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The book offers a comprehensive overview of all parathyroid gland disorders both, benign and malignant. It emphases established concepts, presents the ongoing controversies, challenges and debates on diagnosis and treatment of different parathyroid gland disorders, with a view of clarifying some uncertainties, making suggestions to resolve others, and establishing strategies to reach therapeutic success.In addition to general information on parathyroid gland embryology, surgical anatomy, histology and physiology, the chapters explore hyperparathyroidism, osteitis fibrosa cystica, hypoparathyroidism, hungry bone syndrome, the importance of calcium in the human body and differential diagnosis of hypercalcemia. The last chapters investigate post-thyroidectomy hypocalcemia, thyroid cancer, recent intra-operative localizing tools, and illustrate new techniques of parathyroidectomy, as well as parathyroid transplantation. The book will be an invaluable and indispensable source of knowledge and reference for all specialists and trainees entrusted with the care of patients suffering from parathyroid disease.

The book provides a comprehensive overview of classic and modern approaches of centrosome research, including new aspects of centrosome functions focusing on primary cilia and their implications in numerous diseases. In addition, several chapters raise awareness of centrosomes in areas that have not yet fully considered the centrosome as an organelle that impacts other organelle functions directly or indirectly. It further relates centrosome functions to other research areas such as aging and stem cell research. Since its discovery almost 150 years ago the centrosome is increasingly being recognized as a most impactful organelle for its role, not only as primary microtubule organizing center (MTOC) but also as a major communication center for signal transduction pathways and as a center for proteolytic activities. Its significance for cell cycle regulation has been well studied and we now also know that centrosome dysfunctions are implicated in numerous diseases and disorders including cancer, cystic diseases of the kidney, liver fibrosis, cardiac defects, obesity and several other diseases and disorders. This new volume reviews the latest advances in the field and provides valuable background information that is readily understandable for the newcomer and the experienced centrosome researcher alike. Due to the interdisciplinary of the subject, it is a valuable resource for researchers and clinicians working in biomedical research, cell biology, cancer biology, reproduction and developmental biology, neuroscience and stem cell research.

Bone Cancer, Second Edition comprehensively investigates key discoveries in the field of bone biology over the last five years that have led to the development of entirely new areas for investigation, such as therapies which combine surgery and biological approaches. The Second Edition expands on the original overview of bone cancer development (physiology and pathophysiology), with key chapters from the first edition, and offers numerous new chapters describing the new concepts of bone cancer biology and therapy, for both primary bone tumors as well as bone metastases. Each chapter has been written by internationally recognized specialists on the bone cancer microenvironment, bone metastases, osteoclast biology in bone cancer, proteomics, bone niche, circulating tumor cells, and clinical trials. Given the global prevalence of breast and prostate cancers, knowledge of bone biology has become essential for everyone within the medical and cancer research communities. Bone Cancer continues to offer the only translational reference to cover all aspects of primary bone cancer and bone metastases – from bench to bedside: development (cellular and molecular mechanisms), genomic and proteomic analyses, clinical analyses (histopathology, imaging, pain monitoring), as well as new therapeutic approaches and clinical trials for primary bone tumors and bone metastases. - Presents a comprehensive, translational source for all aspects of primary bone cancer and bone metastases in one reference work - Provides a common language for cancer researchers, bone biologists, oncologists, and radiologists to discuss bone tumors and how bone cancer metastases affects each major organ system - Offers insights to research clinicians (oncologists and radiologists) into understanding the molecular basis of bone cancer, leading to more well-informed diagnoses and treatment of tumors and metastases - Offers insights to bone biologists into how clinical observations and practices can feed back into the research cycle and, therefore, can contribute to the development of more targeted genomic and proteomic assays

Cilia are tiny microtubule-based organelles projecting from the plasma membrane of practically all cells in the body. In the past 10 years a flurry of research has indicated a crucial role of this long-neglected organelle in the development and function of the central nervous system. A common theme of these studies is the critical dependency of signal transduction of the Sonic hedgehog, and more recently, Wnt signaling pathways upon cilia to regulate fate decisions and morphogenesis. Both primary and motile cilia also play crucial roles in the function of the nervous system, including the primary processing of sensory information, the control of body mass, and higher functions such as behavior and cognition, serving as'antennae'for neurons to sense and process their environment. In this book we describe the structure and function of cilia and the various tissues throughout the brain and spinal cord that are dependent upon cilia for their proper development and function.

Primary liver cancer is a rather unusual malignancy in that the incidence varies tremendously from one geographical area to another. While relatively uncom­ mon in Western countries, it is the most prevalent malignant neoplasm in Southeast Asia, South Africa, and many other regions; in all, the countries in which primary liver cancer is very prevalent account for more than two-thirds of the world's population. In China alone, approximately 100 000 people die every year from primary liver cancer, mostly hepatocellular carcinoma. The incidence is rising in some countries, especially Japan, where it has doubled among males in the past 15 years or so, a staggering and puzzling trend. Since the demonstration of an etiological relationship between hepatitis B virus infection and hepatocellular carcinoma, intensive research has been con­ ducted in an effort to elucidate the role of the virus in hepatocarcinogenesis. Though much progress has been made, a full understanding of the molecular events leading to malignant transformation of the hepatocyte will probably require many more years of rigorous investigation. Chemical carcinogens and several industrial pollutants may also be involved in the etiopathogenesis of neoplastic liver disease.

It is now widely accepted that cells have the ability to initiate a program of gene-directed death, a process called'apoptosis'which may also be used as an innovative strategy for therapeutic intervention in cancer therapy. Experts in this area report on the regulation and control of apoptosis in hormone dependent (neoplastic) tissue and the possibility to exploit active cell death for therapeutic application.

This volume provides a comprehensive, highly readable overview of the topics discussed at the First International Symposium on'Vitamin D Analogs in Cancer Prevention and Therapy'held in Homburg/Saar, Germany in May 2002. Leading researchers discuss our present knowledge of the vitamin D system in cancer. Topics range from the newest findings in molecular biology, epidemiology, synthesis and metabolism of vitamin D to new concepts for the use of vitamin D analogs in cancer prophylaxis and treatment. The book provides essential up-to-date information for every researcher or clinician interested in the biology of vitamin D or cancer.

The book will discuss the molecular mechanisms of cancer diseases, stem cell proliferation and transformation into cancer cells beyond the physiological processes that occur in normal stem cell biology. Some of the key oncogenic events in cancer and their signaling pathways that regulate cell division cycle progression will be described considering prospects for using such knowledge in advanced cancer therapy. Each chapter shall provide an invaluable resource for information on the most current advances in the field, with discussion of controversial issues and areas of emerging importance

While serendipity and random screening continue to fulfil a significant role in the search for new drugs, current remarkable advances in molecular biology and genetics are dictating to a profound extent the approaches employed in their development. Increasing attention is being devoted to investigations of the mechanisms of action of existing drugs, and the sources of undesired side effects, at the molecular level. The information so derived is now extensively applied, with the aid of broad inter­ disciplinary approaches, both theoretical and experimental, to improvements in existing drugs, and the rational design of new ones. The foregoing comprised the subject matter of the 3rd Inter­ national Symposium on'Molecular Aspects of Chemotherapy', under the auspices of the International Society of Chemotherapy, and organized by the Committee on Drug Research, Polish Academy of Sciences, and the Department of Biotechnology and Biochemistry, Technical University of Gdansk. This volume includes the texts of the review lectures presented by invited participants on up-to-date achievements, and future perspectives, in molecular mechanisms of inhibition of cellular functions and metabolism, with emphasis on the design and mechanisms of action of chemotherapeutic agents for treatment of bacterial, neoplastic, viral and parasitic diseases. From the Contents, it will be seen that the range of disciplines represented was a broad one, including theoretical and experimental chemists, physicists, molecular biologists, biochemists, enzymologists, virologists, tumour biologists. Plenary sessions were supple­ mented by several poster sessions.

During the last years much attention has been given to the investigation of the roles of specific growth modulators acting on liver cell populations. HGF functions as a pleotropic factor in the liver as well as in other extrahepatic tissues. The hepatic stem cell compartment is thought to play a major role in liver tissue restoration. Mechanisms of cell growth and cell death of the liver are described in detail, with particular emphasis on apoptosis. The functions of HBV-pX protein and the roles of hepatitis B virus gene expression relation to hepatocellular carcinoma are discussed. Techniques for obtaining human and nonhuman hepatocytes and other liver cell types and for efficient transfer and expression of genes in hepatocytes and liver-derived cell lines are presented.

A wide variety of hormones, neurotransmitters and growth factors exert their cellular effects by reacting first with membrane receptors resulting in an increase of intracellular calcium and the cellular response. The calcium signal in the cell is mediated by the high-affinity calcium binding proteins (characterized by the EF-hand structural element), and by the calcium and phospholipid dependent proteins. Many of these have been discovered most recently. Their purification, distribution, protein and gene structures as well as their physiological roles are discussed. The book is of interest to biochemists and molecular biologists as well as to clinicians and the pharmaceutical industry who can apply the results in this field.

Where do you begin to look for a recent, authoritative article on the diagnosis or management of a particular malignancy? The few general oncology text­ books are generally out of date. Single papers in specialized journals are informative but seldom comprehensive; these are more often preliminary reports on a very limited number of patients. Certain general journals frequently publish good in-depth reviews of cancer topics, and published symposium lectures are often the best overviews available. Unfortunately, these reviews and supplements appear sporadically, and the reader can never be sure when a topic of special interest will be covered. Cancer Treatment and Research is a series of authoritative volumes that aim to meet this need. It is an attempt to establish a critical mass of oncology literature covering virtually all oncology topics, revised frequently to keep the coverage up to date, and easily available on a single library shelf or by a single personal subscription. We have approached the problem in the following fashion: first, by dividing the oncology literature into specific subdivisions such as lung cancer, geni­ tourinary cancer, pediatric oncology, etc.; and second, by asking eminent authorities in each of these areas to edit a volume on the specific topic on an annual or biannual basis. Each topic and tumor type is covered in a volume appearing frequently and predictably, discussing current diagnosis, staging, markers, all forms of treatment modalities,basic biology, and more.

With the publication of these proceedings from the Second Drug Discovery and Development Symposium, this forum has become the main mechanism for bringing together the principal groups involved in both discovering and developing new approaches to the treatment of cancer. This Second Symposium emphasized the types of materials being discovered and their therapeutic activity. This is especially evident in the natural product discovery programs, where unique and active structures are being identified. The major contributors to the meeting were the investigators participating in the National Cooperative (Natural Products) Drug Discovery Groups [NC(NP)DDG]. These groups reflect an association among researchers at universities or cancer centers, pharmaceutical companies and the National Cancer Institute. Their sources of materials are varied, reflecting chemical inventories of pharmaceutical companies, organic synthetic compounds from the laboratory, cytotoxics as well as biologics and their hybrids, and natural products obtained from plants, marine organisms and microorganisms. The models employed in the discovery systems vary from broadly cellular based to specific enzymes to defined cellular functions. Each of them is believed important to the malignant state and will allow for the discovery of compounds which will have efficacy in cancer therapy. The goal of the participants is both to discover new anticancer agents and to develop them as efficiently as possible into clinically useful additions to treatment. Of importance is the fact that there are a number of promising leads which will soon be moving into the clinic thereby testing the effectiveness of this NC (NP) DDG approach.

Recent experimental evidence has made it increasingly clear In particular, this volume reviews the discrete steps involved that the properties of invasive, malignant cells during tumor in metastatic invasion: the interaction of invasive tumor cells development substantially impact on the host. This is under­ with extracellular matrices, the basement membrane, attach­ scored by a variety of biochemical properties of tumor cells ment to extracellular matrices, local proteolytic degradation during their differentiation and metastatic dissemination. of matrices, and the locomotion of invasive tumor cells These properties can be analyzed at different stages of tumor through such areas of localized degradation. The critical growth and progression and this volume explores the role of the cell surface in secondary tumor formation is characteristics of primary tumors as well as the shared reviewed as are important advances in the molecular biology characteristics of both primary and secondary tumors. of metastasis initiation and maintenance. Recent advances The primary tumor comes into existence following in the role of DNA methylation in the generation of tumor preneoplastic biochemical and cellular events that ultimate­ cell heterogeneity and tumor progression are also critically ly result in malignant transformation. Various aspects of summarized. Chapters in this volume also review molecular metabolism, predetermined by nutritional status, often play aspects of metastatic progression, and the use of the tech­ a basic role. Obesity, for example, is cancer-promoting. Cell nologies of DNA transfection and somatic cell fusion in the surface carbohydrates, cytoskeletal proteins, glycoproteins, exploration of molecular aspects of metastatic progression.

Tamoxifen has persisted as a widely accepted and administered drug for almost 25 years. Following the many scientific papers and books on the subject, it has remained a very intriguing substance. This, perhaps, is the reason for another monograph on Tamoxifen. It is regrettably true that overviews, even when up to date after exhaustive research - the shibboleth of our cultures -, rapidly lose relevance with the passage of time. Scientists can sometimes be pictured as deep sea divers, who plunge into the unknown in search of a hitherto unknown world. Their descent is exciting, but eventually they must come up for air and integrate their experiences with others who also had to resurface. This book intends to collect and, where possible, to collate recent, but sometimes seemingly unrelated information. To quote Stephane Mallarme:'Everything in the world exists to end up in a book'. Even if this is a tad cynical, it might not be far from the truth. If a little knowledge is a dangerous commodity, one can also add - tongue in cheek - that a vast amount of knowledge can be truly hazardous. It is likely that what might seem as entangled data is confusing, especially for those satisfied with the comfortable interpretation of Tamoxifen as an antiestrogen which has long been found insufficient. The complexity of its mechanisms and effects defies simple explanations and may even seem capricious, but only because of our ignorance.

How is growth controlled in normal cells? How are the growth control mechanisms perturbed in cancer cells? This book provides an up-to-date description of research aimed at resolving these questions. It is organized into four sections, each containing a series of short reviews written by experts in the field. The general headings are: growth factors, receptors, and related oncogenes: transduction of mitogenic signals and ras oncogenes; nuclear oncogenes and regulation of gene expression; and multiple steps involved in malignant transformation. The articles emphasize concepts rather than detailed facts and are intended not only for specialists in the field but also for interested readers, such as physicians and advanced students, who wish to stay abreast of developments in one of the most exciting fields in current biomedical research.

Calcium-Sensing Receptor provides an overview of various aspects of the calcium receptor's biochemistry, physiology and pathophysiology that is suitable both for those who have been working in the field of Ca2+0-sensing as well as those who are new to this discipline. Calcium-Sensing Receptor is the nineteenth volume published in the Endocrine Updates book series under the Series Editorship of Shlomo Melmed, MD.

As in CANCER CHEMOTHERAPY 1, this volume brings to the reader highlights in three different areas of cancer therapeutics: new concepts and models; drug classes; and clinical settings. Topics were chosen because of their timeliness or probable current impact in cancer treatment. Authors were selected on the basis of their ability to provide a critical overview of specific subjects and their involvement in original work. I shall review the aims of this second volume, and then elaborate on the scope of its con­ tents. The principal aim of the volumes on cancer chemotherapy in the'Cancer Treatment and Research'series, as stated in the preface to the first volume, is to assemble in a concentrated form selected ingredients of chemothera­ peutic progress. These ingredients are to include concepts in therapeutic strategy, pre-clinical studies, development of major classes of compounds, identificatlon of new directions and of landmarks of clinical progress. Thus we do not foresee overlap with series which provide an yearly update of chemotherapy in an encyclopedic manner, or reviews of cancer chemother­ apy. Unlike those publications, our volumes are not intended to seek a place in shelves as a reference manual. It is this Editor's hope that persons repre­ senting various biomedical disciplines will seek the'Cancer Treatment and Research'chemotherapy volumes to survey advances in the field at regular intervals.

In Breast Cancer: Cellular and Molecular Biology [Kluwer Academic Pub­ lishers, 1988], we tried to present an introduction to the emerging basic studies on steroid receptors, oncogenes, and growth factors in the regulation of normal and malignant mammary epithelium. The response to this volume was superb, indicating a tremendous interest in basic growth regulatory mechanisms governing breast cancer and controlling its malignant progres­ sion. In the two years since its publication, much new and exciting in­ formation has been published and the full interplay of regulatory mechanisms is now beginning to emerge. We have divided this book into four sections that we hope will unify important concepts and help to crystallize areas of consensus and/or disagreement among a diverse group of basic and clinical scientists working on the disease. The first section is devoted to studies on oncogenes, antioncogenes, proliferation, and tumor prognosis. The first chapter, by Sunderland and McGuire, introduces the characteristics of breast cancer as studied by patho­ logists to establish prognostic outcome. Of particular interest is a new proto­ oncogene called HER-2 (or neu), which is rapidly becoming accepted as a valuable new tumor marker of poor prognosis. The second chapter, by Lee Bookstein and Lee, introduces the best known antioncogene, the retinoblas­ toma antioncogene, whose expression is sometimes lost in breast cancer. Malignant progression appears to be influenced by the balance of proto­ oncogene and antioncogene expression.

In our environmentally conscious society, reports of an increase in the risk of developing several cancers - including melanoma, lymphoma and lung cancer - have excited great controversy. Of these tumors, melanoma has demonstrated the most spectacular increase, generating a considerable body of research. The justification for this volume is found in the need for an up-to-date review of this research. The book represents a comprehensive review of both current research and clinical management of melanoma, arranged in such a way as to be maximally user-friendly to both the basic scientst and the clinician interested in this fascinating disease.

The study of tumour resistance to anticancer drugs has been the subject of many publications since the initial discovery of the phenomenon by J. H. Burchenal and colleagues in 1950. Many papers have been published since then reporting development of resistance to most of the well-known anticancer agents in many different animal tumour systems, both in vivo and in vitro. Many different mechanisms of resistance have been described, and it is clear that the tumour cell has a wide diversity of options in overcoming the cell-killing activity of these agents. Definition of the magnitude of the phenomenon in the clinic is, however, much more problematical, and it is with this in mind that the initial chapter, seeks to out­ line the problem as the clinicians see it. It appears that the phenomenon of true resistance to a drug, as the biochemist would recognise it, is an important cause of the failure which clinicians experience in treating the disease. The extent of the contribution of this phenomenon to the failure of treatment cannot easily be evaluated at the present time, but it is hoped that the development and application of new and more sophisticated techniques for the analysis of cellular sub­ populations may help to give a more exact estimate and to shed some light on the causes of failure of many of the present therapeutic techniques.

This volume presents a current review of the multimodal treatment of rectal carcinoma given today. Therapeutic concepts are developed and discussed with respect to experience gained from the most recent clinical studies and the results of molecular biology and genetics and clinically oriented research. Hence, the reader is given the opportunity to become informed of new research-related insights and their pracitical effect and implementation. The book contains chapters on molecular biology, staging, surgical treatment - with special emphasis on sphincter preservation - options for treating recurrent tumors and aftercare based on present knowledge, all of which have been written by international experts in their respective fields.

I have been privileged to witness and participate in the great growth of knowledge on chemical carcinogenesis and mutagenesis since 1939 when I entered graduate school in biochemistry at the University of Wisconsin­ Madison. I immediately started to work with the carcinogenic aminoazo dyes un­ der the direction of Professor CARL BAUMANN. In 1942 I joined a fellow graduate student, ELIZABETH CA VERT, in marriage and we soon commenced a joyous part­ nership in research on chemical carcinogenesis at the McArdle Laboratory for Cancer Research in the University of Wisconsin Medical School in Madison. This collaboration lasted 45 years. I am very grateful that this volume is dedi­ cated to the memory of Elizabeth. The important and varied topics that are reviewed here attest to the continued growth of the fields of chemical car­ cinogenesis and mutagenesis, including their recent and fruitful union with viral oncology. I feel very optimistic about the application of knowledge in these fields to the eventual solution of numerous problems, including the detection and estimation of the risks to humans of environmental chemical carcinogens and re­ lated factors.

Why have another book in the bone-calcium field? When the idea was first raised that this important area of biomedical research should be given more attention in the review literature, we felt that comprehensive texts recently published and in press were directed at more general audiences and did not address in detail some of the important areas of current investigation. As this field has grown and matured, information has accumulated at such a rapid rate that it has become impossible to keep abreast of all areas by reading the original articles in the scientific literature. Accordingly, we believed there was a void which could be filled by a collection of essays on specific topics in which significant progress had recently been made. Thus, this book is meant to be an up-to-date account of specific topics by investi­ gators at the forefront of their areas of research. We have tried to review major areas of basic science in the field which have an impact on our understanding of the diseases of bone and mineral. We hope that you will agree that the authors have done an outstanding job, and will find the volume as stimulating to read as we have. San Antonio, TX, USA GREGORY R. MUNDY Melbourne, Australia T. JOHN MARTIN Spring 1993 Contents CHAPTER 1 Calcium Homeostasis A. M. PARFITI. With 12 Figures 1 A. Introduction and Scope..................................... 1 B. Concepts of Homeostasis................................... 3 C. Extracellular Fluid Free Calcium: The Controlled Variable......

F. M. MUGGIA When faced with the inadequacies of current cancer treatment, we prefer to look at what the future may hold. Quite often, we take for granted the past, preferring research into totally new areas. However, the persistent development of fertile soil may yield surprising rewards for those who choose to build on the knowledge of the past--hence, this symposium on anthracycline antibiotics. Although the anthracycline antibiotics represent much of the present and future of cancer treatment, their actual use c stretches back barely two decades to the pioneering efforts of Aurelio Di Marco, who characterized the antitumor properties of daunomycin and adriamycin. • The clinical application of these two compounds heralded a decade of excitement among oncologists dealing with pediatric tumors, breast cancer, leukemias, and lymphomas, and opened new hope for patients afflicted with sar­ comas and a variety of other tumors that had been deemed - sistant to chemotherapy. These successes were tempered with the realization that the antitumor effect of anthracyclines could be achieved at times only at the very high price of risking cardiac decompensation and, almost invariably, with the occurrence of alopecia and other acute toxicities. This record of past achievements and problems has slowly given way to a present increasingly illuminated by our ability to modify the distressing toxicities of these agents. Detailed clinical studies supplemented by ingenious laboratory models have gradually elucidated mechanisms and risk factors im­ plicated in the cardiomyopathy.

This two-volume treatise, the collected effort of more than 50 authors, represents the first comprehensive survey of the chemistry and biology of the set of molecules known as peptide growth factors. Although there have been many symposia on this topic, and numerous publications of reviews dealing with selected subsets of growth factors, the entire field has never been covered in a single treatise. It is essential to do this at the present time, as the number of journal articles on peptide growth factors now makes it almost impossible for anyone person to stay informed on this subject by reading the primary literature. At the same time it is becoming increasingly apparent that these substances are of universal importance in biology and medicine and that the original classification of these molecules, based on the laboratory setting of their discovery, as'growth factors,''lymphokines,''cytokines,'or'colony­ stimulating factors,'was quite artifactual; they are in fact the basis of a com­ mon language for intercellular communication. As a set they affect essentially every cell in the body, and in this regard they provide the basis to develop a unified science of cell biology, germane to all of biomedical research. This treatise is divided into four main sections. After three introductory chapters, its principal focus is the detailed description of each of the major peptide growth factors in 26 individual chapters.

The concept that hormones influence tumor growth originated in 1889 with the proposal of Albert Schinzinger who suggested that breast cancer is related to the ovaries. Several years later, Sir George Beatson observed that remission of disseminated breast cancer could be achieved in premenopausal patients by performing bilateral oophorectomy. As a result of the contri­ butions of Hedley Atkins, Charles Huggins and others, additive and ablative hormonal therapies have been widely used for the treatment of advanced breast cancers for several decades. Model systems to study the effects of hormones on growth and regression of breast tumors have been available for many years; however, the complexities of the hormonal environment have rendered in vivo studies difficult in man and experimental animals. Recently, the availability of long-term cultures of breast cancer cells has stimulated many investigators to use these cell lines to unravel the mechanisms of hormone action. Because of the extreme diversity and complexity of advances regarding the endocrinology of the breast and breast cancers, a multi-authored review was deemed necessary. It has been gratifying to receive contributions from many noted scholars. In Volume I of this monograph, the influence of steroid hormones and their antagonists upon normal and neoplastic tissues of the mammary gland are presented. In Volume II, the effects of peptide and other hormones are reviewed.

The European School of Oncology came into existence to respond to a need for information, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons }Vhy such an initiative was considered necessary. Firstly, the teaching of oncology requires a rigorously multidisciplinary approach which is difficult for the Universities to put into practice since their system is mainly disciplinary orientated. Secondly, the rate of technological development that impinges on the diagnosis and treatment of cancer has been so rapid that it is not an easy task for medical faculties to adapt their curricula flexibly. With its residential courses for organ pathologies and the seminars on new techniques (laser, monoclonal antibodies, imaging techniques etc.) or on the principal therapeutic controversies (conservative or mutilating surgery, primary or adjuvant chemotherapy, radiotherapy alone or integrated), it is the ambition of the European School of Oncology to fill a cultural and scientific gap and, thereby, create a bridge between the University and Industry and between these two and daily medical practice. One of the more recent initiatives of ESO has been the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on future developments in specific fields of oncology.

In 1925, J. B. Collip (1925) reported that extracts of parathyroid gland contained an activity that raised calcium levels in the blood of parathyroidectomized animals, and suggested that this was due to a hormone produced in the parathyroid gland. The story of parathyroid hormone discovery was indicative of ever-increasing sophistication in sample preparation and protein isolation techniques. This paper resolved earlier controversies over the function of the parathyroid glands and c- trol of blood calcium. The year 1961 was a banner year for parathyroid research, in which the peptides parathyroid hormone and calcitonin were purified, and in which it was suggested that calcitonin could lower blood calcium (Copp and Cameron 1961). In 1982 it was discovered that in neurons the primary RNA transcript for calcitonin could be alternatively-spliced to give calcitonin gene-reated peptide (CGRP), and shortly thereafter amylin (previously named islet amyloid polyp- tide, IAPP) was identified and shown to have homology to CGRP. Since then a and b CGRP have been delineated and adrenomedullin and intermedin discovered, and this family of homologous peptides has emerged. This family of peptide hormones has a diverse and constantly expanding range of important physiologic functions, including regulation of blood calcium, vascular tension, feeding behavior and pain recognition.

The sequencing of the human genome has brought human genetics into a new era of study resulting in the generation of an explosive amount of information. Application of genomic, proteomic, and bioinformatics technologies to the study of human genetics has made it possible for human genetic diseases to be studied on an unprecedented scale, both in silico and in the wet lab. This volume provides up-to-date coverage of the broad range of research topics in this fascinating area. In the first part of the book, a whole spectrum of approaches to human genetics research is reviewed for both background and the latest progress. In the second, important topics related to genetic research of various complex human diseases are discussed. The robust content and diverse array of subjects allow the book to serve as both a concise “encyclopedia” that introduces basic and essential concepts of human genetics and an in-depth review of the current understanding of genetic research in human diseases.

A state-of-the-art review of the molecular underpinnings of bone-seeking cancers, current treatment approaches for them, and future therapeutic strategies. The authors illuminate the role of various autocrine, paracrine, and immunological factors involved in the progression and establishment of bone metastases, highlighting the physiological processes that lead to bone degradation, pain, angiogenesis, and dysregulation of bone turnover. They also discuss the various strategies that appear to have promise and are currently deployed in treatment or are at the experimental stage.

Any book under this title which creates both anticipation and anxiety must be the work of a lot of people, present any new findings with objectivity and cover the subject as exhaustively as possible. As such, it must cover the possible reproducible mechanisms of action/reaction EMF-Biological Organism, the appropriate models that allow quantitative measurements, the basic biological reproducible effects and possible therapeutic effects along with their prevalent metrics and international exposure criteria. This is exactly the main objective of this book. It is also believed that it provides some new results and conclusions which complement, clarify and verify the existing results in the literature included in the references [1] and [2]. Electromagnetic Radiation is a form of energy, which is transmitted in the form of waves which correspond to spatial and time variations of the electric and magnetic field. Electromagnetic fields appear in a vast set of frequencies (spectra) that are divided in frequency zones, according to the manner they are produced or used. Areas greater than 300 gigacycles (GHz), which include the solar spectrum, as well as x and gamma rays, have been studied sufficiently under a different angle in relation to possible biological effects. People are well aware of the harmful effects of sun radiation when they are exposed to the sunlight for extended periods of time and of the catastrophic effects of nuclear bombs and nuclear reactor leaks.

Over the past several years, there has been an extraordinarily rapid growth in our knowledge of oxidative stress and its possible involvement in both normal essential biology and digestive diseases. Oxidative stress is defined as a disturbance in the prooxidant-antioxidant balance in favor of the former, and has been suggested as a causative factor in inflammation, ischemia and carcinogenesis in the digestive organs. In the 1980s, biochemists and biologists were attracted by the role of reactive oxygen species in the irreversible damage or modification of the structure of biological molecules. However, in the 1990s, reactive oxygen species have been recognized to be involved in reversible structural alterations of molecules: The homeostatic modulation of oxidant levels is a highly efficient mechanism that allows all cells to tightly control their redox status within a very narrow range. Especially the activity of the Rel/NF-kB family of transcriptional factors that regulate responses in inflammation, reperfusion injury and apoptosis is controlled by intracellular reactive oxygen species levels. Our understanding of how these transcriptional factors are negatively or positively regulated by oxidative stress has since greatly increased. Questions for future investigation center on the modulation of oxidative stress by personal genome information for the prevention of several pathologic states.

Apoptosis or programmed cell death is increasingly considered to be a major factor in the development and progression of cardiovascular disease. In patients with heart failure the activation of apoptosis may result in the loss of irreplaceable cardiac myocytes promoting the clinical course of the syndrome. Moreover, in the coronary arteries inflammation and apoptosis may weaken critical structures of the vessel wall leading to plaque rupture and, subsequently, to myocardial infarction. Given these deleterious consequences, it seems almost paradoxical that programmed cell death is an active process that, if initiated under physiological circumstances, is essential for both coordinated tissue growth or destruction of malignant cells. Apoptosis in Cardiac Biology, written by a team of internationally renowned researchers, gives a timely synopsis of basic mechanisms, cellular and structural targets and, finally, clinical implications of programmed cell death in the heart. The expert authors of this volume give concise overviews on general and cell-specific aspects of programmed cell death in cardiac myocytes and fibroblasts, as well as in vascular smooth muscle and endothelial cells. Furthermore, novel therapeutic options arising from the outstanding pathophysiological significance of cardiac apoptosis are presented. This comprehensive review of Apoptosis in Cardiac Biology will be of interest to both clinicians and basic researchers who are active in the fields of cardiology and atherosclerosis.

This timely new reference integrates the latest clinical results and laboratory studies on the resistance of specific cancers to chemotherapeutic drugs-covering drug resistance in lung, breast, ovary, and colon cancer as well as hematological malignancies.