Cancer as a Metabolic Disease

Informationen zum Autor THOMAS N. SEYFRIED, PhD , has taught and conducted research in the fields of neurogenetics, neurochemistry, and cancer for more than twenty-five years at Yale University and Boston College. He has published more than 150 scientific articles and book chapters and is on the editorial boards of Nutrition & Metabolism, Journal of Lipid Research, Neurochemical Research , and ASN Neuro . Klappentext A groundbreaking new approach to understanding, preventing, and treating cancer Supported by evidence from more than 1,000 scientific and clinical studies, this groundbreaking book demonstrates that cancer is a metabolic disease and, more importantly, that it can be more effectively managed and prevented when it is recognized as such. Moreover, the book provides detailed evidence that the traditional view of cancer as a genetic disease has been largely responsible for the failure to develop effective therapies and preventive strategies. Cancer as a Metabolic Disease reevaluates the origins of cancer based on the latest research findings as well as several decades of studies exploring the defects in tumor cell energy metabolism. Author Thomas Seyfried is a biochemical geneticist who has been investigating the lipid biochemistry of cancer for thirty years. In this book, he carefully establishes why approaching cancer as a metabolic disease leads to better understanding and management of all aspects of the disease, including inflammation, vascularization, cell death, drug resistance, and genomic instability. In addition, the book explores: Origin of metastasis New treatment strategies that target tumor cell energy metabolism, including the ketogenic diet More effective prevention strategies in light of the metabolic origin of cancer Case studies and perspectives from the point of view of physicians, patients, and caregivers Throughout the book, tables, figures, and graphs summarize key information and clarify complex concepts. In addition, the renowned cancer biochemist Peter Pedersen from Johns Hopkins Medical School also provides a historical perspective on the importance of the information presented in his foreward to the book. Cancer as a Metabolic Disease is essential reading for all cancer researchers and clinicians as well as public health professionals. By treating cancer as a metabolic disease, the book sets readers on a new, more promising path to understanding the origins of cancer and developing new, more effective strategies to treat and prevent it. Zusammenfassung The book addresses controversies related to the origins of cancer and provides solutions to cancer management and prevention. It expands upon Otto Warburg's well-known theory that all cancer is a disease of energy metabolism. However, Warburg did not link his theory to the "hallmarks of cancer" and thus his theory was discredited. Inhaltsverzeichnis Forword xiii Preface xv 1. Images of Cancer 1 How Cancer is Viewed 2 References 13 2. Confusion Surrounds the Origin of Cancer 15 The Oncogenic Paradox 18 Hallmarks of Cancer 18 Reassessment 26 References 27 3. Cancer Models 31 Problems with Some Cancer Models 31 Animal Charges as a Major Impediment to Cancer Research 38 Problems with Tumor Histological Classification 39 Personal Perspective on Cancer 44 References 45 4. Energetics of Normal Cells and Cancer Cells 47 Metabolic Homeostasis 47 The Constancy of the ¿ G 'ATP 54 ATP Production in Normal Cells and Tumor Cells 55 Energy Production Through Glucose Fermentation 57 Glutaminolysis with or without Lactate Production 61 Transamination Reactions 64 TCA Cycle, Substrate-Level Phosphorylation 66 Cholesterol Synthesis and Hy...

List of contents

Forword xiii
 
Preface xv
 
1. Images of Cancer 1
 
How Cancer is Viewed 2
 
References 13
 
2. Confusion Surrounds the Origin of Cancer 15
 
The Oncogenic Paradox 18
 
Hallmarks of Cancer 18
 
Reassessment 26
 
References 27
 
3. Cancer Models 31
 
Problems with Some Cancer Models 31
 
Animal Charges as a Major Impediment to Cancer Research 38
 
Problems with Tumor Histological Classification 39
 
Personal Perspective on Cancer 44
 
References 45
 
4. Energetics of Normal Cells and Cancer Cells 47
 
Metabolic Homeostasis 47
 
The Constancy of the G ATP 54
 
ATP Production in Normal Cells and Tumor Cells 55
 
Energy Production Through Glucose Fermentation 57
 
Glutaminolysis with or without Lactate Production 61
 
Transamination Reactions 64
 
TCA Cycle, Substrate-Level Phosphorylation 66
 
Cholesterol Synthesis and Hypoxia 67
 
Summary 67
 
References 68
 
5. Respiratory Dysfunction in Cancer Cells 73
 
Normal Mitochondria 74
 
Morphological Defects in Tumor Cell Mitochondria 77
 
Proteomic Abnormalities in Tumor Cell Mitochondria 79
 
Lipidomic Abnormalities in Tumor Cell Mitochondria 81
 
Cardiolipin: A Mitochondrial-Specific Lipid 83
 
Cardiolipin and Abnormal Energy Metabolism in Tumor Cells 85
 
Complicating Influence of the In Vitro Growth Environment on Cardiolipin Composition and Energy Metabolism 92
 
Mitochondrial Uncoupling and Cancer 97
 
Cancer Cell Heat Production and Uncoupled Mitochondria 98
 
Personal Perspective 99
 
Summary 100
 
References 101
 
6. The Warburg Dispute 107
 
Sidney Weinhouse's Criticisms of the Warburg Theory 108
 
Alan Aisenberg's Criticisms of the Warburg Theory 110
 
Sidney Colowick's Assessment of the Aisenberg Monograph 113
 
Apples and Oranges 114
 
References 116
 
7. Is Respiration Normal in Cancer Cells? 119
 
Pseudo-Respiration 119
 
How Strong is the Scientific Evidence Showing that Tumor Cells can Produce Energy Through OxPhos? 124
 
OxPhos Origin of ATP in Cancer Cells Reevaluated 124
 
What About OxPhos Expression in Other Tumors? 127
 
The Pedersen Review on Tumor Mitochondria and the Bioenergetics of Cancer Cells 128
 
References 129
 
8. Is Mitochondrial Glutamine Fermentation a Missing Link in the Metabolic Theory of Cancer? 133
 
Amino Acid Fermentation can Maintain Cellular Energy Homeostasis During Anoxia 133
 
Evidence Suggesting that Metastatic Mouse Cells Derive Energy from Glutamine Fermentation 134
 
Fermentation Energy Pathways can Drive Cancer Cell Viability Under Hypoxia 138
 
Competing Explanations for the Metabolic Origin of Cancer 141
 
Chapter Summary 143
 
References 143
 
9. Genes, Respiration, Viruses, and Cancer 145
 
Does Cancer have a Genetic Origin? 145
 
Respiratory Insufficiency as the Origin of Cancer 150
 
Germline Mutations, Damaged Respiration, and Cancer 154
 
Somatic Mutations and Cancer 158
 
Revisiting the Oncogene Theory 160
 
Mitochondrial Mutations and the Absence or Presence of Cancer 163
 
Viral Infection, Damaged Respiration, and the Origin of Cancer 165
 
Summary 168
 
References 168
 
10. Respiratory Insufficiency, the Retrograde Response, and the Origin of Cancer 177
 
The Retrograde (RTG) Response: An Epigenetic System Responsible for Nuclear Genomic Stability 177

Report

"This book offers a refreshing perspective for anyone wanting to get a comprehensive background on the newer emerging interest in targeting cancer metabolism for therapy." (Doody's, 11 January 2013)
 
"For the first time, an entire issue is being devoted to a review article based on a recent medical book. This is a departure from our usual format, but I think you will agree that this topic warrants the detailed treatment we have given it . . .This book should be required reading for all scientifically literate people who are involved in the cancer problem." (Advances in Cancer Treatment, 1 October 2012)

Product details

• Authors: Thomas Seyfried, Seyfried Thomas
• Publisher: Blackwell Scientific Publishers Ltd
• Languages: English
• Product format: Hardback
• Released: 31.07.2012
• EAN: 9780470584927
• ISBN: 978-0-470-58492-7
• Dimensions: 164 mm x 243 mm x 31 mm
• Subjects: Natural sciences, medicine, IT, technology > Medicine > General; Chemie, Medizin, Onkologie, Neurowissenschaften, Life Sciences, Neuroscience, Biowissenschaften, Chemische Biologie, chemistry, Medical Science, Biochemie u. Chemische Biologie, Biochemistry (Chemical Biology), Medizinische Onkologie, Medical Oncology