This book provides a unique, wide-ranging description of the phenomenon of cancer and its pathological effects in diverse species including humans, domesticated and wild animals, invertebrates, and plants. The broad scope of information presented is used to construct radical new insights into biological self-regulation and explain their relevance to its disruption by cancerous growth and spread within the human body.
Mechanisms of action of carcinogenic agents, initiation, progression, metastasis, inappropriate gene expression, dormancy, latency, regression, and reasons for susceptibility and/or resistance to cancer are all considered. Also discussed are criteria for pathological diagnosis, advances in treatment, implications for public health, and pitfalls in diagnosis and interpretation of experimental results.
The book describes operational mechanisms of cancer at the levels of whole individual, organ, tissue, cell, molecular, and even atomic (quantum) scales of structural and physiological order.
Evidence is assembled from all these levels of organization to show that cancer is a dynamically changing disorder and that it is an inherent and perpetual risk of multicellular composition. This provides pragmatic new biological and clinical perspectives on malignant neoplasia. The biological insight is that it is a consequence of progressing miscommunication within a cellular society.
The clinical perspective is realistic but optimistic in reasoning that, although cancer can never be completely eradicated from human life, because it is a disorder of our intrinsic biological constitution, it can be controlled and ameliorated and even cured in a proportion of individuals.
The text is profusely illustrated with over 300 macroscopic and microscopic pictures. It will stimulate curiosity and interest specialists, as well as beginners, in many scientific disciplines and provides copious references to the medical and scientific literature supporting its conclusions.
Readers from fields as diverse as medicine, pathology, veterinary sciences, cell biology, molecular biology, developmental biology, and epidemiology will find the information the book contains thought-provoking, interesting, and useful. Additionally, specialists in occupational and environmental health and legal experts focusing on exposure to carcinogenic materials and pollution will find the contents valuable and informative.
About the Author
David Tarin is an internationally recognised physician, pathologist and scientist who has specialised in clinical diagnostic pathology and research on carcinogenesis, cancer metastasis and developmental biology. Over 6 decades he has held positions as Director of the Comprehensive Cancer Center at the University of California, San Diego; Professor of Pathology at Oxford University School of Medicine, and Professor of Pathology at the Royal Postgraduate School of Medicine, London, as well as faculty positions at other Universities. He has also worked briefly at the Department of Pathology and the Department of Zoology in the University of Helsinki, Finland and at the Austrian Cancer Institute in Vienna, Austria. In addition to the current volume, he has published 2 other books on cancer, cited below* and multiple research and clinical articles and book chapters. He has acted as an advisor to the US National Cancer Institute and to the Cancer Research Campaign of the United Kingdom. He is also widely regarded as an expert medical witness in occupational and environmental carcinogenesis and in pathological diagnosis, based on his research and clinical experience and has testified in many jurisdictions internationally.
Tissue Interactions in Carcinogenesis; Academic Press London 1972
Drug Delivery Systems Based upon the Tumour Microenvironment; Springer Japan 2020
Author(s): David Tarin
Edition: 1
Publisher: Springer
Year: 2023
Language: English
Tags: Cancer; Pathology; Oncology; Cancer Biology
Preface
The Molecular Mechanisms, Biology, Pathology and Clinical Implications of Malignant Neoplasia
Guide for Readers
Introduction
Cancer: A Remarkable Entity That Thrives on Progressive Disorder
Terminology
Contents
About the Author
Defining Cancer: Comparisons of Normal Development and Cancer Formation
1 Understanding the Nature of Cancer–General Principles
Abstract
1.1 Cancer Pathology—Analysis of Structural and Functional Disorder
1.2 Normal Tissue and Organ Composition: The Social Life of Cells, the Origins of Superorganisms and Emergent Behaviour
1.3 Mechanisms of Self-assembly of Complex Organisms: Embryological Organ Formation and Its Relevance to Cancer
1.4 Hierarchical Organisation of Multicellular Organisms
1.4.1 The Molecular Dimension
1.4.2 The Cellular Dimension
1.4.3 Tissue, Organ and Whole Organism Dimensions
1.5 Order and Disorder in Multicellular Systems: Cancerous and Non-cancerous Disease
References
2 The Phenomenon of Inappropriate Gene Expression and Its Biological and Clinical Consequences
Abstract
2.1 A Fundamental Characteristic
2.2 Defining Inappropriate Gene Expression and Its Potential Effects
2.3 Inappropriate Gene Expression in Neoplasia
2.3.1 Tumour Invasion and Metastasis: A Striking Example of Semi-coordinate Inappropriate Gene Expression
2.3.2 Inappropriate Gene Expression and Cancer Metastasis Demonstrated by Experiments with Two Isogenic Cancer Cell Lines
2.3.3 Identity of Misdirected Gene Expression Programme Causing Metastasis
2.4 Clinical Applications
2.4.1 Inappropriate Gene Expression and Cancer Diagnosis
2.5 Inappropriate Gene Expression and Paraneoplastic Syndromes: Tumour—Host Interactions
2.6 Mechanisms of Inappropriate Gene Expression and Silencing
2.7 Conclusions
2.8 Summary: Implications of Inappropriate Gene Expression for Clinical and Research Work
2.9 Appendix: Refutation of the Claim That Epithelial Mesenchymal Transition (EMT) is Needed for Metastasis
References
The Tumour “System”—Pathology and Pathophysiology of the Tumour Microenvironment
3 The Tumour System
Abstract
3.1 A Self-Propagating Heterogeneous Parasitic Entity
3.2 Differences Between Cancers and Healthy Counterpart Organs and Tissues
3.2.1 Some Basic Concepts About the Organisation of Cells and Intercellular Materials in Multicellular Organisms
3.3 Types of Tumours—Macroscopic and Microscopic Cancer Diagnosis
3.3.1 Macroscopic Characteristics
3.3.2 Microscopic Features
3.4 Histopathological Cancer Diagnosis
3.4.1 Practical Aspects of Clinical Diagnostic Work
3.4.2 Microscopic Features of Main Tumour Types
3.5 Why People Die of Cancer
3.5.1 Pathophysiological Effects of the Cancer on the Host
3.6 The Tumour as a Parasitic Organism
References
4 The Host Stroma and the Tumour Microenvironment
Abstract
4.1 Interactions Between Components of the Tumour System
4.2 The Role of the Host Stroma in Health and in Neoplasia
4.3 The Tumour Microenvironment
4.4 Cancer Pathogenesis and Progression
4.4.1 Embryological Organ Formation
4.4.2 Cancer Formation: Sequence of Microscopic Events in the Boundary Zone Between Neoplastic and Non-neoplastic Cell Populations
4.4.3 Differences Between Stromal Events in Wound Healing and in Early Neoplasia; Comparison of Healthy and Disorderly Reactions to Injurious Agents
4.4.4 Specificity of Microscopic Changes in Neoplasia
4.4.5 Implications of Stromal and Microenvironmental Changes for the Mechanisms of Carcinogenesis
4.4.6 Invasion of Adjacent Tissues
4.4.7 Matricellular Molecules, miRNA and Other Signalling Entities
4.5 Specific Examples of Clinical Conditions Showing Disturbed Microenvironmental Conditions: Dysplasia Versus Neoplasia
4.6 Why is the Histopathological Tissue Context Important?
4.7 Small Cancers Can Regress. Cancer Screening Follow up Studies and Death Rates
4.8 Diagnostic, Prognostic and Therapeutic Implications of Understanding the Cancer Microenvironment
4.9 Synthesis and Conclusions
4.10 Summary
References
Prevalence of Cancer in Nature and History of Study of the Disease
5 The Biology and Natural History of Cancer
Abstract
5.1 An Ancient Disease Ubiquitous Among Multicellular Species
5.2 Cancer in Human Populations; Geographic, Racial and Organotypic Differences
5.3 Cancer in Domestic and Farm Animals
5.4 Cancer in Captive Laboratory Animals
5.5 Cancer in Wild Animals and Plants: Cancer in the Wild
5.5.1 Mammals
5.5.2 Registry of Tumours in Other Species
5.5.3 Fish, Amphibians, Riverine and Lake Dwelling Species
5.5.4 Birds
5.5.5 Invertebrates
5.5.6 Neoplasms in Plants
5.6 Tumours and Evolution
5.7 Cancer and Embryonic Development
5.8 Summary
5.8.1 A Cosmic Perspective
References
6 Major Events in the History of Medical Understanding of Cancer
Abstract
6.1 Earliest Records—Egyptian and Greek Periods to 15th Century
6.2 Sixteenth to 19th Centuries
6.3 Nineteenth Century
6.4 Twentieth and 21st Centuries
References
Causes and Mechanisms of Cancer Formation, Invasion, Metastasis and Associated Symptoms: Clinical and Experimental Studies
7 The Behaviour of Cancers: Invasion and Metastasis I. Clinico-Pathological Aspects
Abstract
7.1 Hyperplasia, Atypia and the Pathological Significance of Carcinoma in Situ
7.1.1 Diagnostic Implications
7.2 Invasion
7.2.1 Prognostic Implications
7.3 Metastasis
7.3.1 The Major Pathways of Metastasis
7.3.2 Circulating Cancer Cells
7.3.3 The Timing of Metastasis
7.3.4 Kinetic Sequence of Events in Metastasis
7.3.5 Patterns of Metastasis
7.3.6 The Histological Structure of Metastases Reflects Their Tissue of Origin
7.3.7 Instability of the Metastatic Process
7.3.8 Is Metastasis Restricted to Tumours?
7.3.9 The Clinical Effects of Metastasis
7.3.10 Summary of the Current State of Clinical and Pathological Knowledge about of Human Cancer Metastasis
References
8 The Behaviour of Cancers: Invasion and Metastasis II. Experimental Analysis of Mechanisms
Abstract
8.1 Paradoxical Aspects of the Phenomenon of Cancer Metastasis
8.2 Methodological and Statistical Considerations
8.3 The Metastatic Drive of Tumour Cells—Cell Biological Aspects
8.3.1 Clonogenicity and Clonal Evolution
8.3.2 Cell Surface Composition
8.3.3 Cell Surface Receptors and Cognate Ligands
8.3.4 Proteases
8.4 Interactions Between Cancer Cells
8.5 Interactions Between Tumour Cells and Non-neoplastic Host Cells
8.5.1 Further Experimental Analysis of Mechanisms Determining Organ Distribution of Metastatic Deposits and of the Dormancy of Disseminated Tumour Cells
8.5.2 Interactions Between Tumour Cells and the Structural Constituents of the Extra-Cellular Matrix
8.6 Genetic Basis of the Intrinsic Metastatic Drive
8.6.1 Modulation of Gene Expression Can Affect Metastatic Behaviour
8.6.2 Transfer of Metastatic Properties with Genomic DNA
8.7 Summary
Appendix: Original data relating to Metastasis Associated Gene or Nucleic Acid (MAGNA) Sequence Isolated from Human Metastatic Cells
References
9 Causes of Cancer and Mechanisms of Carcinogenesis
Abstract
9.1 Types of Carcinogenic Agents
9.2 Chemical Carcinogenesis
9.2.1 Activation and Deactivation
9.2.2 Tobacco Smoke
9.2.3 The Roles of the International Agency for Research on Cancer (IARC) and the World Health Organisation (WHO)
9.3 Solid State Carcinogenesis: Physical (Foreign Body) Agents: Asbestos, Plastics and Other Foreign Body Implants
9.3.1 Asbestos
9.3.1.1 Composition [20–23]
9.3.1.2 Uses [22]
9.3.1.3 Health Hazards
9.3.1.4 Sources of Asbestos Fibres in the Human Environment
9.3.1.5 Carcinogenicity of Different Types of Asbestos
9.3.1.6 Presence or Absence of the Carcinogenic Agent in the Tissues
9.3.1.7 Electron Microscopy and Energy Dispersive Spectroscopy
9.3.1.8 Biopersistence/Clearance
9.3.1.9 Dosage and Susceptibility
9.3.1.10 Macroscopic and Microscopic Pathology of Tumours Induced by Asbestos
9.3.1.11 Mechanisms of Asbestos-Induced Carcinogenesis
9.3.1.12 Latent Period
9.3.1.13 Other Asbestos-Induced Diseases—Pleural Thickening, Pleural Plaques and Asbestosis [see also 29, 105, 152]
9.3.2 Foreign Body Carcinogenesis—Plastic Sheets
9.3.2.1 Observations Related to Tumours Induced by Implantation of Foreign Bodies
9.3.2.2 Biological Implications
9.3.2.3 Clinical Implications
9.4 Carcinogenesis by Infective Agents
9.4.1 Types of Agents: Prevalence of Viruses, Bacteria and Parasites
9.4.2 Infectivity and Susceptibility
9.4.3 Mechanisms of Tumour Induction
9.4.4 Factors Influencing Implementation or Abeyance of Viral Carcinogenesis
9.5 Radiation
9.6 Further Mechanistic Considerations Relevant to Carcinogens of All Types
9.6.1 Susceptibility
9.6.2 Initiation, Promotion and Progression
9.6.3 Timing of Action—Relationship to Cell Division
9.6.4 Complete Carcinogens, Co-Carcinogens and Incomplete Carcinogens
9.6.5 Relationships Between Cancer, Inflammation and Immunity
9.6.6 Mutations, Penetrance and Gene Networks
9.6.7 Carcinoma In Situ and the “Field Effect”
9.6.8 Latency
9.6.9 Progression
9.6.10 Regression and Recurrence
9.6.11 The Target of Action of Carcinogenic Agents: “Stem” Cells Versus Progenitor Cells
References
10 Paraneoplastic Syndromes
Abstract
10.1 Diversity of Systemic Effects of Malignancy
10.2 Haematological and Vascular Syndromes
10.2.1 Thrombophlebitis Migrans and Other Coagulopathies
10.2.2 Polycythaemia and Thrombocytosis
10.3 Cutaneous Disorders
10.3.1 Erythema Gyratum Repens
10.3.2 Acanthosis Nigricans
10.3.3 Dermatomyositis
10.4 Endocrine Disorders
10.4.1 Cushing’s Syndrome
10.4.2 Hypercalcaemia
10.4.3 Hypoglycaemia and Hyperglycaemia
10.4.4 Inappropriate Anti-Diuretic Hormone (IADH) Secretion
10.5 Neurological Disorders
10.5.1 General Considerations Applicable to Central and Peripheral Nervous Syndromes
10.5.2 Syndromes Affecting the Central Nervous System
10.5.3 Peripheral Neuropathies
10.6 Renal Syndromes
10.6.1 Nephrotic Syndrome
10.6.2 Haematological and Hepatic Syndromes Caused by Renal Neoplasms
10.7 Musculo-Skeletal Disorders
10.7.1 Myaesthenia Gravis
10.7.2 Arthritis, Polymyositis, Myopathies, Hypertrophic Pulmonary Osteodystrophy and Finger Clubbing
10.8 Cachexia and Fever
10.8.1 Cachexia
10.8.2 Fever
10.9 Metastasis
10.10 Therapy
10.11 Unifying Concepts and Conclusions
References
Synthesis and Significance of a New Perspective on Malignancy
11 Clinical Implications of Multi-level (Scalar) Disorganisation in Cancer
Abstract
11.1 The Concepts of Scale and Dimension in Body Organisation and Function
11.2 Diagnostic Implications of Multi-scale Dysfunction in Tumour Cells
11.2.1 At the Molecular Scale
11.2.2 At the Cellular Scale
11.2.3 At the Tissue, Organ and Whole Organism Scale
11.2.4 Prospects for Non-Invasive Diagnosis
11.3 Treatment and Palliation Implications of Molecular, Cellular, and Tissue Incoordination in Tumours
11.3.1 Clonal Dynamics and Choices of Therapeutic Strategies
11.3.2 Therapeutic Implications of Disturbances at the Molecular Scale
11.3.3 Manipulating the Pathophysiology of the Tumour Microenvironment to Enhance Cytotoxic Chemotherapy
11.3.4 Contributions of Combined Therapeutic Modalities
11.3.5 Intrinsic Body Defence Mechanisms
11.3.6 Treatment of Systemic Effects and the Value of Palliative Care
11.4 Public Health
11.4.1 Aspects Related to Chemical Carcinogenesis
11.4.2 Infectious Transmission of Cancer
11.4.3 Cancer from Ionising Radiation
11.4.4 Screening for Early Detection and Treatment of Cancer
11.5 Wider Social Implications
References
12 Understanding the Significance of Cancer in the Overall Spectrum of Disease
Abstract
12.1 Disease and Destiny—Biological Considerations
12.2 Clinical Considerations
12.3 Research Considerations
12.4 A Parting Comment—Gazing into Infinity
References
Index
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