Over the last 50 years, drug development and clinical trials have resulted in successful complete responses in diseases such as childhood leukemia, testicular cancer and Hodgkin's disease. We are still, however, confronted with over 500,000 cancer-related deaths per year. Clearly, the phenomenon of drug resistance is largely responsible for these failures and continues to be an area of active investigation. Since the last volume in this series, we have learned that the energy-dependent drug efflux protein, p-glycoprotein, encoded by the MDR 1 gene, is a member of a family of structurally related transport polypeptides, thus allowing us to explore the relationship between structure and function. In addition to ongoing well designed clinical trials aimed at reversing MDR mediated drug resistance, the first gene therapy studies with the MDR 1 gene retrovirally transduced into human bone marrow cells are about to be initiated. Although MDR is currently the most understood mechanism of drug resistance, we are uncovering increasing knowledge of alternative molecular and biochemical mechanisms of drug resistance to antimetabolites, cisplatin and alkylating agents and developing new strategies for circumventing such resistance. It is clear that drug resistance is complex, and many mechanisms exist by which cancer cells may overcome the cytotoxicity of our known chemotherapeutic agents. As our understanding of each of these mechanisms expands, well designed models will be necessary to test laboratory hypotheses and determine their relationship to drug resistance in humans. It is this integration of basic science and clinical investigation that will both advance our scientific knowledge and result in the improvement of cancer therapy.

Interest in angiogenesis research remains strong in recent years and exciting new discoveries, about modulators of angiogenesis, their receptors, the transduction mechanisms and the angiogenic genes involved, have contributed to our present day understanding of this complex process. This knowledge has provided the basis and broadened the scope of angiogenesis - based therapy in oncology and many other clinical conditions. This monograph contains the contributions to the NATO Advanced Study Institute on "Angiogenesis: Models, Modulators and Clinical Applications," which was held in Rhodes, Greece, from June 20-30, 1997. This was the fourth of a series of NATO supported international meetings on Angiogenesis aiming to bring together basic scientists with clinicians to exchange ideas, disseminate new knowledge and discuss the present status and potential new directions in this fast moving area of biomedical research. The International Organising Committee that included Drs. E. Dejana, C Haudenschild, M. Hackel, H. Kleinman, P. Lelkes, M. Presta, P. Polverini, D. Thompson, has provided invaluable help with their insightful suggestions in the formulation of the scientific program for which I am grateful. I wish to thank all the participants for their enthusiastic participation and their complimentary comments on the success of the conference.

Clinical trials remain the most important vehicle for improving the care of cancer patients. This text presents the fundamental components and challenges involving clinical investigations. Leading experts discuss the critical issues covering the spectrum of important topics from planning to application. The book has a foreword by Samuel A. Wells, Jr., MD, Professor of Surgery, Duke University Medical Center, Durham, NC, former Director of the American College of Surgeons and Founder of the American College of Surgeons Oncology Group.

This book sheds light on how dysregulated organelle functions contribute to the pathology and progression of human diseases. To offer a broad perspective, they discuss basic, translational, and clinical aspects across scales, from molecules to cells, tissues and organisms. Rather than providing a comprehensive introduction to the field, the authors focus on recent advances in organelle research, with each chapter inviting readers to consider today's key questions in the respective field. This book reviews the endoplasmic reticulum, Golgi Appartus, Lysosomes and other membrane-enclosed organelles, demonstrating how their dysregulated function contributes to various pathologies. The chapters not only offer a platform for new perspectives but also stimulate further investigations. Given the translational nature of this subject, this book is a valuable resource for physiologists and clinicians alike. Chapter "Lipid Droplets in Cancer" is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

Clinical trials have two purposes -- to treat the patients in the trial, and to obtain information which increases our understanding of the disease and especially how patients respond to treatment. Statistical design provides a means to achieve both these aims, while statistical data analysis provides methods for extracting useful information from the trial data. Recent advances in statistical computing have enabled statisticians to implement very rapidly a broad array of methods which previously were either impractical or impossible. Biostatisticians are now able to provide much greater support to medical researchers working in both clinical and laboratory settings. As our collective toolkit of techniques for analyzing data has grown, it has become increasingly difficult for biostatisticians to keep up with all the developments in our own field. Recent Advances in Clinical Trial Design and Analysis brings together biostatisticians doing cutting-edge research and explains some of the more recent developments in biostatistics to clinicians and scientists who work in clinical trials.

This volume explores the evolution of bacterial cancer therapy and describes the modern techniques used in therapy today. The chapters in this book cover a broad range of topics such as the development of tumor-targeting Salmonella typhimurium A1-R, a microfluidic device for precise quantification of the interactions between tumor-targeting bacteria and tumor tissue, non-invasive in vivo imaging of bacteria-mediated cancer therapy using bio-luminescent bacteria, methods to achieve remote-control of therapeutic gene expression in tumor-targeting bacteria, and cell-cycle decoy of cancer cells resistant to cytotoxic drugs to drug sensitivity by S. typhimurium A1-R. This book concludes with a chapter on the future potential of bacterial therapy of cancer. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Thorough and informative, Bacterial Therapy of Cancer: Methods and Protocols is a valuable resource for anyone who is interested in cancer and bacterial therapy.

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.

This book covers all aspects of chronic radiation syndrome (CRS) based on observations in a unique sample of residents of the Techa riverside villages in the southern Urals who were exposed to radioactive contamination in the 1950s owing to releases of liquid radioactive wastes from Mayak Production Association, which produced plutonium for weapons. In total, 940 cases of CRS were diagnosed in this population and these patients were subjected to detailed analysis. The opening chapters address the definition and classification of CRS, epidemiology and pathogenesis, covering molecular and cellular mechanisms, radioadaptation, and the role of tissue reactions. The pathoanatomy of CRS during the development and recovery stages is discussed for all organ systems. Clinical manifestations of CRS at the different stages are then described in detail and the dynamics of hematopoietic changes are thoroughly examined. In the following chapters, principles of diagnosis (including assessment of the exposure doses to critical organs) and differential diagnosis from a wide range of other conditions are discussed and current and potential treatment options, described. The medical and social rehabilitation of persons with CRS is also covered. This book, which casts new light on the condition, will be of value for all practitioners and researchers with an interest in CRS.

Role of Tumor Microenvironment in Breast Cancer and Targeted Therapies discusses the current understanding of breast cancer tumor microenvironment components, their role in tumorigenicity and the development of therapeutic resistance, along with updates on recent advances.

Internationally recognized experts in cancer biology and clinical research review the present status of the multimodality approach to the management of solid tumors and speculate on possible future strategies for chemoradiation therapy. The authors detail applications of combined modality therapy in lung, esophageal, breast, gastric, pancreatic, colon, and rectal cancers. They also show how radiation interacts with such chemotherapeutic agents as the platinum complexes, taxanes, and gemcitabine in the treatment of malignant gliomas, and head and neck cancer. A review of how to integrate new specific molecular targeted agents into multimodality therapy in the future.

Cutting-edge researchers describe their efforts to design, synthesize, and evaluate the biological activities of farensyltransferase inhibitors (FTIs); geranylgeranyltransferase inhibitors (GGTIs) are also discussed as potential anticancer drugs. The authors survey in detail such inhibitors as CAAX box peptidomimetics, FPP mimics, and bisubstrate transition state analogs, and critically review their uses in combination with radiation and other cytotoxic agents, such as gemcitabine, cisplatin, and taxanes. Illuminating and richly detailed, Farnesyltransferase Inhibitors in Cancer Therapy constitutes today's standard reference for the pathbreaking use of FTIs and GGTIs in anticancer therapy and offers basic and clinical investigators a comprehensive treatment of the scientific and medical aspects of farnesyltransferase inhibitors.

Primary lung tumors are now a global health problem. The incidence has risen dramatically during the last 5--6 decades, reflecting the popularity of cigarette smoking. In this, the fifth volume dealing with lung cancer in the series KappaCANCER TREATMENT AND RESEARCHkappa, many current research topics are covered by notable authorities, including chemoprevention, growth factors, multidrug resistance, new agents, and haematopoietic growth factors. Altogether, the 17 chapters from twelve countries highlight some of the rapid developments taking place in basic and clinical research of lung cancer. These chapters not only give up-to-date information, they will also stimulate further research into this man-made disease which was almost unheard of a century ago.

Introduction of new technologies and their applications to neuroblastoma diagnosis, treatment, and therapy assessment are explained. Role of molecular ghenetics in diagnosis and therapy for neuroblastoma patients is detailed. Molecular detection of minimal residual neuroblastoma is described. Magnetic resonance imaging and spectroscopy are detailed for diagnosing this solid, extracranial cancer. Targets for therapeutic intervention in neuroblastoma are identified, including targeting multidrug resistance in this cancer. Ornithine decarboxylase and polyamines are novel targets for therapeutic intervention. The effectiveness of chemotherapy with oral irinotecan and temozolomide is explained. The role of transcription factors (GATA) in neuroblastoma pregression is also included.

This handbook is a concise, thorough, and portable reference guide to the multitude of complex chemotherapy protocols and other frequently utilized medications in the field of Hematology/Oncology. Its inclusion of commonly used oncology regimens, guidelines for supportive care during administration and sections on pain control, antibiotic use and antiemesis guidelines set it apart from other "chemotherapy handbooks". The authors have prepared this book with the intention of improving the care of those suffering from cancer.

Capsaicin is a principal pungent ingredient of red chili peppers, first isolated in the early nineteenth century by Christian Friedrich Bucholz. Widely consumed as a spice in South Asia and Latin America, Capsaicin has been used to treat pain and inflammation associated with a variety of diseases, including rheumatoid arthritis, diabetic neuropathy, post-masectomy pain, cluster headaches, and herpes zoster. Although recent studies have evaluated capsaicin as a novel anti-cancer agent, and mechanisms of capsaicin in preventing cancer have been described sporadically, the literature lacks a comprehensive review of capsaicin as a chemo-preventive agent. Role of Capsaicin in Oxidative Stress and Cancer offers a thorough exploration of the preventive and therapeutic effects of capsaicin in cancer models such as melanoma, pancreatic cancer, colon cancer, gastric cancer, breast cancer, prostate cancer, skin cancer, lung cancer, multiple myeloma and glioma. The contributors, all internationally recognized researchers, identify various molecular and cellular targets of capsaicin, and show the critical role of mitochondria in capsaicin-mediated therapeutic effects. Readers will learn how capsaicin prevents or may treat cancer, how different cells respond to capsaicin, how environmental carcinogen-induced carcinogenesis can be prevented by capsaicin and the mechanism of oxidative stress caused by capsaicin. This book will benefit medical students, oncologists and cancer researchers everywhere.

An integrated overview of cancer drug discovery and development from the bench to the clinic, showing with broad strokes and representative examples the drug development process as a network of linked components leading from the discovered target to the ultimate therapeutic product. Following a systems biology approach, the authors explain genomic databases and how to discover oncological targets from them, how then to advance from the gene and transcript to the level of protein biochemistry, how next to move from the chemical realm to that of the living cell and, ultimately, pursue animal modeling and clinical development. Emerging cancer therapeutics including Ritux an, Erbitux, Gleevec Herceptin, Avastin, ABX-EGF, Velcade, Kepivance, Iressa, Tarceva, and Zevalin are addressed. Highlights include cancer genomics, pharmacogenomics, transcriptomics, gene expression analysis, proteomic and enzymatic cancer profiling technologies, and cellular and animal approaches to cancer target validation.

Between 1990 and 1993, breast cancer activism became a significant political movement. The issue began to receive extensive media attention, and federal funding for breast cancer research jumped dramatically. Describing the origins of this surge in interest, Maureen Hogan Casamayou attributes it to the emergence of politically potent activism among breast cancer survivors and their supporters. Exploring the creation and development of the National Breast Cancer Coalition (NBCC), she shows how many of its key leaders were mobilized by their own traumatic experiences with the disease and its treatments.

Casamayou details the NBCC's meteoric rise and impressive lobbying efforts, explaining how -- in contrast to grassroots movements founded by dedicated individuals -- the coalition grew from the simultaneous efforts of a network of women who invested their time, energy, money, and professional skills in the fight for increased funding for breast cancer research. This multiple leadership -- or collective entrepreneurialism, says Casamayou -- was crucial to the NBCC's success framing the issue in the minds of the public and policymakers alike.

Cancer Informatics: Essential Technologies for Clinical Trials describes the National Cancer Institute¿s vision of a Cancer Informatics Infrastructure (CII). By exploiting the best that the Internet and information technology have to offer, the CII will facilitate clinical trials, for all who are involved, including the patient along with the myriad of health professionals involved in cancer trials. To bridge the chasm between discoveries and best clinical practices, the editors describe the CII and how it can function to expedite the clinical trial life cycle, facilitate faster and safer drug development, and make more appropriate treatment choices available to cancer patients. Presented in four comprehensive sections edited by leading experts, the book highlights: ¿ E-commerce ¿ Digital libraries ¿ Standards development ¿ Public health informatics ¿ Common data elements (CDEs) ¿ Clinical trials information systems ¿ Consumer education and support Cancer Informatics: Essential Technologies for Clinical Trials is an indispensable guide to clinical trials. Its contributors speak to oncologists and primary care physicians, as well as researchers, trial managers, administrators, informaticians, and consumers. Today, science is extending our knowledge of genes, proteins, and pathways, and pharmaceutical companies are developing more and more new therapies. In this rapidly changing world, the technologies that cancer informatics provides are essential to efforts to translate cancer research into cancer care, control, and, ultimately, prevention. John S. Silva, M.D., Center for Bioinformatics, National Cancer Institute Marion J. Ball, Ed.D., Vice President, Clinical Solutions, Healthlink, Inc.; Adjunct Professor, The Johns Hopkins University School of Nursing Christopher G. Chute, M.D., Dr.P.H., Professor of Medical Informatics, Head, Section of Medical Information Resources, Mayo Clinic Judith V. Douglas, M.A., M.H.S., formerly Associate, First Consulting Group Curtis P. Langlotz, M.D., Ph.D., Assistant Professor of Radiology, Epidemiology, and Computer and Information Science, University of Pennsylvannia Joyce. C. Niland, Ph.D., Chair, Division of Information Sciences, Director, Department of Biostatistics, City of Hope National Medical Center William L. Scherlis, Ph.D., Principal Research Scientist, School of Computer Science, Carnegie Mellon University

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

This book discusses the mechanisms leading to immune-mediated tissue rejection following the hypothesis that independent of the disease process the final effector mechanism is shared by most (but not all) pathologies and it is relatively simple. The book covers evidence gathered to support the thesis by studies performed in humans during rejection or in experimental models and will focus particularly (but not exclusively) on the analysis of the rejected tissue rather than the systemic circulation. Several disease processes are discussed including example of chronic inflammatory process without resolution of the pathologic process and acute one with resolution of the pathologic process (clearance of pathogen, rejection of tumor) or unwanted tissue destruction (allograft rejection, autoimmunity).

While many books are available on disaster medicine, none is specifically devoted to the role of physicians in the management of patients exposed to radiation leakage from a damaged nuclear power plant. "Radiation Disaster Medicine" aims to fill this void based on the response to the Fukushima nuclear accident. Each chapter addresses principles and practices of radiation medicine within the specific context of that accident. Topics covered include the role of physicians in radiation disasters, the concepts of external and internal exposure, prehospital and hospital response, disaster behavioral health, and radiation emergency response from the perspective of national and international institutions. Most of the contributors are active educators and researchers in radiation medicine with first-hand experience in dealing with prehospital triage and management of patients within secondary and tertiary care hospitals in Japan.

More often than not, progress in medicine occurs incrementally. The report of an 'important' new observation is typically greeted by a mixture of excitement and skepticism. Yet the true value of the discovery may not be known for several years until it is confirmed (or refuted) by independently conducted studies. In some cases, controversy may continue to shroud a topic due to the discordant results generated by different research groups. Since the last Gynecologic Oncology volume in the Cancer Treatment and Research series, a number of new areas have emerged that shed new light on the pathogenesis, diagnosis, and treatment of gynecologic malignancies. In this volume of the Cancer Treatment and Research series, I have attempted to integrate articles that highlight some of these newest developments with chapters that provide an overview of selected areas of controversy. This volume is not meant to be an abbreviated text of gynecologic oncology but rather a collection of selected works that can provide the reader with a better perspective on the areas of change within the field. The application of molecular biology to cervical cancer has allowed us to understand more completely the roles of human papilloma viruses and cellular oncogenes in the development of cancer of the uterine cervix.