Lung cancer remains an extremely difficult neoplasm to treat effectively. A large part of our lack of success in dealing with these patients is related to our empiric therapeutic attempts. Slowly our basic understanding of the lung cancers is improving and techniques are becoming available to allow us to better understand the biology of these neoplasms. This volume reviews several areas of interest in regard to the biologic behavior and characteris of lung cancer. tics Chapters deal with the in vitro growth of small cell lung cancer, the inves tigation of growth factors in human lung cancer, the production of mono clonal antibodies against lung cancer and the application and potential use fulness of the human tumor cloning assay in lung cancer management. These avenues of investigation are likely to establish a more scientific basis on which more rational therapy can be designed. Carney and associates have established several continuous small cell lung cancer cell lines in their laboratory. The amine precursor uptake and decar boxylation (APUD) properties of this neoplasm have been confirmed by demonstrating the presence of neurosecretory granules and high levels of the APUD enzyme L-dopa decarboxylase. In addition, several new markers have been documented including bombesin, creatine-kinase BB and neuron specific enolase. These tumor products along with others may be useful serum markers in patients with small cell lung cancer."

Clinical and pathological observations have unequivocally indicated an increase in the incidence of malignant neoplasia during the last two decades. Despite important advances in surgery, radiotherapy and chemotherapy, mortality from tumours still tends to increase. Cancer research has therefore concentrated not only on early diagnosis and therapy but also, in line with recent trends in medical science, on the prevention of oncogenesis. One effi- cient prophylactic approach is the treatment of preblastomatoses, which include the preneoplastic lesions of the mouth. The most frequent oral pre- cancerosis, leukoplakia, has been studied extensively during the last 20 years with regard to its pathogenesis,clinical course,and response to therapy. In Hungary, studies of oral leukoplakia have a century-long tradition. The term leukoplakia was coined by the Hungarian dermatologist Ern/) Schwimmer who recognized the precancerous nature of the condition and its relationship to tobacco smoking exactly 100 years ago. In the middle of this century another Hungarian scientist, Karoly Balogh established that most leukoplakias have two stages, - reversible and irreversible - and that early lesions may heal spontaneously after the elimination of irritational factors. The incidence of leukoplakia in random population groups was determined for the first time in the world by the Hungarian investigator Pal Bruszt, and reported to be 3.6 %. Subsequent studies in other countries confirmed a range of 0.2-8.1 %, depending on geographical and environ- mental conditions, way of life, and relevant habits.

The knowledge of Th17 cells and other cell populations which secrete IL-17A, and/or IL-22 has expanded tremendously since the publication of the first edition "Th17 Cells: Role in Inflammation and Autoimmune Disease" in 2008. The present volume has been completely revised with the addition of new chapters on the IL-17 receptor family and signaling, and an in-depth review of IL-22 and innate lymphoid cells. The differentiation of na ve T cells into regulatory T cells and Th17 cells as well as the plasticity of Th17 cells is discussed. The role of IL-22 in cutaneous inflammation including psoriasis has been reviewed. In addition, the volume contains critical updates on autoimmunity, organ transplantation, tumor immunology and genetic mouse models for mechanistic studies. Lastly, the latest clinical progress in neutralizing antibodies to IL-17A, IL-17RA not only confirms the therapeutic promise foreseen in 2008, but also improves our knowledge of the pathogenesis of autoimmune diseases. In summary, this is a timely update and important review of the clinical and experimental aspects of IL-17, IL-22 and their producing cells.

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.

Leading experts summarize and synthesize the latest discoveries concerning the changes that occur in tumor cells as they develop resistance to anticancer drugs, and suggest new approaches to preventing and overcoming it. The authors review physiological resistance based upon tumor architecture, cellular resistance based on drug transport, epigenetic changes that neutralize or bypass drug cytotoxicity, and genetic changes that alter drug target molecules by decreasing or eliminating drug binding and efficacy. Highlights include new insights into resistance to antiangiogenic therapies, oncogenes and tumor suppressor genes in therapeutic resistance, cancer stem cells, and the development of more effective therapies. There are also new findings on tumor immune escape mechanisms, gene amplification in drug resistance, the molecular determinants of multidrug resistance, and resistance to taxanes and Herceptin.

New and exciting biological functions are still being discovered for vitamin A derivatives, including the vast number of physiological activities of retinoids. In Retinoids: Methods and Protocols, expert researchers in the field present the most recent technical tools with diverse techniques for both in vitro and in vivo studies. Combining biochemical, biophysical, and cell biological techniques, the book addresses topics such as the detection and quantitation of retinoids using HPLC, mass spectrometry, and fluorescence, fluorescence anisotropy of retinol binding protein, cell culture models for studying retinoid transport and the role of retinol in embryonic stem cell culture, as well as many other detailed procedures. Written in the highly successful Methods in Molecular Biology(TM) series format, chapters include introductions to their respective subjects, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes highlighting tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Retinoids: Methods and Protocols seeks to aid beginning and experienced researchers from widely varied fields in the search to uncover even more vital aspects of vitamin A's impact on the human body.

This book highlights recent progress in the molecular, cellular and immunological mechanisms that contribute to the pathophysiology of cancer and the design of therapeutic modalities based upon these molecular insights. Areas of particular emphasis include cancer immunology and the immunotherapy of cancer, the role of cytokines in modulating the social bahaviour of cancer cells, the genetic alterations that characterize human cancer and metastasis, and a consideration of the more experimental approaches to cancer therapy, including gene therapy using expression vectors for cytokines and their receptors, antisense RNA therapy, and anti-idiotypic antibody immunization. This volume serves to introduce the general reader as well as the cancer specialist to personalized perspectives of particular topics in cancer research by leading research groups in the field. The combination of a ''reviews''-approach with a more research-oriented approach in discussions of specific research topics provides a stimulating and, hopefully, forward-looking volume which serves to update selected aspects of cancer research today. This combination will be useful to both the beginner as well as the more advanced biomedical scientist.

This is a comprehensive, state-of-the-art guide to the diagnosis, treatment, and biology of multiple myeloma and related plasma disorders. Edited and written by a multidisciplinary group of recognized authorities from the Mayo Clinic, it presents clear guidelines on diagnosis and therapy and covers all aspects of multiple myeloma, from molecular classification and diagnosis, to risk stratification and therapy. Closely related plasma cell disorders such as solitary plasmacytoma, Waldenstrom macroglobulinemia, and light chain amyloidosis are discussed in detail as well. The book addresses often overlooked topics, including the role of radiation therapy, vertebral augmentation, and supportive care. Our understanding of this group of disorders is developing at an unprecedented rate, and Multiple Myeloma meets the need among oncologists and hematologists for a clear, timely, and authoritative resource on their biology, diagnosis, and treatment.

One of the main causes of failure in the treatment of breast cancer is the intrinsic presence of, or development of, drug resistance by the cancer cells. Recent studies on the mechanisms of cancer drug resistance have yielded important information highlighting both how tumour cells may escape these therapeutic constraints and that drug resistance may further impinge on tumour cell functions that may ultimately promote an adverse cell phenotype. New targets have been identified with potential therapeutic applications in resistant breast cancer leading to the subsequent evaluation of inhibitors of these targets in preclinical studies. Importantly, there is increasing evidence from such studies demonstrating the benefit of novel combination strategies as potential avenues for future drug regimens.

Written by experts in the subject area, this book covers the molecular details and functional consequences of endocrine resistance in breast cancer with particular emphasis on the future applications of novel drug combinations that may be utilized to circumvent resistance and improve anti-tumour effects. This book represents a timely publication in the field of breast cancer research, providing current knowledge in the area of drug resistance and will be important reading material for clinicians and researchers alike.

Lipid peroxidation is an important cellular process which can lead to detrimental effects if it is not regulated efficiently. Lipid hydroperoxide is formed in an initial step of lipid peroxidation. Lipid hydroperoxide is also known as a potential source of singlet oxygen. Harmful aldehydes are formed when the lipid hydroperoxide is degraded. The formed aldehyde has high reactivity against thiol or amine moieties. Therefore, it could act as a signaling molecule, which might induce the changing of gears inside a cell. Recent studies have shown that lipid hydroperoxide or a slightly modified product of the lipid hydroperoxide reacts with biomolecules such as proteins and aminophospholipids, which leads to formation of amide-type adducts. Amide-type adducts could be one of markers for oxidative stress and could also be an important player in some diseases. In this book, the chemistry and biochemistry of lipid hydroperoxide along with their conjugates with biomolecules are described.

Inappropriate activation of the Wnt signaling pathway is observed in many human cancers and is sufficient to drive tumor initiation and progression in numerous contexts. Multiple mechanisms, such as overexpression of Wnt ligands, inactivation of the APC and Axin tumor suppressors, and mutation of -catenin, are responsible for pathway activation in tumor cells. The development of potent Wnt pathway antagonists for therapeutic use has been a major effort for investigators in both academia and industry in recent years. This book will provide an overview of the Wnt pathway as a therapeutic target for cancer, and discuss the preclinical development of inhibitors specifically directed to upstream and downstream components of the pathway.

The field of pediatric oncology encompasses four groups of malignancies - acute leukemias, brain tumors, lymphomas and solid tumors. 1'he history, diagnosis and management of children with acute leukemias and lymphomas has been thoroughly examined in several excellent textbooks of pediatric hematology and oncology. Bl"ain tumors have historically been managed by neurosurgeons and radiation therapists. 1'he role of the pediatric oncologist in the management of these patients is evolving. This book was written to provide a thorough historical evaluation of the most frequent solid tumors of children. A detailed examination of the natural history of these tumors is essential to the design and evaluation of therapeutic trials. The highly lethal nature of many of these tumors, the occurrence of some of them at several different primary sites and the rarity of these tumors have made systematic study of them difficult. Conclusions regarding the efficacy of a particular modification of the therapeutic strategy can be strongly influenced by the assumed natural history of the tumor. I have tried to develop as accurateJy as the literature would allow a picture of the natural history of the common malignant solid tumors, knowing that the image would be imperfect. I adopted a convention which was employed in all graphs constructeil from case reports summarized from the literature.

This book is a comprehensive and up-to-date compendium on all aspects of blood and marrow transplantation in children. After an introductory chapter describing the history of pediatric blood and marrow transplantation, subsequent chapters discuss pediatric-specific aspects of transplantation, including stem cell sources suitable for transplantation, preparative regimens, graft-versus-host disease, complications related to transplantation, and late effects. The role of blood and marrow transplantation in various specific pediatric diseases is then examined, and the closing chapter considers future directions. The authors are all internationally recognized experts and offer a largely evidence-based consensus on etiology, biology, and treatment. This handbook has far-reaching applicability to the clinical diagnosis and management of pediatric diseases that are treatable with blood and marrow transplantation and will prove invaluable to specialists, generalists, and trainees alike.

This volume of Molecular Biology of Hematopoiesis is dedicated to many inter national scientists and clinicians for their contribution to the field of Hematology/ Oncology presented at the 11th International Symposium on Molecular Biology of Hematopoiesis, which was held in Bormio, Italy, June 25-29, 1998. The continuous support of the Presidents of the meeting, Professor F. Takaku, President of Jichi University, and E. D. Thomas, Nobel Laureate, was greatly acknowledged, especially Professor Takaku, for his vision and support for development of gene therapy in Japan. New information on BMT for autoimmune disease and organ transplantation was presented at the symposium and is published in this volume. Several new findings on gene therapy/transfer into HSC were presented by E. F. Vanin and A. Nienhuis, K. Humphries, 1. A. Nolta, H. E. Heslop, and M. K. Brenner. Professors S. Asano and K. Tani presented new studies on gene transfer into primates. Among the highlights were the new papers on gene transfer presented by G. Wage maker, N. G. Abraham, and M. Onoderea from R. M. BJaese's group. The use of BMT for organ transplant and autoim mune disease was updated and a representative paper is presented in this volume.

Breast Imaging presents a comprehensive review of the subject matter commonly encountered by practicing radiologists and radiology residents in training. This volume includes succinct overviews of breast cancer epidemiology, screening, staging, and treatment; overviews of all imaging modalities including mammography, tomosynthesis, ultrasound, and MRI; step-by-step approaches for image-guided breast interventions; and high-yield chapters organized by specific imaging finding seen on mammography, tomosynthesis, ultrasound, and MRI. Part of the Rotations in Radiology series, this book offers a guided approach to breast imaging interpretation and techniques, highlighting the nuances necessary to arrive at the best diagnosis and management. Each chapter contains a targeted discussion of an imaging finding which reviews the anatomy and physiology, distinguishing features, imaging techniques, differential diagnosis, clinical issues, key points, and further reading. Breast Imaging is a must-read for residents and practicing radiologists seeking a foundation for the essential knowledge base in breast imaging.

Blood Cell Biochemistry was initially conceived as part of the Plenum series Subcellular Biochemistry, from which it has developed into a separate series. The present volume is devoted primarily to contributions on megakaryocytes and platelets and, to a lesser extent, to macrophages and eosinophils. The book does not attempt a rigorous or total coverage of the particular topics; it represents the areas of current scientific activity and interest that were selected by the editor at the commencement of this project. In general, the approach has been similar to that adopted for Volume 1 of the series (Erythroid Cells); the same approach will be followed subsequently in Volume 3 (Lymphocytes and Granulocytes). This book opens with a developmentally oriented chapter by Janine Breton-Gorius on megakaryocyte maturation and platelet release in normal conditions, which serves to set the scene ultrastructurally for much of the data that follow. The biosynthesis and process ing of platelet glycoproteins in megakaryocytes is dealt with by Alain Duperray and his colleagues, and thereby provides an in-depth biochemical survey of the megakaryocyte. The applications and strengths of crossed immunoelectrophoresis for the study of platelet membrane proteins is then covered by Simon Karpatkin, and a detailed account of the heredity disorders of platelet function is provided by Francine Rendu and Evelyne Dupuy."

This book presents in a comprehensive way cur the clinical care of the patient with head and neck rent advances in the management of neoplasia cancer involvement and/or its complications. and associated complications of the head and Today's complex treatments in oncology re neck. A broad range of clinical considerations is quire a comprehensive approach to effect a posi discussed following overviews of relevant basic tive result for the cancer patient whose facial biologic issues and the roles of various disci appearance and function are compromised. We plines. Each chapter has been structured to trust that physicians, dentists, nurses, dental "stand by itself"; at the same time, obvious rela hygienists, and individuals in the supportive ser tionships with other chapters have been noted. vices involved in the management of the cancer We are pleased that this book represents, in our patient will find this book beneficial. opinion, a truly multidisciplinary approach to Xl I. INTRODUCTION 1. CANCER, ITS COMPLICATIONS, AND THE HEAD AND NECK Stephen T. Sanis Few diseases are as complex in their biology, tumors, such as colorectal cancers, seems physiology, pathology, or management as can equivocal [3]. cer [1, 2]. In addition, the disease concurrently has extensive psychological impact on patients.

Humans are diurnal organisms whose biological clock and temporal organization depend on natural light/dark cycles. Changes in the photoperiod are a signal for seasonal acclimatization of physiological and immune systems as well as behavioral patterns. The invention of electrical light bulbs created more opportunities for work and leisure. However, exposure to artificial light at night (LAN) affects our biological clock, and suppresses pineal melatonin (MLT) production. Among its other properties, MLT is an antioncogenic agent, and therefore its suppression increases the risks of developing breast and prostate cancers (BC&PC). To the best of our knowledge, this book is the first to address the linkage between light pollution and BC&PC in humans. It explains several state-of-the-art theories, linking light pollution with BC&PC. It also illustrates research hypotheses about health effects of light pollution using the results of animal models and population-based studies.

Oncology has developed as a subspecialty of medicine with unique and often complex clinical problems. This handbook ofhematologic and oncologic emer gencies provides a compact, concise, yet comprehensive guide to the manage ment of a variety of difficult clinical situations. The authors of the various chapters are all clinicians with experience in the management of these difficult patients. Their efforts provide insight and a ready source of practical infor mation which lends itself to use in the clinic and in the inpatient ward. The authors sincerely hope that this handbook will be of service to house officers and fellows alike, as they develop skills in the management of the emergent problems of patients with hematologic and other neoplasms. Janice P. Dutcher Peter H. Wiernik Bronx, New York;; Contents 1. Syndrome of Inappropriate Antidiuretic Hormone Secretion and Hyponatremia . . . . . . . . . . . . . . . . . . . . . . . . 000 . . . . . . . . . . . Stuart L. Marcus, M.D., Ph.D., and Joachim Z. Fuks, M.D. 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 3. Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 4. Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 5. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2. Acute Tumor Lysis Syndrome: Prevention and Management . . 9 Stuart L. Marcus, M.D., Ph.D., and Avi I. Einz;ig, M.D. 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 2. Risk Factors for the Development of Azotemia in Acute Tumor Lysis Syndrome........................................... 10 3. Metabolic Abnormalities That Occur during Acute Tumor Lysis Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 . . . . . . . . . . . . . . 4. Prevention of Acute Tumor Lysis Syndrome: Management prior to Beginning Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . 13 . . . . . . . . . . 5. Posttreatment Management: Indications for Dialysis . . . . . . . . . . 14 . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 . . . . . . . . . . . . . ."

This volume explores the myriad of techniques and methodological approaches that are being used in breast cancer research. The authors critically evaluate of the advantages and disadvantages of current methodologies, starting with the tools available for understanding the architecture of the human breast, including its tissue and cellular composition. The volume discusses the importance of functional studies in breast cancer research, especially with the help of laser capture microdissection, which allows the separation of small amounts of tissue, as well as specific cells, for biochemical analysis. In addition, the authors address methodologies including stem cell separation, which has helped in significantly understanding their role in normal breast development, but also further the understanding of breast cancer and its therapeutic management. The use of in vitro techniques and established cell lines for mechanistic studies in chemotherapeutic approaches have been invaluable will be discussed. Imaging techniques for evaluating in vitro and in vivo behavior of normal and cancerous breast tissue will be explored, as it provides a better understanding of the physiopathology of cancer. The volume will also discuss the molecular analysis of gene function in breast cancer through the transcriptomic and epigenomic profile. More importantly, the advancement of more refined techniques in sequencing will be covered. This monograph will be a comprehensive, authoritative and timely, as it addresses the emerging approaches used in breast cancer research.

Defining the Lung Cancer Problem 1 Lung cancer is the leading cause of cancer death in the world. It kills almost as many Americans as cancers of the breast, prostate, colon, rectum, pancreas, and 2 kidney combined, and accounts for 28.6% of all US cancer deaths. With an increase in the 5-year relative survival rate from 13% to only 16% in the more than 2 30 years from 1974 to the present, it will take us another 840 years to eradicate lung cancer deaths if we do not improve the current rate of progress. As discussed in this text, lung cancer prevention has received substantial att- tion. The decrease in smoking in recent decades has helped, but smoking is not the only problem. Lung cancer in people who have never smoked is currently the 5th 3 leading cause of cancer death in the United States. Several factors contribute to the lethality of lung cancer, including the rapidity of tumor growth, advanced stage at diagnosis (due to nonspecificity of early sy- toms and the uncertain efficacy of screening), early development of metastases, and resistance to therapy. Several chapters in this book discuss new molecular targets that may be potentially exploitable in the future, as well as discussing our track record to date in exploiting them.

Providing a true integration of pathology with clinical management, this volume presents a practical, comprehensive text on benign and malignant disease of the adult bladder. Integrating pathology, surgical management, oncology and molecular study in a site-specific manner to include the urethra, urinary bladder, ureter and renal pelvis, The Urinary Tract: A Comprehensive Guide to Patient Diagnosis and Management is the first text in adult bladder disease to closely interweave multiple clinical disciplines into each chapter. For the majority of chapters, a pathologist and urologist or urologic oncologist are paired to provide the greatest integration of information for each disease process.