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Advances in Cancer Research, Volume 150, the latest release in this ongoing series, covers the relationship(s) between autophagy and senescence, how they are defined, and the influence of these cellular responses on tumor dormancy and disease recurrence. Specific sections in this new release include Autophagy and senescence, converging roles in pathophysiology, Cellular senescence and tumor promotion: role of the unfolded protein response, autophagy and senescence in cancer stem cells, Targeting the stress support network regulated by autophagy and senescence for cancer treatment, Autophagy and PTEN in DNA damage-induced senescence, mTOR as a senescence manipulation target: A forked road, and more. - Addresses the relationship between autophagy and senescence in cancer therapy - Covers autophagy and senescence in tumor dormancy - Explores autophagy and senescence in disease recurrence

This book deals with the paradoxical role of autophagy in tumor suppression and tumor promotion in cancer cells. Autophagy plays opposing, context-dependent roles in tumors; accordingly, strategies based on inhibiting or stimulating autophagy could offer as potential cancer therapies. The book elucidates the physiological role of autophagy in modulating cancer metastasis, which is the primary cause of cancer-associated mortality. Further, it reviews its role in the differentiation, development, and activation of multiple immune cells, and its potential applications in tumor immunotherapy. In addition, it examines the effect of epigenetic modifications of autophagy-associated genes in regulating tumor growth and therapeutic response and summarizes autophagy's role in the development of resistance to a variety of anti-cancer drugs in cancer cells. In closing, it assesses autophagy as a potential therapeutic target for cancer treatment. Given its scope, the book offers avaluable asset for all oncologists and researchers who wish to understand the potential role of autophagy in tumor biology.

Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging: Volume 9: Human Diseases and Autophagosome offers a valuable guide to both cellular processes while helping researchers explore their potentially important connections. Volume 9 emphasizes the role of autophagy in diseases, such as leukemia, antifungal and antibacterial immunity, and transplantation. This volume also explains, in detail, the molecular mechanism(s) underlying the formation of autophagosomes, including the progression of omegasomes to autophagosomes. This information is important because one of the major functions of autophagy is to degrade and eliminate excessive, old, and harmful materials from the cell. Autophagosomes receive these materials (cellular cargo) and transport them to lysosomes for degradation. Lysosomes contain the digestive enzymes (hydrolases) that breakdown proteins, lipids, carbohydrates, etc. (self-digestion). To further explain this phenomenon, the role of the endoplasmic reticulum (ER) in the formation of autophagosomes is discussed. ULK1 and Beclin 1 proteins are also important in the initial formation of autophagosomes, and are also discussed. Because much of the early research in this area was carried out using yeast cells, the role of Golgi complex in the autophagosome formation in these cells is explained. This volume also includes an explanation of the role of the autophagy-related gene ATG5 in cancer (e.g., gastrointestinal cancer). Paradoxically, autophagy is a'double-edged sword because it eliminates some pathogens, whereas it can be used by some intracellular pathogens to multiply and cause infection. This book is an asset to newcomers, providing a concise overview of the role of autophagy in necrosis and inflammation, while also serving as an excellent reference for more experienced scientists and clinicians. - Presents the most advanced information regarding the role of the autophagic system in life and death - emphasizes autophagy in diseases, such as leukemia - Introduces new, more effective therapeutic strategies in the development of targeted drugs and programmed cell death, providing information that will aid in preventing detrimental inflammation - States recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities - Edited work with chapters authored by leaders in the field from around the globe—the broadest, most expert coverage available

This textbook presents concise chapters written by internationally respected experts on various important aspects of cancer-associated metabolism, offering a comprehensive overview of the central features of this exciting research field. The discovery that tumor cells display characteristic alterations of metabolic pathways has significantly changed our understanding of cancer: while the first description of tumor-specific changes in cellular energetics was published more than 90 years ago, the causal significance of this observation for the pathogenesis of cancer was only discovered in the post-genome era. The first 10 years of the twenty-first century were characterized by rapid advances in our grasp of the functional role of cancer-specific metabolism as well as the underlying molecular pathways. Various unanticipated interrelations between metabolic alterations and cancer-driving pathways were identified and currently await translation into diagnostic and therapeutic applications.Yet the speed, quantity, and complexity of these new discoveries make it difficult for researchers to keep up to date with the latest developments, an issue this book helps to remedy.

Autophagy principally serves an adaptive function to protect organisms against diverse human pathologies, including cancer and neurodegeneration. Recent developments using in vitro, ex vivo and in vivo models show the involvement of the autophagy pathway in immunity and inflammation. Moreover, direct interactions between autophagy proteins and immune signalling molecules have also been demonstrated. Defects in autophagy - similar to cancer, neurodegenerative diseases and aging - through autophagy gene mutation and/or microbial antagonism, may underlie the pathogenesis of many infectious diseases and inflammatory syndromes. In spite of the increasing awareness of the importance of autophagy in these pathophysiological conditions, this process remains underestimated and is often overlooked. As a consequence, its role in the initiation, stability, maintenance, and progression of these diseases are still poorly understood. This book reviews the recent advances regarding the functions ofthe autophagy pathway and autophagy proteins in immunity and inflammation, focusing on their role in self-nonself distinction, their implications in innate and adaptive immune responses and their dysregulation in the pathology of certain inflammatory and autoimmune diseases.

Lessons in Immunity: From Single-cell Organisms to Mammals stems from the activity of the Italian Association of Developmental and Comparative Immunobiology (IADCI), represented by the editors. This book is presented as a series of short overviews that report on the current state of various relevant fields of immunobiology from an evolutionary perspective. The overviews are written by authors directly involved in the research, and most are members of the IADCI or have otherwise been involved in the related research for their respective overview. This publication offers scientists and teachers an easy and updated reference tool. - Provides simple and updated reviews on the immunobiology of a wide spectrum of organisms, considered in an evolutionary context - Focuses on both cells and humoral components of a variety of non-classical model organisms - Offers in a single volume many contributions which can help with understanding the evolution of immune responses and the main adaptations in animal phyla - Presents a valuable holistic cross-sectional approach for teaching immunology and its applications

The fifth Annual Pezcoller Symposium entitled, Apoptosis, was held in Trento, Italy, June 9-1I, 1993 and was focused on the specific phenomena leading to Programmed Cell Death (PCD) or Apoptosis, and the mechanisms involved. With presentations at the cutting edge of progress and stimulating discussions, this Symposium addressed the genetics and molecular mechanisms determining PCD and the role of this suicidal process in cancer and the immune system. The functions of pS3, c myc and bel 2 in affecting apoptosis in different cell types and the role of ions and intracellular pH changes and that of intranuelear endonueleases are given particular emphasis as are the effects of anticancer agents, hormone imbalances and growth factors. The role of pS3, a tumor suppressor gene, in inducing PCD is discussed in detail as pertinent to hematological and non-hernatological tumors. The requirement of pS3 for the induction ofapoptosis by ionizing radiation or adenovirus oncoproteins is outlined. Decision points during the cell cyele affecting the cascade ofevents leading to PCD are discussed as is their role as'switches'under the control of c-myc and bel-2 proteins or the influence of cyele specific drugs. The concurrent requirement of multiple signals in determining apoptosis is emphasized. The examples of the role of PCD in the regulation of hematopoiesis, and in the generation of antigen-specific immune repertoire are illustrated.

The fifth of the annual research conferences of the American Institute for Cancer Research was held September l-2, 1994, at the L'Enfant Plaza Hotel in Washington, DC. Appropriately, in view of current directions in research, the theme was'Diet and Cancer: Molecular Mechanisms of Interactions'. This proceedings volume contains chapters from the platform presentations and abstracts from the poster session held on the end of the first day. The subtopics for the tl;rree sessions held were'Retinoids, Vitamins A and Din Cancer Prevention and Therapy,''Choline and Lipids: Signal Transduction, Gene Expression and Growth Regulation,'and'Dietary Factors and Regulation of Oncogenes, Growth and Differentiation.'A general overview on vitamins A and D emphasized that A and D, in addition to their established roles in vision, reproduction, and bone mineral homeostasis, may play significant roles in regulating cell function. Vitamin A metabolites, trans-retinoic acid and 9-cis-retinoic acid, regulate growth and differentiation. Furthermore, vitamin A­ deprived animals were more susceptible to both spontaneous and carcinogen-induced tumors. Epidemiological studies showed a correlation between low A intake and higher incidences of certain types of human cancers. Conversely, all-trans retinoic acid is useful in treatment and control of certain types of cancer. Physiologically, Vitamin D is converted to the active form, l,25-dihydroxyvitamin D (VD). VD regulates hormone production and secretion, myocardial contractility, vascu­ 3 3 3 lar tone, and growth inhibition and differentiation.

Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and forward thinking, these books offer a valuable guide to both cellular processes while inciting researchers to explore their potentially important connections. Considering that autophagy is associated with numerous biological processes, including cellular development and differentiation, cancer (both antitumor and protumor functions), immunity, infectious diseases, inflammation, maintenance of homeostasis, response to cellular stress, and degenerative diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and prion diseases, there is a great need to understanding its role. Cell homeostasis is achieved by balancing biosynthesis and cellular turnover. In spite of the increasing importance of autophagy in various pathophysiological situations (conditions) mentioned above, this process remains underestimated and overlooked. As a consequence, its role in the initiation, stability, maintenance, and progression of these and other diseases (e.g., autoimmune disease) remains poorly understood. Volumes in the Series

The book provides a comprehensive overview to understanding the integrated impact of the concepts of cellular and molecular aspects, models, environmental factors, and lifestyle involved in premature aging. Additionally, it examines how functional food, dietary nutraceuticals or pharmacological compounds can reverse inflammation and premature aging based on personalized medicine. This book is a valuable resource for health professionals, scientists and researchers, nutritionists, health practitioners, students and for all those who wish to broaden their knowledge in the allied field. - Includes models of aging, including worm, mouse and human - Explores the relationship of inflammation with diseases, including ocular health, Alzheimer's and Parkinson's disease, and muscle health - Encompasses a variety of lifestyle impacts, including diet, exercise and nutrition - Includes suggested nutritional interventions

Rejection and Tolerance is the latest subject in the Continuing Education series, organized by Fondation Marcel Mérieux and Université Claude Bernard in Lyon. The annual subject is chosen to reflect the status of the topical issues of the year, as taught by leading international experts. The contribution of transplantation and clinical immunology to advanced medicine is considerable and promising. The annual volumes in this series keep the reader abreast of these developments.

Der erste Band der neuen Reihe gibt einen weitgefächerten Überblick über die Probleme, Grenzen und Möglichkeiten, Tierversuche in der biomedizinischen Forschung zu reduzieren. Behandelt werden die gesetzlichen Grundlagen in den deutschsprachigen Ländern, Toxikologie und In-Vitro-Toxikologie, In-Vitro-Systeme in Pharmakologie und Physiologie, Immunologie, Molecular Modelling, Videomikroskopie, In-Vitro-Systeme in der Krebsforschung und in der Ökotoxikologie. Experten aus Industrie, Universität und Behörden versuchen, bisher Geleistetes darzustellen, Schwachstellen aufzuzeigen und zukunftsträchtige Problemlösungsmodelle vorzustellen.

Apoptosis plays a central role in the regulation of cell proliferation. Disruption of this control mechanism may cause serious human diseases such as encephalomyelitis and cancer. Thus, understanding of the molecular mechanisms of apoptotic cell death should lead to fundamental advances in the therapy of these diseases.

The volume contains the main papers presented at the 1994 EUROTOX Congress, Basel, Switzerland, August 21-24, 1994. Toxicology has become a less descriptive science because more importance has been placed on the mechanisms underlying toxic effects. This is reflected in symposia and workshops devoted to species differences in organ toxicity, receptor-mediated toxicity and stereochemical effects of xenobiotics. Recent progress in the fields of immunotoxicology, ecotoxicology, and neurotoxicology is highlighted and documented together with the present discussion on harmonized regulatory guidelines.

Renal transport and xenobiotic metabolism play an important role in the detoxication and excretion of potentially toxic xenobiotics. However, recent experimental evidence has demonstrated that renal xenobiotic metabolism and renal transport processes also play an important role in the nephrotoxicity of xenobiotics and xenobiotic metabolites. The high blood flow to the kidney combined with its ability to concentrate solutes may expose the kidney to high concentrations of xenobiotics and xenobiotics metabolites present in the systemic circulation. Recently, it has been demonstrated that xenobiotic metabolites formed in the liver and other organs may be targeted to the kidney by selective transport systems~ many xenobiotics require enzymatic transformation to proximate reactive metabolites to elicit their toxic and carcinogenic effects. The enzymatic formation of reactive metabolites is termed bioactivation. The bioactivation mechanisms for many nephrotoxicants have, at least in part, been elucidated in the past 15 years. Many ultimate toxicants formed in the kidney are electrophiles whose interaction with cellular macromolecules may cause a perturbation of normal cell function resulting in necrosis and/or cancer (Anders 1988). Electrophilic metabolites may bind to nucleophilic sites in cellular macromolecules~ the importance of covalent modification of protein and DNA in cell killing and in the induction of tumors is established (Miller and Miller 1981~ Nelson and Pearson 1990~ Hinson and Roberts 1992). The objective of this review is to summarize new information about renal transport, renal bioactivation and their relation to nephrotoxicity using two relevant example for the basic mechanisms outlined above.

Ultraviolet radiation, a component of sunlight, has been recognized by photobiologists, dermatologists, and oculists as a potential hazard for human health because of its genotoxic, carcinogenic and immunotoxic properties. Its effects on human health include the induction of skin cancers, ocular damage and impairment of immunity to certain infections. A few decennia ago it was demonstrated that UV photons can affect the activity of the immune system through interactions with the skin. This means that UV not only changes normal cells into cancer cells but also permits the outgrowth of the UV -transformed cells by depressing the immune system. An intriguing question is what interactions between UV radiation and the skin initiates alterations in immune function in the exposed skin and systemically, i. e. in other places than the exposed skin. During the last 20 years many studies have been performed in order to investigate the immunosuppressive activities of UVB in laboratory animals and in human volunteers. In particular effects of UVB radiation on resistance to tumours and skin associated infections have been examined. In addition, effects of UVB radiation on immune parameters such as contact hypersensitivity and delayed-type hypersensitivity (both type IV hypersensitivity reactions), mixed lymphocyte reactions, mixed skin lymphocyte reactions, antigen presentation and numbers and function of Langerhans cells have been studied intensively. The antigenicity of murine tumours which are caused by UVB radiation was one of the first items to be investigated (Kripke, 1974).

The Endoplasmic Reticulum (ER) is an organelle with extraordinary signaling and homeostatic functions. It is the organelle responsible for protein folding, maturation, quality control and trafficking of proteins destined for the plasma membrane or for secretion into the extracellular environment. Failure, overloading or malfunctioning of any of the signaling or quality control mechanisms occurring in the ER may provoke a stress condition known as ‘ER stress'. Accumulating evidence indicates that ER stress may dramatically perturb interactions between the cell and its environment, and contribute to the development of human diseases, ranging from metabolic diseases and cancer to neurodegenerative diseases, or impact therapeutic outcome. This book primarily focuses on the pathophysiology of ER stress. It introduces the molecular bases of ER stress, the emerging relevance of the ER-mitochondria cross-talk, the signaling pathways engaged and cellular responses to ER stress, including the adaptive Unfolded Protein Response (UPR), autophagy as well as cell death. Next the book addresses the role of ER stress in physiology and in the etiology of relevant pathological conditions, like carcinogenesis and inflammation, neurodegeneration and metabolic disease. The last chapter describes how ER stress pathways can be targeted for therapeutic benefit. Altogether, this book will provide the reader with an exhaustive view of ER stress biology and the latest insights in the role of ER stress in relevant human diseases.

Apoptosis is a fascinating concept for the basic scientist. This is not only because of the multifaceted variety of proposed and discovered mechanisms, but because apoptosis represents a fundamental pathway for cell renewal. The study of apoptosis has resulted in an array of discoveries on signal transduc­ tion and downstream effects that have facilitated and advanced many fields in biology, including research on cancer and other diseases. Thus, the apoptotic process can be viewed as the largest effort of the scientific community to understand how cells work and tissues assemble or remodel. The most direct consequence of this accumulated knowledge is a greater understanding of disease and pathological mechanisms. The end result of these efforts will be significant contributions to health and the adoption of new, never anticipated, therapeutic approaches. This book represents the summation of considerable effort from a significant group of contributors from all over the world as well as from its editors. In this fashion, many viewpoints have been collected and SUbjected to thorough academic discussion. The concepts contained in this medically important volume will stimulate and renew the ideas of scientists and indeed, will generate additional work to advance biological knowledge even further. The emphasis of this volume cements what has been established, adds what has not been explored fully, and creates a fertile ground for further hypotheses that will lead to a more complete understanding of the apoptotic process.

The role of parasites and pathogens in the evolution of life history traits is of increasing interest to both ecologists and evolutionary biologists. Immunology, which was once studied almost exclusively by immunologists, has become an important area of proximate investigation to animal physiologists as a means for understanding changes in disease susceptibility and the neural and neuroendocrine mechanisms that mediate these changes. The coalescence of these different perspectives has given rise to the field of ecological immunology, an interdisciplinary research field that examines interactions among host physiology and disease ecology in a wide range of environmentally relevant contexts. The goal of ecological immunology is to understand immune function in the context of life-history traits across a wide range of organisms. Research within the field combines diverse approaches from a wide range of scientific disciplines including evolution, ecology, and life history theory to endocrinology, neuroscience, molecular biology, and behavior. This book critically reviews recent advances in the discipline of ecoimmunology. Chapters are written by experts in their respective fields and cover diverse topics including how environmental factors can affect host immune function, the complex dynamics among host immunity, pathogen prevalence and disease susceptibility, and the physiological mechanisms that lead to adaptive changes in immune responses. By integrating analyses of immune system function within animal biology, investigators will gain will gain a more comprehensive and satisfying understanding of organism-environment interactions at both ultimate and proximate levels of analysis.

This book was inspired by a gatheringofscientists in Los Angeles in 1994 under the auspices of the UCLA Clinical Nutrition Research Unit which is funded by the National Cancer Institute to promote new research into nutrition and cancer prevention. This unit supports research integrating basic and metabolic/clinical investigations which examine observations from epidemiologic studies and their application to the prevention ofcommon forms ofcancer through nutritional intervention. There is a great deal ofinformation from epidemiologic, experimental and metabolic studies implicating elements ofthe diet as important in the development and progression of common forms ofcancer including breast cancer, colon cancer, prostate cancer, and uterine cancer. When these forms ofcancerareexaminedcarefully, it isclearthat they share anumber ofcommon etiologic factors related to dietary fat, lipids, and hormones. A human cancer is usually discovered at a point where it has formed a detectable mass. For many forms of cancer, this may require 10 to 15 years from the time when the cancer is first initiated. Nutritional efforts at prevention may delay the progression ofcancer to a detectable mass resulting in reduced incidence and may retard the clinical progression and metastatic spread ofcancer after its primary treatment.

Neutrophils are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. However, during the beginning (acute) phase of inflammation, particularly as a result of bacterial infection and some cancers, neutrophils are one of first-responders of inflammatory cells to migrate toward the site of inflammation, firstly through the blood vessels, then through interstitial tissue, following chemical signals in a process called chemotaxis. This book presents topical data on neutrophils including neutrophils as biological age markers and predictors of longevity; the role of neutrophils in acute myocardial infarction, Behcet's Disease, bladder cancer, tuberculosis and others.

Autophagy is a fundamental biological process that enables cells to autodigest their own cytosol during starvation and other forms of stress. It has a growing spectrum of acknowledged roles in immunity, aging, development, neurodegeneration, and cancer biology. An immunological role of autophagy was first recognized with the discovery of autophagy's ability to sanitize the cellular interior by killing intracellular microbes. Since then, the repertoire of autophagy's roles in immunity has been vastly expanded to include a diverse but interconnected portfolio of regulatory and effector functions. Autophagy is an effector of Th1/Th2 polarization; it fuels MHC II presentation of cytosolic (self and microbial) antigens; it shapes central tolerance; it affects B and T cell homeostasis; it acts both as an effector and a regulator of Toll-like receptor and other innate immunity receptor signaling; and it may help ward off chronic inflammatory disease in humans. With such a multitude of innate and adaptive immunity functions, the study of autophagy in immunity is one of the most rapidly growing fields of contemporary immunological research. This book introduces the reader to the fundamentals of autophagy, guides a novice and the well-informed reader alike through different immunological aspects of autophagy as well as the countermeasures used by highly adapted pathogens to fight autophagy, and provides the expert with the latest, up-to-date information on the specifics of the leading edge of autophagy research in infection and immunity.

Phagocytosis has been at the forefront of cell biology for more than a century. Initially, phagocytosis, which comes from Greek words meaning “devouring cells,” was discovered in the late 19th century by Ilya Metchnikoff, who was awarded, together with Paul Ehrlich, the Nobel Prize in Physiology and Medicine in 1908 “in recognition of their work on immunity.” At that time Metchnikoff had already identified a function for phagocytes not only in host defense but also as scavengers of degenerating host cells during metamorphosis of tadpoles, thus providing one of the first descriptions of apoptotic cell clearance by macrophages (Kaufmann 2008). Since then, much has been learned about phagocytosis, and the previous several decades have witnessed outstanding progress in understanding the functions and the molecular mechanisms of phagocytosis. Two main types of targets are cleared by phagocytosis: microbial pathogens and dying cells. Rapid recognition and clearance of dying cells by phagocytes plays a pivotal role in development, maintenance of tissue homeostasis, control of immune responses, and resolution of inflammation. Clearance of dying cells can be divided into several stages, including sensing, r- ognition, binding and signaling, internalization, and immunological responses. In this book, our contributors address these different stages of dead cell cle- ance and examine how impaired clearance of dying cells may lead to human d- eases. We have attempted to provide sufficient cross-referencing and indexing to enable the reader to easily locate the ideas elaborated in the different chapters.

Tumor Necrosis Factor (TNF) is a member of a superfamily of proteins, each with 157 amino acids, which induce necrosis (death) of tumor cells and possess a wide range of proinflammatory actions. Tumor necrosis factor is a multifunctional cytokine with effects on lipid metabolism, coagulation, insulin resistance, and the function of endothelial cells lining blood vessels. Blocking the action of TNF has been shown to be beneficial in reducing the inflammation in inflammatory diseases such as Crohn's disease and rheumatoid arthritis. Inappropriate production of TNF or sustained activation of TNF signaling has been implicated in the pathogenesis of a wide spectrum of human diseases that include cancer, osteoporosis, sepsis, diabetes, and autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. Extensive research within the last two decades has shown that TNF can be a potential therapuetic agent in various diseases. This new important book gathers the latest research from around the globe in this field.

Programmed cell death (PCD) plays pivotal roles in tumor progression, cancer therapeutics and resistance of tumor cells to therapy. With the discovery of key mechanisms that are involved in mediating PCD and in promoting resistance to therapy, design of therapeutic approaches for promoting tumor-selective cell death has risen dramatically. With this book, we give a comprehensive overview of the mechanisms that are involved in mediating and regulating PCD in cancer. We also provide a detailed indication of the utility of PCD in cancer therapy. This book will be a valuable resource for researchers investigating the role of PCD in cancer and other diseases, researchers investigating the molecular mechanism of chemotherapeutic agents and drug-resistance in cancer and for physicians using chemotherapeutic agents. Additionally, this book will be a important educational source for PhD students specializing in cell biology, immunology and MD students interested in Oncology and Cancer Therapeutics.

In an effort to go beyond immune-based therapies, researchers are now considering the implications of apoptosis dysregulation during HIV-induced immunodeficiency. This work provides the first comprehensive compendium of the progress made in understanding the process of cell death related to HIV and the potential breakthroughs in treatment that offer much promise. Combining the work of more than two-dozen top researchers, this seminal volume provides clinicians and researchers with an excellent reference, while also serving as an incubator to stimulate future research. It explains the fundamental biology involved with apoptosis, explains its clinical impact in HIV, and examines the newest therapeutic approaches.

This book is an excellent, up-to-date reference on a relatively young area of research in which virology, cellular biology and molecular pathogenesis govern the principles of coinvestigation. Thus, the book will be of great interest to virologists, molecular immunologists and biologists, and biochemists but also to clinical pharmacologists in the long-term search for new antiviral agents. Ulrich Desselberger, Gif-sur-Yvette/Cambridge. Infection of a naïve (non-immune) host with a virus elicits an immediate response which results in a cascade of changes in the host, including an interferon response (innate immunity). The outcome of this interaction is influenced by the genes of the virus as well as the genes of the host. Interestingly, different viruses do it in different ways. Not only is there a plethora of mechanisms used by the invading organisms, but the host has also evolved a great variety of redundant and robust countermeasures. This interplay of host and virus represents one of the most significant frontiers in biology today. A clearer understanding of the mechanisms involved will arm us with better strategies to deal with viruses, including emerging pathogens and potential bioterrorism agents. This book is sure to benefit students, scientists, and physicians working in the areas of virology, immunology, microbiology, and infectious diseases. Pharmaceutical industry professionals will also find interest in this illuminating look into virus/host interactions.

Most of the diseases of modern mankind involve either acute or chronic inflammation. Measuring Immunity integrates the current information available on biomarkers and surrogate assays into a single handbook. It highlights the principles behind various applications, gives a brief summary on how they are conducted and provides detailed and critical analyses of murine models of immunity, clinical trials, and tests to predict utility and benefit. Measuring Immunity is indispensable for scientists and clinicians interested in the clinical applications of modern immunobiology.• Defines which assays of immune function are helpful in the assessment of clinical disorders involving inflammation and immunity• Assesses the dynamics of cellular and soluble factors in the peripheral blood using modern techniques • Includes basic science foundations as well as the approaches currently applied

Multiple Sclerosis (MS) is an enigmatic immune mediated disease of the central nervous system that affects about 350,000 individuals in the US, and many more around the world. The mechanism of this disease is largely unknown and there is no cure for it. However, there are several well-characterized experimental animal models that help us understand and speculate about potential mechanisms of pathology in this disease. Many of the experimental therapies designed for this disease rely on testing the drugs in animal models before using it in clinical trials. This book combines for the first time the different experimental models for MS (including immune-mediated and viral) under one roof, and highlights aspects that are different or shared among these experimental models. It's aim is to improve our understanding of this devastating disease and help us think about potential additional therapies for it.

As our understanding of apoptotic pathway expands, we are coming to realize the great potential of utilizing this pathway to treat diseases such as cancer. The book attempts to review, summarize, and speculate on the apoptotic pathways, how are they regulated and how targeted therapies are being used to treat a wide variety of diseases. Special emphasis is placed on cancer since new treatments either being developed or currently in the clinical setting are showing great promise to increase survival rates for cancer patients. Chapters will address the biology behind regulating the apoptotic pathways and what goes wrong in disease states whereas other chapters will concentrate on new therapies targeting apoptotic pathways. The reader by the end of the book should have greater insight into the understanding and utilization of apoptotic pathways to fight diseases such as cancer.

Immunohistochemistry is the use of specific antibodies to stain particular molecular species in situ. This technique has allowed the identification of many more cell types than could be visualized by classical histology, particularly in the immune system and among the scattered hormone-secreting cells of the endocrine system, and has the potential to improve diagnosis, prognosis and therapeutic options of cancer. This book discusses all aspects of immunohistochemistry and in situ hybridization technologies and the important role they play in reaching a cancer diagnosis. It provides step-by-step instructions on the methods of additional molecular technologies such as DNA microarrays, and microdissection, along with the benefits and limitations of each method. The topics of region-specific gene expression, its role in cancer development and the techniques that assist in the understanding of the molecular basis of disease are relevant and necessary in science today.• The only book available that translates molecular genetics into cancer diagnosis • The results of each Immunohistochemical and in situ hybridization method are presented in the form of color illustrations • Methods discussed were either developed or refined by expert contributors in their own laboratories

Advances in Immunology presents current developments as well as comprehensive reviews in immunology. Articles address the wide range of topics that comprise immunology, including molecular and cellular activation mechanisms, phylogeny and molecular evolution, and clinical modalities. Edited and authored by the foremost scientists in the field, each volume provides up-to-date information and directions for future research. - Interactions between NK Cells and B Lymphocytes - Multitasking of helix-loop-helix proteins in lymphopoiesis - The pathogenesis of Diabetes in the NOD Mouse

The fourth edition of The Cytokine Handbook provides an encyclopedic coverage of the molecules that induce and regulate immune responses. Now expanded to two volumes, co-edited by Michael T Lotze, and written by over 120 international experts, the scope of the book has been broadened to include a major emphasis on the clinical applications of cytokines. The early chapters discuss individual cytokines, chemokines and receptors. Additional chapters discuss the clinical implications and applications of cytokines, including cytokine gene transfer, antisense therapy and assay systems. This book is essential for researchers and clinicians interested in cytokines, including anyone working in cancer biology, transplantation, infectious diseases, autoimmunity or bioinformatics.Key Features• Covers all main cytokines and chemokines • Written by experts• Up-to-date- includes detailed referencing accessing current, modern literature and reflects the newest findings from the human genome • The new edition has been thoroughly revised and extended (now 2 volumes) as compared to the last edition, including new co-editor (MTL), new authors, new hot topics and new chapters• Includes major emphasis on clinical applications• Extensively illustrated with tables and figures

Advances in Cancer Research

Advances in Virus Research

The present volume is the first in the advances in oncobiology series. It is meant to be useful not only to clinical and non-clinical oncologists but also to graduate students and medical students. The individual chapters are presented as self-contained summaries of current knowledge rather than as reviews. The last chapter deals with the subject of chemotherapy.

In any movement of their life, immune cells, especially T and B lymphocytes, are confronted with an essential choice: to continue their existence or to commit a sort of metabolic suicide that is referred to as apoptosis or programmed cell death. In contrast to most philosophers, lymphocytes and their precursors are constantly susceptible to suicide, and it even appears that the usual cause of T or B cell elimination is suicide rather than death from natural causes, accidents or murder. This book provides a vast overview of lymphocytes suicide: external triggers and internal motives leading to suicidal impulses, accomplices in self-destruction, weapons implicated in self-execution, removal of dead bodies and pharmacological prevention of suicide. Most of the chapters in this book are devoted to the physiology of apoptosis. The goal is to unmask the external triggers of apoptosis, unravel the signal transduction pro­ cesses involved therein and describe the role of oncogenes,'death genes'and effector molecules in the apoptotic cas­ cade. The remaining chapters deal with the pathophysiologi­ cal aspects of lymphocyte apoptosis, namely, as a host contribution to HIV-induced lymphopenia, and therapeutic strategies for the avoidance of lymphocyte death. We are confident that this compendium will contribute to the exploration of cellular suicide, not only from a basic scientist's viewpoint but also with regard to the possible clinical implications of apoptosis (dys)regulation. Far from having a depressing effect on the reader, cellular suicide may thus provide a source of both intellectual excitement and therapeutic inspiration.

At first glance the destruction of a target cell by a killer cell seems to be a simple endeavor. A closer look, however, reveals the complex mechanisms underlying this task. Killer cells are able to specifically recognize altered or infected cells. A transient contract with target cells has to be established to allow the delivery of lethal molecules or signals. The killer cell then disengages from the damaged cell and moves away to kill other target cells. After the eradication of the target cells, the number or activity of activated killer cells has to be reduced to avoid nonspecific killing of innocent cells. In 1992, Herman Eisen concluded, in his introductory remarks in the most recent volume on lymphocyte cytotoxicity (EISEN 1993):'Given the immense amount of effort made in the past decade to understand these (lytic) mechanisms, it seems surprising that a consensus about the principal mechanisms has not been reached.'Since that time, advances made in the field of cell-mediated cytolysis are so significant that our knowledge regarding the lytic mechanisms has been considerably augmented. Much of this is due to studies with transfectants and mutants-either naturally occurring or generated by gene targeting. It is now clear that there are two predominant pathways which act hand in hand and lead to efficienttarget cell destruction.

There has been a dramatic increase in the perception of the value of animal cell biotechnology to the research and manufacturing communities in recent years. This volume seeks to keep the reader up-to-date with this progress. This sixth and final volume in the series concentrates on the biology of animal cells in culture, giving special attention to the relationship between biology and the ability to use such cells productively. As the search continues for greater productivity, there is a need to understand the switches within cells that control expression. Additional abilities to manipulate those switches in a controllable manner are also required. In the last five years, considerable progress has been made in the elucidation of the mechanisms for cell signaling and control of gene expression. The 13 chapters of this volume are devoted to these subjects and to techniques in areas of particular concern in manufacturing circles. The achievements in the field to date are described in this book, which, together with its five companion volumes in the series, will provide a building block for the future development of animal cell biotechnology.

Volume 71 of Advances in Cancer Research begins with Morgan and Kastan presenting data on the roles of p53 and ATM in cell cycle progression and cell death in response to DNA damage and how this information may lead to targets for improved cancer therapies. Kok et all. Review the methodological advantages and limitations to localizing tumor suppressor genes, especially those on the short arm of chromosome 3. Peltomaki and de la Chapelle describe research on mismatch repair genes and their effects on colorectal cancer. McKenna and Cotter present findings on the functions and failures of apoptosis in the hematopoietic system. Ravitz and Wenner review TGF-B and how it controls and affects cell cycle progression in a variety of cell types. Andrew Simpson presents data on the mutation frequencies of microsatellites in human carcinogenesis. Naor and colleagues present research on a multitude of tumors expressing levels of CD44 and discuss how CD44 may be used as a target for cancer therapy. Luisa Villa discusses various aspects of HPV and the potential clinical use of HPV testing in cervical cancer prevention programs. Last, Disis and Cheever review the studies that define HER-2/neu specific immunity in patients with cancer and the current vaccine strategies for generating specific immunity.

Experimental and Comparative Toxicology, Volume 31 aims to explore some of the potentially important and crucial areas in experimental toxicology. The book discusses tumor promoters and genotoxic chemicals in short-term testing for carcinogenicity, as well as the significance of preneoplastic liver lesions in experimental animals. The text also describes the factors known to be associated with increased risk of liver neoplasia as a human disease, and the extent to which it is known that the same factors have a similar effect in laboratory animals. Neurobehavioral toxicology; immunotoxicology; and the endocrine system as the target in experimental toxicology are also considered. The book further tackles the uses of gamma-glutamyltransferase in experimental toxicology, as well as the predictive value of ocular irritation tests. Toxicologists, biochemists, pathologists, and those involved in preventive medicine and community health will find the text invaluable.