for proofreading all the chapters and giving valuable comments.

We want to thank the team at Wiley, Waltraud Wüst, Anne Chassin du Guerny, Gregor Cicchetti, and Andreas Sendtko, for their advice and assistance. A special thank goes to our graphic designer Anke Wagner for converting our quirky sketches into illustrative figures.

It is impossible for two scientists to cover the whole field of molecular medicine in depth. We are, therefore, thankful to our expert colleagues for their valuable comments on specific topics: Thomas Bock, Toni Cathomen, Henry Fechner, Anja Pöhlein, Roland Lauster, and Daniela Castanotto. In addition, we want to thank Tatjana Schütze for support with the graphical representation of protein structures. We also want to thank our research groups for their enthusiasm about molecular medicine.

Last but not least, we express our most heartfelt appreciation and thanks to our families for their patience when we spent far too much time writing this book. Therefore, this book is for Harry, Marianne, Malte, Paul, and Anke; for Myra, Allison and Warren; Lauren and Brian; and Lily Leigh and Margot Nicole.

May 2015

Jens Kurreck, Berlin

Cy Aaron Stein, Duarte

1Introduction

Contents List

The Basics of Molecular Medicine

Topics of Molecular Medicine

Stages of Drug Development

The Human Cell

Organelles

Cell Cycle

Apoptosis

DNA Replication and Gene Expression

DNA Replication

Mutations

Transcription

Epigenetic Regulation of Gene Expression

Translation

Protein Degradation

Biological Communication

Neurotransmitters

Hormones

Signal Transduction

The Immune System

The Innate Immune System

The Adaptive Immune System

Summary

Molecular medicine is a highly dynamic field of life science research that uses interdisciplinary approaches to understand normal and pathological cellular processes at the molecular level. The findings of basic research have entered clinical practice, as new diagnostic assays and novel therapeutic strategies focus not only on the symptoms but also on the causes of disease.

The development of drugs is a long-term and expensive process that starts with basic and preclinical research. A candidate drug must then successfully pass through three types of clinical trial in humans before a novel agent can be approved for therapeutic purposes.

The eukaryotic cell is compartmentalized into several cellular organelles by intracellular membranes. The nucleus harbors the genetic material, mitochondria are the cellular power plants, and the endoplasmic reticulum and the Golgi apparatus are responsible for the glycosylation and sorting of proteins.