The majority of cancers present at a relatively advanced stage in which invasion within the primary organ is well established and metastases to lymph and distant organs are either clinically apparent or present at the microscopic level. However, it is increasingly recognized that the natural history of cancer formation is a long and complex path taking many years to develop to a clinically apparent stage in most cases. Furthermore, for most solid tumours there is a pre-invasive or intraepithelial stage of disease. This affords the opportunity for early detection and prevention of invasive disease and hence a cure. However, with this advancing knowledge comes a whole plethora of questions which will be explored in this monograph. Firstly, we need to understand the global burden of pre-invasive disease and what the public health implications might be for wide-scale screening programmes. In the western world we already have experience of screening for cervical, breast, prostate and more recently colon cancer. As well as their potential benefits these programmes have financial and psychosocial implications which need to be carefully weighed. This is especially true since many pre-invasive lesions will not progress to cancer in a individual's lifetime. In addition, there are questions concerning whether screening reduces the cancer burden or in fact distorts the survival figures through lead-time bias. Secondly, at the level of epidemiology and molecular pathogenesis there are important questions regarding the aetiology of pre-invasive lesions; an understanding of which might lead to possible chemopreventive strategies. For example, it would be helpful to know the extent to which the likelihood of developing a pre-invasive lesion is influenced by lifestyle or genetic factors and how these factors influence the risk of progression to invasive disease. At the molecular level we need to understand the pathways and molecular mechanisms, both genetic and epigenetic, by which cells achieve the capacity to invade. Thirdly, in order make clinical progress we need biomarkers to identify and risk stratify individuals with pre-invasive lesions. These biomarkers might be applied to the serum as in Prostate Specific Antigen in prostate cancer or be applied to tissue samples, such as oestrogen receptor status in breast cancer. In order to utilize biomarkers in the context of a screening programme there are issue around the invasiveness of the test as well as its positive and negative predictive value. With advances in molecular imaging there is now the exciting possibility of incorporating a molecular tag to a non-invasive imaging modality. Fourthly, in order to justify screening early detection must be coupled to a treatment strategy. If the chemopreventive agent is very well tolerated, then as well as targeting high risk groups, one might consider treatment at the population level. Aspirin is one such drug which has been extensively assessed in the context of colon cancer chemoprevention trials. Trials of aspirin chemoprevention are now being applied to other cancers such as oesophageal adenocarcinoma and since many individuals take aspirin for .chemoprevention of cardiovascular disease the cancer incidence can be ascertained in these populations. In order to understand the more general issues raised from the discussions above it is useful to consider disease specific examples. Our understanding of pre-invasive disease varies according to the organ site and there are lessons to be learned from these experiences. For example, there is now the prospect of a vaccine for cervical cancer with important questions about how this might be applied to the high incidence areas of the developing world. On the other hand, ductal carcinoma in situ is currently treated by mastectomy which is more radical than the treatment received by many women with invasive disease. Oesophageal adenocarcinoma, which is my own area of expertise is interesting because of the rapid rise in incidence in the western world and the clinically accessible pre-invasive lesion called Barrett's oesophagus. However, most cases of Barrett's oesophagus remain undiagnosed and it is not yet clear how to effectively diagnose, monitor and treat this condition without recourse to mass endoscopy with substantial cost implications. In conclusion, in an era in which preventive medicine is a major concern for consumers, health-policy makers and politicians pre-invasive disease is likely to become a major part of cancer medicine.

Integrative medicine strives to incorporate the best of complementary and conventional modalities. This book details integrative oncology, a nascent field building a rigorous evidenced-based clinical medicine, research, and educational foundation. It examines five prestigious, comprehensive cancer centers based in the US, covering how these centers started their programs, what they are currently doing, and recommendations for starting integrative medicine clinics. The book also discusses the potential harm of alternative and complementary medicine, legal issues, and how to communicate with patients.

Nuclear receptors are ligand activated transcription factors that control numerous biological functions. Consequently, altering activity of these receptors is proposed, and indeed documented, to affect many physiological and pathological conditions in experimental animals and humans. Thus, nuclear receptors have become a major target in the effort to treat numerous diseases.This book will shed light on and emphasize intricate processes involved in designing as well as discovering physiological and pharmacological modulators of these important proteins. World-renowned scientists will share with the reader their professional expertise and extensive experience acquired through decades working with nuclear receptors. Chapters address the various means and consequences of modulating nuclear receptor activity will be presented and discussed. These modulators cover a wide span of moieties ranging from synthetic chemicals to natural products. In addition, the classification of these chemicals ranges from pan agonists to selective agonists and inverse agonists to antagonists. They also include proteolytic means to obliterate the receptor in the event that modulating its activity through canonical pharmacological agents becomes less effective and/or less desirable due to anticipated or experienced toxicities. Modulation of receptor activity may also take place in the absence of a ligand or through manipulating the structure of the receptor itself by controlling posttranslational events.

Based on the most novel approaches and cutting-edge clinical and scientific information regarding radionuclide imaging and therapies for neuroendocrine tumors, this clinical guidebook represents a unique collaborative effort between endocrinologists, nuclear physicians, oncologists, surgeons, physicists, radio-pharmacists and geneticists. It begins with the embryology, classification and molecular genetics of gastroenteropancreatic neuroendocrine tumors and carcinoids, chromaffin cell tumors, and MEN1- and MEN2-related tumors. Following a chapter on radiopharmaceuticals in neuroendocrine imaging, it turns to the physics and technology of current and cutting-edge radiology, including SPECT/CT and PET/CT and PET/MR. Discussing of radionuclide imaging covers the tumors mentioned above, as well as pulmonary and thymic neuroendocrine tumors and medullary thyroid carcinoma. A presentation of radionuclide therapies follows, including 131I-MIBG therapy, somatostatin receptor-based therapy, and alpha radionuclide therapy, as well as the role of nanoparticles. Comprehensive and up-to-date, Diagnostic and Therapeutic Nuclear Medicine for Neuroendocrine Tumors will assist and guide physicians who encounter patients with these conditions, either from a diagnostic or therapeutic standpoint, and particularly emphasizes the current and emerging medical devices and imaging and therapeutic options.

In recent decades, cytopathology has assumed an increasing role in the primary diagnosis of mass lesions owing to its ability to deliver rapid, non-invasive, and timely information. This book provides a comprehensive overview of the role of cytology at various body sites. The diagnostic details covered are abbreviated in comparison with those in pathology texts. Instead, a more clinical approach is taken, with the focus on the advantages and limitations of techniques and the key features of entities that are important to clinicians. Pathological-clinical correlation is highlighted throughout the book, ensuring that it will be highly relevant for clinicians. In particular, physicians who deal with oncology patients will find it to be a rich source of guidance on how to use and understand cytopathology in the diagnosis and exclusion of malignancy.

¿Drs. Franco and Rohan bring together a timely and comprehensive set of reviews describing the biologic basis of carcinogenesis, issues related to measurement and interpretation of cancer precursors, site specific precancerous conditions, and control of cancer precursors ¿The book has several important strengths, most notably the wealth of current information on cancer precursors and related topics provided by an impressive cast of cancer researchers. ¿ it effectively provides specific and compelling reasons for studying cancer precursors, the most up-to-date and comprehensive collection of reviews on the topic, and a realistic picture of the complexities facing research of cancer precursors.¿ ¿American Journal of Epidemiology "In this book, Drs. Franco and Rohan have succeeded in preparing a comprehensive, timely, and critical review of the substantial progress that has been made in our understanding of cancer precursors. They have enlisted experts in the field who have contributed authoritative chapters to a wide variety of cancers with emphasis on the etiology and natural history, including the role of environmental and heritable factor that provoke normal cells to undergo malignant transformation. Epidemiologic data are linked whenever possible to molecular as well as clasical cellular pathology, providing a fuller understanding of the casual events and mechanisms that initiate the carcinogenic process." -From the Foreward by Joseph F. Fraumeni, Jr., M.D., M.S. Director, Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville, MD This book provides an overview of the progress made in the last few years on the epidemiology, detection methods, and preventive stategies for cancer precursors. Contributors to the 25 chapters are among the world's most knowledgeable scientists in the areas of molecular pathology, epidemiology, and control of cancer precursors. Their reviews of the topic are accessible to a large professional base that includes basic cancer researchers, clinical oncologists, pathologists, molecular biologists, epidemiologists, nurses, health professionals working on policy implications, and graduate students in cancer-related fields. Divided into five sections, the book begins with brief overviews of the molecular basis of carcinogenesis and of the histological aspects of cancer precursors. Issues related to the measurement, interpretation, and the study of precursor lesions are addressed in Part II, including timely chapters on epidemiologic approaches to studying intermediate endpoints, the impact of measurement error, and methods of processing biological specimens for molecular epidemiology studies. The main section of the text is found in Part III, with chapters on cancer precursors at the most important anatomical sites at which solid tumors occur, including the lung, breast, colon, esophagus, and prostate. The site-specific reviews include discussions of the epidemiology of those lesions, and, where appropriate, aspects of their detection and prevention. The final sections of the book feature valuable overviews on screening and prevention strategies and the role of evidence-based medicine in judging the value of such strategies for national and international policy guidelines on cancer control.

Antifolates are an important class of anticancer drugs originally developed as anti leu- kemic agents, but now used, usually in combination with other drugs, for the treatment of a wide range of tumors, notably carcinomas of the head and neck, breast, germ cell tumors, non-Hodgkin's lymphoma, acute lymphoblastic leukemia, and osteogenic sar- comas. 5-Fluorouracil and its prodrugs also target, in part, the folate-dependent enzyme, thymidylate synthase. Furthermore, folate supplementation in the form of leucovorin, modulates 5-fluororuacil activity. 5-Fluorouracil is widely used in the treatment of colorectal and gastric cancer and in combination for other solid tumors such as breast and head and neck cancers. Ongoing clinical trials with the newer antifolates suggest that the range of solid tumors where these agents will be of use may broaden further. Half a century ago, interesting scientific and clinical discoveries suggested that folie acid was a vitamin involved in vital cellular metabolic processes. The folate analogs, aminopterin and methotrexate, were synthesized by the American Cyanamid Company in an attempt to interfere with these processes and were shown to have anticancer activity by Farber and his colleagues. Hence, the principle of antimetabolite therapy for the treatment of cancer was established. Biomedical research over the following years led to a deeper understanding of the complex biochemical pharmacology of folates and antifolates. Selective antimicrobial agents were discovered, but more tumor-selective anticancer agents did not immediately emerge.

Protein kinase CK2 (formerly casein kinase II or 2) is known to play a critical role in the control of cell growth and cell death and is thus intimately involved in the development of cancer. More specifically, CK2 has been found to be elevated in all cancers examined. While CK2 levels are known to be high in proliferating normal cells, CK2 has also been found to be a potent suppressor of apoptosis and is a link to the cancer cell phenotype, which is characterized by deregulation of both cell proliferation and cell death. Indeed, it would appear that CK2 impacts many of the hallmarks of cancer and it has now gained considerable attention as a potential target for cancer therapy. Protein Kinase CK2 and Cellular Function in Normal and Disease States increases knowledge of the role of CK2 in the development of cellular dysfunction and emphasizes that this protein may serve as a target of drug development for improved cancer therapy. In addition, it is a handy tool that provides cancer researchers, graduate students, and all scientists involved in CK2 research with one main source for the latest advances in CK2 research.

The possibility of treating cancer, a disease frequently defined by
genetic defects, by introducing genes that target these very
alterations has generated tremendous enthusiasm. This enthusiasm,
however, has been tempered by an increasing number of obstacles to
successful therapy, including vector systems that do not reach systemic
metastases, therapeutic genes with redundant mechanisms allowing for
cellular resistance, and toxicities in clinical trials that result in
premature closure. The three comprehensive sections of this volume
present currently available cancer gene therapy techniques, with
specific attention to these trouble spots. Part I describes the various
aspects of gene delivery including vehicles, or vectors, and their
respective characteristics and production methods. In Part II, the
contributors discuss strategies and targets for the treatment of
cancer, including methods for cell-death therapies, correction of
underlying genetic defects at the molecular level, and activation of
the immune system or tumor microenvironment. The contributors provide a
succinct framework for understanding the basic underlying oncogenic
changes, which encourages the development of vectors engineered to
exploit these gene mutations through selective spread of the vector in
tumor cells with the specific changes. Finally, in Part III, experts in
clinical gene therapy trials discuss the difficulties inherent in
bringing gene therapy treatment for cancer to the clinic, and principal
investigators present gene therapy approaches in the clinical testing
stage and the results that have reached the stage ofclinical
testing.of these trials.

This volume comprehensively covers the multiplicity and diversity of mechanisms underlying patient resistance to currently approved anti-cancer drugs, including tyrosine kinase inhibitors and monoclonal antibodies, blockers of growth factor receptors and their downstream pathways, which play essential functions in cancer progression. Each chapter will cover a specific group of targets and the cognate drugs, along with molecular modes of innate and evolving resistance.

This text is the only book of its kind to provide specific guidance applicable to limited resource settings and builds up from the foundation of general practitioner or general pediatrician competence. Written and edited by leaders in the field, this manual educates physicians on the essential components of the discipline, filtered through the experience of specialists from developing countries, with immediate applicability in the specific healthcare environment in these countries. Typically, manuals of pediatric hematology-oncology are written by specialists from high-income countries, and usually target an audience with a sub-specialist level of training, often assisted by cutting-edge diagnostic and treatment facilities. However, approximately 80% of new cases of cancer in children appear in mid- and low-income countries. Almost invariably, general practitioners or general pediatricians without special training in oncology will look after children with malignancies who enter the health care system in these countries. The diagnostic facilities are usually limited, as are the treatment options. The survival figures in these conditions are somewhere below 20%, while in high-income countries they are in the range of 80% for many childhood cancers. This book includes simplified therapy protocols, pain therapy and palliation, as well as ward procedures such as bone marrow aspiration/biopsies, intravenous therapy and chemotherapy drugs mixing. It provides an overview of pediatric cancer epidemiology, cancer registration and organizing support networks and features the management of cancers with associated pathology like AIDS, malnutrition, malaria and tuberculosis.

This book contains most updated information on synthesis of magnetic nanohybrids, their physio-chemical properties, and key biological applications. It highlights the complexity of nanoheterostructures, especially magnetic metal oxides, ferrites and doped magnetic nanomaterials, and discusses their potential applications in the early detection, imaging and treatment of cancer. It also covers the toxicity and risk assessment of multifunctional nanomaterials. Providing an overview of magnetic nanoheterostructures, it appeals to a wide audience, from beginners and graduate-level students to experts in academia and industry.

With the coming of the new millennium we are witnessing a revolution in our understanding of cancer genetics. These are very exciting times. Today we have at our disposal the technology to diagnose abnormalities in our cancer genes and the means to correct the deficit and very soon we will have the complete sequence of the human genome. With the use of gene chip technology the way doctors will be able to assess patients will change completely. Today we can diagnose abnormalities in ten thousand genes and within a short period of time we will be able to screen through our genome and discover potential abnormalities in our proto-oncogenes, tumour suppressor genes, differentiating genes, apoptotic genes and pro-inflammatory genes. In this book various authors have highlighted specific genes that could be expressed, overexpressed, neutralised or h- nessed to achieve cancer control. The problem of transferring the therapeutic gene into the cancer cell has been partly addressed with major developments in the field of naked plasmid DNA, adenovirus, retrovirus and adeno-associated viruses. However, further improvements are yet to be made to achieve significant gene transfer. Gene expression, in particular specificity of gene transfer, is obviously an important issue and one which is highlighted in this book by the use of specific promoter.

The aim of this book will be to contribute to the education of a new generation of experts in urology, molecular biology, pathology and oncology, offering them sufficient knowledge in basic and translational research to be fluency in the web of interacting networks playing a role in prostate cancer development, progression, metastasis and drug-resistance.The volume will cover the latest innovative researches in prostate cancer, with particular emphasis to the state-of-the-art analysis technologies that are essential for the accurate identification of molecular targets for disease diagnosis, molecular mechanisms of tumorigenesis, markers for susceptibility, molecular-based prognostic prevision, characterization of biomarkers of drug efficacy and drug resistance, validation of new therapeutics and diagnostics. Current advancements on the intersecting data concerning transcriptomes, proteomes, the molecular techniques referred as "omes," will be reported and discussed.

This volume details standard techniques for the characterization of urothelial carcinoma as well as methods to investigate mechanisms of carcinogenesis. Chapters guide readers on cellular and animal models for urothelial carcinoma and related diseases, molecular analyses from body fluids, and new approaches to therapy. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Urothelial Carcinoma: Methods and Protocols hopes that the techniques described in this volume will contribute to the current upturn in research on urothelial carcinoma and to the application of its results in clinical practice.

This volume, Biological and Hormonal Therapies of Cancer, which is part of the series Cancer Treatment and Research, presents selected new information concerning biologic and hormonal therapy of cancer. We have attempted to provide the reader with topics of major interest in a timely fashion. There is renewed interest in biologic therapy of cancer. Two chapters review the role of interferon in the hematologic malignancies and in solid tumors. Vaccine therapies have come to the forefront of cancer therapy re cently, and two chapters approach different strategies of vaccine therapies; one reviews the cellular vaccine therapies and another the anti-idiotype ap proach. The hormonal therapy chapters focus on current uses of endocrine therapy in endometrial, breast, and prostate cancer. In addition, hormonal strategies for the prevention of breast cancer and endometrial cancer, including excit ing information relating to phytochemicals, are presented. The effects of tamoxifen on endometrium is a topic of major interest and is discussed in detail. Finally, there is a chapter on estrogen receptor expression and regula tion in human breast cancer. These chapters are all written by experts in the field and contain timely and relevant information of interest to laboratory and clinical scientists and practitioners alike. Biologic and endocrine therapies represent major areas of cancer research interest. The advent of newer biologic therapies, including new antibody targeted treatments, and the use of biologics as tumor modulators to enhance the effects of other treatment regimens is an exploding avenue of research."

Antibody-directed enzyme prodrug therapy (ADEPT) directly addresses the major problem in cancer chemotherapy-its lack of selectivity. Antibody delivery combined with the amplification provided by the enzymatic activation of prodrugs enables selection to be made between tumour and normal tissue. ADEPT offers a novel field of opportunities in the therapy of systemic cancer and may be a major advance for the treatment of solid tumours. This book is the first to describe ADEPT in detail. Each chapter reviews an aspect of the immunology, enzymology, biochemistry, chemistry, and cancer chemotherapy which have been integrated into the ADEPT concept. An additional chapter describes the related approach of gene-directed enzyme prodrug therapy (GDEPT). This latter approach is still in its infancy but ADEPT has entered the clinic. The initial clinical studies with ADEPT are included and discussed in detail.

Diverse molecular, cellular, and environmental events must all come together to allow the successful formation of secondary cancers, metastases. The second edition of Metastasis Research Protocols, brings together the most up to date versions of the seminal techniques that were presented in the first edition and also includes new techniques that have recently been shown to be important in illuminating the processes underlying this important area of biology. Presented by top scientists, the collection includes a wide spectrum of articles encompassing important key methods and to introduce new methods which are making an impact in the area of metastasis research. Volume 1 includes key cellular and molecular techniques relevant to the exploration of cancer cells and tissues, the focus is on the tools that have been shown to be helpful in unravelling the molecular processes important in cancer metastasis. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Metastasis Research Protocols, Second Edition seeks to aid scientists in the further study of new methods in the area of metastasis research.

This volume represents a collection of contributions from the 6th International Conference on Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Related Diseases held in Boston from September 12-15, 1999. The mission of this meeting was to bring together senior and junior investigators to both announce and examine their recent advancements in cutting-edge research on the roles and actions of lipid mediators and their impact in human physiology and disease pathogenesis. The meeting focused on new concepts in these areas of interest to both clinicians and researchers. The program included several outstanding plenary lectures and presentations by leading experts in the fields of cancer and inflammation. In addition, the Boston meeting presented three Young Investigator awards, one in each of the major focus areas. The meeting was exciting and proved to be very memorable. The program was developed with an emphasis on recent advances in molecular and of lipid mediators relevant in cellular mechanisims involved in the formation and actions inflammation and cancer. Plenary lectures were presented by Prof. Bengt Sammuelsson (Karolinska Institute, Stockholm; 1982 Nobel Laureate in Physiology or Medicine) and Prof. E. 1. Corey (Harvard University; 1990 Nobel Laureate in Chemistry). Both of these plenary lectures were held on Day 1, which set an exciting tone for this meeting. Immediately following these plenary lectures, three simultaneous breakout sessions were held, one of inflammation, a second on cancer and synthesis of novel inhibitors, and a third on enzymes-lipoxygenases/cyclooxygenases and inhibitors.

This timely desk reference focuses on marine-derived bioactive substances which have biological, medical and industrial applications. The medicinal value of these marine natural products are assessed and discussed. Their function as a new and important resource in novel, anticancer drug discovery research is also presented in international contributions from several research groups. For example, the potential role of Spongistatin, Apratoxin A, Eribulin mesylate, phlorotannins, fucoidan, as anticancer agents is explained. The mechanism of action of bioactive compounds present in marine algae, bacteria, fungus, sponges, seaweeds and other marine animals and plants are illustrated via several mechanisms. In addition, this handbook lists various compounds that are active candidates in chemoprevention and their target actions. The handbook also places into context the demand for anticancer nutraceuticals and their use as potential anti-cancer pharmaceuticals and medicines. This study of advanced and future types of natural compounds from marine sources is written to facilitate the understanding of Biotechnology and its application to marine natural product drug discovery research.

Opening Speech; E.D. Hondros. Welcome Address; H.H. van der Kroonenberg. Safety and Efficacy in Boron Neutron Capture Therapy; D. Gabel. Some Aspects of BNCT at the Brookhaven National Laboratory; D.D. Joel, et al. INEL BNCT Program Directions with Respect to Clinical Trials of BNCT; R.V. Dorn III. The Department of Energy Research Program in Boron Neutron Capture Therapy; R.W. Wood, D.W. Cole Jr. Current Overview on the Approach of Clinical Trials at Petten; R.L. Moss. Review of the Physics Calculations Performed for the BNCT Facility at the HFR Petten; P. Watkins, et al. From Filter Installation to Beam Characterization; F. Stecher-Rasmussen, et al. Neutron Spectrometry Measurements of the Petten HFR, HB11 Neutron Beam; C.A. Perks, H.J. Delafield. A Semi-Empirical Method of Treatment Planning for Boron Neutron Capture Therapy; C.P.J. Raaijmakers, et al. Present Status of the Three-Dimensional Treatment Planning Methodologies for the Petten BNCT Facility; P. Watkins. A Phase 1 Biodistribution study of p-Boronophenylalanine; J.A. Coderre. RBE in Normal Tissue Studies; R.A. Gahbauer, et al. Treatment planning and optimization for Pion Therapy; H. Blattmann. Dose Calculations Based on Images Reconstructions; F.J. Wheeler, D.E. Wessol. Borocaptate Sodium (BSH) Pharmacokinetics in Glioma Patients; H. Fankhauser, et al. BSH in Patiens with Malignant Glioma: Distribution in Tissue, Comparison between BSH Concentration and Histology; D. Haritz, et al. Macroscopic and Microscopic Biodistribution of BSH in a Rat Glioma Model; C.P. Ceberg, et al. Healthy Tissue Tolerance Studies for BNCT at the High Flux Reactor in Petten-First Results; A. Siefert. Cellular Pharmacokinetics of BNCT Compounds and their Cellular Localization with EELS/ESI; R. Verrijk, et al. Large Animal Model Studies of Normal Tissue Tolerance using an Epithermal Neutron Beam and Borocaptate Sodium; P.R. Gavin, et al. Proposal for Patient Selection Criteria and Follow-up for BNCT in Patients with Supratentorial Malignant Gliomas; H. Fankhauser, G. Stragliotto. A Proposal for Phase 1 Clinical Trials of Glioma Patients; H. Bartelink. Approaches to the Design and Evaluation of Compound for BNCT; A.H. Soloway, et al. The implementation Strategy for BNCT Trials in Australia; B.J. Allen. Author Index. Participants. Subject Index. [End of file]

TLR4 is one of the most important innate immunity receptors, its function mainly consisting in the activation of inflammatory pathways in response to stimulation by Pathogen-Associated Molecular Patterns (PAMPs) and Damage Associated Molecular Pattern molecules (DAMPs). This volume critically reviews the different types of TLR4 activators and inhibitors, discusses the role of molecular aggregates in agonism/antagonism as well as the pivotal role of the CD14 receptor in the modulation of TLR4 signal and the molecular details and actors of the intracellular cascade. The book presents the role of TLR4 in several pathologies, such as sepsis and septic shock caused by receptor activation by gram-negative bacterial lipopolysaccharide (LPS), in neurodegenerative and neurological diseases such as Parkinson and Alzheimer's diseases, and Amyotrophic Lateral Sclerosis (ALS). It reviews the role of TLR4 in neural stem cell-mediated neurogenesis and neuroinflammation and in Human Induced Pluripotent Stem Cells and Cerebral Organoids and discusses the emerging role of micro-RNA (miRNA) regulation by TLR4.

My training started in 1971, when I joined the First Department of Medicine of Chiba University, as Dr. Kunio Okuda became chair ofthe department. To acquire training ingeneralpathology, Iapplied for the Intern MatchingProgram and started as aninternin the DepartmentofPathologyofYale University, in 1973.While Iwas achiefresident, Ispent 10months in Dr. GeraldKlatskin'sofficestudyingthe com plete set of his famous liver biopsy samples (the Klatskin Collection). In 1976, I movedtoJohnWesleyHospital, where therewasagroup from the USC (University ofSouthern California) Liver Unit, to obtain further pathology training under the guidanceofDr. Robert L. Peters. Those experiences have given me ample opportu nity to see the differences between the United States and Japan. Ofcourse, 28 years ago in downtown Los Angeles there were enormous num bers ofpatients suffering from typical alcoholic liver diseases. Now in Japan, in contrast, we have an enormous number ofpatients suffering from hepatocellular carcinoma (HCC), due in particular to hepatitis C viral infection. Last year, in the DepartmentofGastroenterology at the University ofTokyo, we had approximately 500 admissions due to HCC. Thus, we have an urgent need to prevent the develop ment ofHCC and to provide better treatment for such patients through a basic un derstanding ofvirology, clinical features, and treatment modalities. The first single-topic conference on "TherapyofViral Hepatitis and Prevention ofHepatocellular Carcinoma" was organized by the Japan Society ofHepatology (Kiwamu Okita, Director General) and was held November 14-15,2002, near Mt. Fuji. Thisbook, which is asummaryofthe meeting, helps toupdate relevantinforma tion on this vital topic. June 28, 2003 Masao Ornata, M.D."