Given the latest advances in cancer research, which includes basic research and its derived diagnostic, clinical, and therapeutic applications, the book New Trends in Cancer for the 21st Century is written by individuals such as molecular biologists, whose tasks are to decipher, after sequencing the human genome, those new genes and pathways involved in the carcinogenesis process; clinical and molecular pathologists, who apply these discoveries for the molecular diagnosis and characterization of the tumor; and clinical oncologists, who treat patients. Pharmacogenetics introduces new perspectives in the translational fields with the design of drugs against specific targets, which at this moment are in clinical trials phases. This book achieves a state of the art in every field of cancer research and discusses the new perspectives that will open the future for cancer treatment (basic research, new technologies, new drugs, therapies...). For this reason, the book is intended for pathologists, clinicians, and biologists, as well as fellows and students of physiology and medicine.

Glycotechnology brings together in one place important contributions and up-to-date research results in this fast moving area. Glycotechnology serves as an excellent reference, providing insight into some of the most challenging research issues in the field.

First published in 1992, this volume provides a systematic survey of the dibenzanthracenes and of their chemical, physiochemical and biological properties. The carcinogenic potential of the dibenzanthracenes - an important subclass of polycyclic aromatic hydrocarbons - has been extensively studied and documented since their identification as animal skin carcinogens was first demonstrated in the 1930s. the volume treats the nomenclature, the chemical and physical properties and the synthesis and preparation of the five principal isomers of the dibenzanthracenes series: dibenz (a, h), - dibenz (a, c), -dibenz (aj) anthracene, benzo(a)naphthacene and pentacene. Other chapters are devoted to their occurrence and analysis in the environment, in industrial processes and effluents, and in foodstuffs. The second part addresses their biological activity and reviews the metabolism, cellular interactions, toxicology mutagenicity and carcinogenicity of the dibenzanthracenes. The final chapter is devoted to structure-activity relationships in this class of aromatic compounds. This is the first comprehensive account of this important group of environmental pollutants and carcinogens. It will be of interest to all scientists studying carcinogenesis, and the mutagenicity and toxicology of environmental pollutants.

First published in 1988, this volume surveys the chemical synthesis and biological activity of the benz a]anthracenes. These compounds occur in smoke and mineral oils and a few have been shown to be potent carcinogens. This volume was the first to review, systematically and in depth, the organic synthesis of these compounds as well as their metablolism, interactions with nucleic acids and protein, mutagenicity and carcinogenicity. Such studies have important implications in determining mechanism and specificity of chemically induced carcinogenesis.

Twenty years ago when Children's Cancer Association of Japan was born, the diagnosis of childhood leukemia amounted to a death sentence. Only 20% or so of children with leukemia survived more than 5 years. Since then, enormous improvements have been achieved regarding our understanding on the etiology, diagnosis, and the treatment of childhood leukemia. Now, 70% of children with leukemia survive and enter adult life. Even though the improved survival rate of children with leukemia represents a medical success story, we now face new problems. The first problem is the fact that we still lose 20-30% of patients with childhood leukemia. To address this problem, we need to understand the etiology, epidemiology, and biology of leukemia; to identify the patients at greater risk; and to develop adequate treatments. The second problem is the treatment itself. Even though efficacious, the modem treatment for leukemia is a grueling experience for children and their families. We should develop a total care system for families and children based on a deep understanding of their needs. The third problem is the aftereffects of the treatment and of cured leukemia. Extensive radiation and chemotherapy have an entirely different spectrum of long-term effects on children than on adults. These treatments in the early stage of life, when the mind and body are developing, create many physical and psychological problems. These are the present problems of childhood leukemia.

The purpose of this book-the fourth volume of a series on Can cer Markers-is intended to provide an updated "status report" on today's use of cancer markers in the diagnosis and monitoring of can cer, with an emphasis on cancer markers detected in the serum. It has been 7 years since the publication of the last volume in this series. The 1980, 1982, and 1985 volumes covered the development of cancer markers, not only in their roles of unraveling the basic biology of can cer, but also as increasingly important players in the management of patients with cancer. During the last 7 years we have seen the applica tion of a number of markers identified by monoclonal antibodies, as well as the beginnings of the use of genetic markers defined by mo lecular probes. Measurements of oncogenes in tissues or cells prom ise many applications for the future, but as yet, these genes have not shown to be useful as serum markers of cancer. The commercial interest in serum markers for cancer, particu larly for the diagnosis and monitoring of tumor patients, is indicated in Chapter 24 by Owen, where the total worldwide market for cancer markers is projected to increase from $148 million in 1988 to $232 million in 1993. The degree of research interest in cancer markers is reflected in the fact that in 1988 a separate category for tumor mark ers was added to Index Medicus.

Neurosurgery o/the Future: Computers and Robots in Clinical Neurosurgical Practice and in Training - a Philosophical Journey into the Future Many present day neurosurgeons believe that they already obtain good results in operative surgery with the benefit of the operating microscope and other aids which have become available in the last three decades and that the introduction of computers and robots to the operating theatre is superfluous. However, it is clear from analogy with the function of the airline pilot, another profession where there are great demands on manual skill and on spatial awareness, that these devices do have much to offer neurosurgery. Classical neurosurgery, in the time of Cushing, Dandy and Scarff, was based on a three dimensional picture of the patient's brain formed in the surgeon's mind and often illustrated in elegant drawings. Such pictures were based on neuroradiological studies by pneumoencephalography, ventriculography or by angiography. Generally these stud ies showed the presence and position of a lesion by displacement of normal brain structures and the picture was built up by interference. This was then converted by the experienced neurosurgeon into a plan for the craniotomy site and the trajectory of the surgical approach. Once the brain was exposed further pre-operative information was obtained by visual inspection and by palpation with the brain needle. These classical forms ofneuroradiology have largely been superseded by computerised tomography and by magnetic resonance imaging."

Rubin and Damjanov's latest volume of Pathology Reviews highlights the latest progress in the interface of biology and disease. Forefront techniques and experimental models that were once considered exotic or esoteric, are explored here in the context of understanding more fully the processes involved in human disease. Topics include: regulation of liver growth * contractile cells in lungs * mineral formation in bone * folate metabolism * the "riddle of the mast cell" * HLA antigens * interleukin 6 * IgA nephropathy * Goodpasture syndrome * anti-basement membrane glomerulonephropathy * molecular mechanisms of oncogenesis * molecular diagnosis of cancer * inhibition of intercellular communication in carcinogenesis * DNA repair and its pathogenetic implications * human and rat mammary tumorigenesis. Pathology Reviews * 1990 is essential reading for everyone concerned with the mechanisms of disease.

Alcohol and other drugs of abuse are major contributing factors to liver disease and its pathology. Alcoholic cirrhosis causes thousands of deaths each year in the United States, and encourages liver replacement. A better understanding of the mechanisms of liver pathology will significantly aid basic researchers and physicians in treating and preventing liver damage. This book is designed especially for those researchers wishing to understand alcoholic liver disease. Therefore the role of alcohol in changing nutrition and its nutritional effects on liver disease are reviewed. The generation of free radicals during alcohol use has been found to be an important cause of membrane changes, of cancer development, and of lipid alterations-and thus of liver pathology. In addition to alcohol, other drugs of abuse, including morphine, cocaine, marijuana, and caffeine have also been shown to be significant contributors to liver pathology. The prevalence of drug and alcohol use and abuse today means that liver disease will continue as a major social and medical problem. The explanation of its biological origins cannot fail to help us better understand and treat the disease in the years to come.

Specialists from diverse disciplines discuss the important topics of Tissue Repair and Fibrosis. The Role of Myofibroblast. The Myofibroblast is implicated in many processes, such as tissue repair, fibrosis, and stromal reaction to tumors. This book seeks to provide an overview of the knowledge accumulated since this cell was first describes 25 years ago. Discussions focusses on three main topics: - Cellular and molecular biology of fibroblast and myofibroblasts - Wound healing: experimental models, and - Human fibrocontracted diseases

Needle biopsy of the liver is now an accepted procedure in most large hospitals, and surgeons and laparoscopists are more likely to biopsy the liver under direct vision than in the past. Consequently, increasing demands are being made on pathologists for rapid diagnosis. This full colour atlas provides a practical guide to the histopathological diagnosis of liver disorders, with particular emphasis on clinicopathological correlation and the need for the pathologist to be in full possession of all the available clinical information. Although containing over 350 colour illustrations, the book is more than just an atlas and each section includes a brief description of the main clinical and pathological features of the subject under discussion. For this second edition, many chapters have been rewritten - e.g. on viral hepatitis - and many new illustrations added. The book is intended for the practising and trainee pathologist and the clinician who performs liver biopsies, but will also be of value to postgraduates, residents and students in other branches of medicine.

This comprehensive book, lavishly illustrated with over 700 colour pictures, addresses the subject of bone in internal medicine. It is based on biopsies of bone and first describes the normal range of physiological findings in iliac crest biopsies in young, middle-aged and elderly individuals. The book then deals systematically with the osseous disorders most frequently encountered in internal medicine, and some that would be considered in the differential diagnosis. Numerous up-to-date references are included. The clinical applications of biopsies of bone are emphasized as well as their clinical interpretation; sections on histomorphometry and functional aspects of bone cells are also included. The book will be of particular interest to specialists in internal medicine, endocrinology, nephrology, haematology and oncology, as well as being a bench manual for the practising pathologist.

The localized attachment of circulating leukocytes to endothelium has been recognized as the cellular hallmark of the inflammatory response. This adhesive interaction, a necessary antecedent to the emigration of leukocytes from the blood into the tissues, is mediated by vascular adhesion molecules. Leukocyte Recruitment, Endothelial Cell Adhesion Molecules and Transcriptional Control: Insights for Drug Discovery outlines some of the cellular and molecular mechanisms of inflammation with contributions from top researchers. This volume provides an overview of three of these endothelial adhesion molecules, as examples of key mediators of leukocyte recruitment. It reviews the structure and regulation of these cell surface proteins and focus on the rapidly expanding field of transcriptional regulation of these inducible proteins, and closes with a discussion of drug discovery possibilities that target the regulation of leukocyte recruitment. This book will be of interest for any researchers, in academia or industry, looking for an overview of leukocyte recruitment or novel approaches to drug discovery.

As an industry, biotechnology may be likened to the Hymn Book, being both ancient and modern. Whereas activities such as baking, brewing, the fermenting of foods date from our earliest attempts to control and utilise the environment, the application of recombinant DNA technology is recognised as being at the forefront of novel industrial development. Perhaps because of its association with processing foodstuffs together with the benefits derived from applications in the early organic chemistry and pharmaceutical industries, biotechnology has been regarded as being inherently safe. Yet unlike other modern industries, such as chemical and nuclear, where regulation has followed from incidents or accidents, modern biotechnology has been subject to close scrutiny and regulation almost from its inception. The process of regulation itself is somewhat unusual in that it was initially self-imposed by the very scientists who developed the fundamental techniques of recombinant DNA technology. They recognised the signific ance of their development but were concerned of the effects on humans and the environment of uncontrolled application of the new, powerful technology. Concern about the possible consequences of genetic manipula tion has undoubtedly been the driving force behind the regulations that are now in place in many parts of the world and which are the subject of this book. Safety issues in the biotechnology industry can be categorised under three headings: worker, environmental and consumer (product) safety."

In the last decade tremendous progress has been made in the diagnosis and treatment of tumours of the mediastinum. The use of immunohistochemistry, molecular biology, electron microscopy, CT and MRI, and a better knowledge of tumour markers, has made for better diagnosis, often without the need for biopsy, in many cases. This in turn has clarified the classification and thus the epidemiology of tumours of the mediastinum, and modern radiotherapy, chemotherapy and surgery has led to improved survival of patients at risk. With over 300 illustrations, mostly in full colour, and a well-referenced text, this atlas is an invaluable bench reference for the practising diagnostic pathologist and a study aid for the trainee, as well as a comprehensive source of reference for oncologists and surgeons.

The 1997 European Conference on Spectroscopy of Biological Molecules (ECSBM) is the seventh in a biennial series of conferences devoted to the applications of molecular spectroscopy to biological molecules and related systems. The interest of these conferences rests mainly on the relationship between the structure and physiological activity of biological molecules and related systems of which these molecular species form part. This volume ofECSBM contains articles prepared by the invited lecturers and those making poster presentations at the seventh ECSBM. The reader will find mainly applications of vibrational spectroscopy to protein structure and dynamics, biomembranes, molecular recognition, nucleic acids and other biomolecules and biological systems containing specific chromophors. Biomedical applications of vibrational spectroscopy are expanding rapidly. On the other hand, a significant number of the papers describe applications of other methods, such as NMR, circular dichroism, optical absorption and fluorescence, X-ray absorption and diffraction and other theoretical methods. One aim has been to achieve a well balanced, critically comparative review of recent progress in the field of biomolecular structure, bonding and dynamics based on applications of the above spectroscopic methods. A great part of the contributions included in this volume are devoted to biomedical and biotechnological applications and provide a broadly based account of recent applicationS in this field. The content of this book has been organized in sections corresponding mainly to the different types of biological molecules investigated. This book includes also another section related to theoretical methods where MO calculations of vibrational frequencies dominate clearly the topic.

Advances in biochemistry, cell biology, genome-wide mutagenesis - coupled with molecular technology, including gene microarray and transgenic and knock-out animals - have been instrumental in understanding the cellular processes and molecular pathways of self-tolerance and autoimmune diseases. The molecular definition of these pathways and processes has led to novel treatments for certain auto-immune diseases that are based on the pathogenesis of diseases rather than on broad-spectrum immunosuppression. This book reviews many of these current developments and proposes future novel approaches for understanding the pathogenesis of auto-immune diseases and designing novel therapy. This book covers three major areas of auto-immunity: the basic mechanisms of immunological tolerance, pathogenesis of auto-immune diseases, and some novel therapies. This book should be useful for immunologists, molecular biologists, rheumatologists, and clinical scientists.

Principles of Insect Pathology, a text written from a pathological viewpoint, is intended for graduate-level students and researchers with a limited background in microbiology and in insect diseases. The book explains the importance of insect diseases and illuminates the complexity and diversity of insect-microbe relationships. Separate sections are devoted to * the major insect pathogens, their characteristics, and their life cycles * the homology that exists among invertebrate, vertebrate, and plant pathogens * the humoral and cellular defense systems of the host insect as well as the evasive and suppressive activities of insect disease agents * the structure and function of passive barriers * the heterogeneity in host susceptibility to insect diseases and associated toxins * the mechanisms regulating the spread and persistence of diseases in insects. Principles of Insect Pathology combines the disciplines of microbiology (virology, bacteriology, mycology, protozoology), pathology, and immunology within the context of the insect host, providing a format which is understandable to entomologists, microbiologists, and comparative pathologists.

Endoscopic neurosurgical interventions gain in importance. This book gives adetailed description of the recent indi- cations of endoscopic procedures inmodern neurosurgery. They include endoscopic stereotaxy, endoscopic evacuations of intracerebral hematomas, cysts and abscesses as well as endoscopic interventions on brain tumors. An extended over- view about the usable endoscopes and the operative equipment is pointed out

VEGF and Cancer is a comprehensive and up to date review of current knowledge on the role of vascular endothelial growth factor (VEGF) in cancer. Key Features: -Discussion of VEGF as potent angiogenic factor and its role in tumor angiogenesis, -Review of the biology, molecular properties and regulation of VEGF, -Discussion of the role of VEGF in a range of different tumor types, both solid tumors and haematological cancers, -Review of the therapeutic potential of different approaches to block VEGF, -Review of recent evidence that in addition to its role as an endothelial cell mitogen, VEGF may also be an autocrine growth factor for tumor cells, regulating survival and invasion. This book is aimed at scientists new to angiogenesis and VEGF biology and provides new information for established researchers and scientists. It will also be a useful text for clinicians interested in anti-angiogenic therapy for treatment of human cancers.

Historically we have separated the disciplines of Chemistry and Biochemistry by recognizing that the distinguishing characteristic of Biochemistry is the catalysis of reactions by enzymes. Enzymes permit metabolic reactions which would otherwise require extremes of temperature, pressure or pH, often associated with Chemistry, to proceed under ambient conditions of the body. Under some conditions chemical reactions occur in vivo in which products of enzymatic reactions proceed to undergo further reactions non- enzymatically with cellular macromolecules. The results can often be seen as toxic or carcinogenic responses. The chemicals that initiate these reactions are termed "biological reactive intermediates. " The International Symposia on Biological Reactive Intermediates (BRI) began in 1975 at the University of Turku, Finland and have since convened at the University of Surrey, Guildford, The United Kingdom (1980), the University of Maryland, College Park, Maryland (1985), the University of Arizona, Tucson, Arizona (1990), the GSF Forschungszentrum and Technical University of Munich (1995) and, most recently, at the Universite Rene Descartes, Paris, France (2000). The Symposium was organized by an International Planning Committee co-chaired by P. Dansette (Paris, France) and TJ. Monks (Austin, Texas). The committee included: P. H. Beaune (Paris, France), M. De\aforge (Saclay, France), G. P. Gervasi (Pisa, Italy), G. G. Gibson (Guildford, UK), H. Greim (Munich, Germany), DJ. Jollow (Charleston, South Carolina), P. Moldeus (Sodertalje, Sweden), I. G. Sipes (Tucson, Arizona), R. Snyder PJ. van Bladderen (Zeist, The Netherlands). They were (Piscataway, New Jersey), and assisted by an International Scientific Program Advisory Committee which included: TJ.

INHALT: The Concept of the BBB: an Historical Perspective Anatomy of the BBB Pathophysiology of BBB * Brain oedema Breakdown of the BBB BBB Dysfunction after SAH * Clinical Monitoring Neuroradiological Evaluations of BBB Dysfunction after SAH * Computerised Tomography and Magnetic Resonance * SPECT and PET Experimental Data * Literature Review of BBB Dysfunction after Experimental SAH * Qualitative Assessments * Quantitative Assessments * Time Course of BBB Dysfunction after SAH * Additional Pathophysiological Changes after SAH - Cerebral Vasospasm - CSF Eicosanoids - Cerebral Metabolism - Behavioural and Neurological Deficits - Intracranial Pressure - Blood Pressure, Blood Gases, Plasma pH, Plasma Glucose, Body Temperature Strategies for Pharmacological Interventions * Hydroxyl Radical Scavenger AVS * Glutamate Antagonist Felbamate * Calpain Inhibitor II Challenges and Future Directions * Advances in Cerebrovascular Pathophysiology Elucidation * Gene Therapy

The first Symposium on ~iammary Pathology organized by the International Society against Breast Cancer was held in Paris on December 3-7, 1979. The programme was divided into sections with morning lectures on current topics in mammary pathology given by invited speakers, followed by discussions, and, in the afternoon, emphasis on practical work, such as slide seminars, technical explanations of tissue and cell preparations for histology, cytology, electron microscopy and tissue culture work. The morning sessions were held at the Racing Club of France, 5 rue Eble, 75007 Paris and the organizers of the meeting wish to thank the RCF andits President, Mr. R. Menard for their kindness and generous help in the arrangement of the symposium. The afternoon workshops too~ place at the Institut de Pathologie et de Cytologie Appliquee {Director Professor J. de Brux) , rue des BeIles Feuilles, Paris XVI, with the help of staff members from this Institute. The editors of the Proceedings of the Symposium wish to thank the contributors for their help in providing manuscripts for publication and for complying with the instructions given by the editors and the Plenum p;ubli- shing Company. Financial supports providea by the Ligue Nationale Fran9aise contre le Cancer and the FEGEFLUC are gratefully acknowledged. It is hoped that the present volume will provide stimuli for future work on clinical and basic research in mammary pathology.

It is well known that estrogen is "somehow a protective hormone for various age-related disorders. This book provides a solid knowledge of estrogen s neuroprotective activities in the brain with a special emphasis on neurodegenerative disorders such as Alzheimer s Disease. The focus is (1) to describe the biochemical, molecular, and cellular basis of the protective activity of estrogen and (2) to transfer this knowledge into the hospitals by discussing preventive and therapeutic approaches such as estrogen replacement therapy for post-menopausal women. Besides up-to-date information on estrogen and the brain, this book explains in a highly understandable manner molecular and cellular techniques by which basic data have been collected. The reader, which may include the professional specialist as well as the interested non-specialist, will also gain insight into the scientific transfer process of knowledge from basic science to the clinical situation and therefore "from bench to bed ."

This book is based upon a series of papers originally presented at a NATO Advanced Studies Workshop of the same title held at the study Center HI Cappuccini," a converted monastery in San Miniato, a small village located between Pisa and Florence, Italy, in October 1991. Authors were asked to submit their completed chapters by the following February; these were then scanned onto computer disks, edited and returned to the authors for final revision, and updating, with a final deadline of February 1993. The authors were encouraged to make whatever modifications they wanted, especially regarding updating their chapters, with an eye to making the final product both comprehensive and current. In this we succeeded beyond our expectations, with most chapters extensively altered and many completely re-written and significantly expanded. Thus, although the original meeting was held in 1991, the chapters in this volume may be regarded as current from at least February, 1993, with some of the final updated revisions received as late as July, 1993. This book, as agreed in our original contract, has been delivered to the publisher "camera-ready. " This means that all of the scanning, editing, proofing and typesetting were done here, by the office of the Department of Dermatology at the New Jersey Medical School. We essentially produced the book, which the publisher, for the most part, then photocopied. This has been an enormous burden, borne mainly by my colleague in this division, Robert A.