In 1971, J. Folkman published in the New England Journal of Medicine a hypothesis that tumor growth is angiogenesis-dependent. Folkman introduced the concept that tumors probably secrete diffusible molecules that could stimulate the growth of new blood vessels toward the tumor and that the resulting tumor neovascularization could conceivably be prevented or interrupted by angiogenesis inhibitors. Solid and haematological tumors consist of an avascular and a subsequent vascular phase. Assuming that this depends on the release of angiogenic factors, acquisition of angiogenic capability can be seen as an expression of progression from neoplastic transformation to tumor growth and metastasis.

Beginning in the 1980 s, the biopharmaceutical industry began exploiting the field of antiangiogenesis for creating new therapeutic compounds for modulating new blood vessels in tumor growth. In 2004, Avastin (Bevacizumab), a humanized anti-VEGF monoclonal antibody, was the first angiogenesis inhibitor approved by the Food and Drug Administration for the treatment of colorectal cancer. At present, it has been estimated that over 20,000 cancer patients worldwide have received experimental form of antiangiogenic therapy.

This book offers a historical account of the relevant literature. It also emphasizes the crucial and paradigmatic role of angiogenesis as a biological process and the significance of antiangiogenic approach for the treatment of tumors."

The 7th International Symposium on Platinum and other metal coordination compounds in Cancer Chemotherapy, ISPCC '95, organized by the European Cancer Centre, was held in Amsterdam, the Netherlands, March 1-4, 1995. As with previous ISPCC meetings, the goal of ISPCC '95 was to bring together c1inicians, clinical investigators, scientists, and laboratory workers from many disciplines to promote further collaboration and cooperation in the development of new platinum and other metal coordination compounds as weil as in new ways to use 'c1assical' drugs as cisplatin and carboplatin in the treatment of cancer. Important aspects addressed by experts in the field inc1uded the synthesis and activity of new platinum compounds, the biochemistry and molecular pharrnacology as weil as the c1inical pharrnacology of this c1ass of antineoplastic agents, an overview of current c1inical studies, one special minisymposium on the mechanisms of cell kill of platinum, and one on resistance against platinum compounds. Finally, the current status of development of nonplatinum metal complexes was discussed. This volume contains the contributions of the various speakers at ISPCC '95 and provides an up-to-date and comprehensive overview of this important c1ass of anticancer agents, ranging from synthesis and molecular pharrnacology on one hand to c1inical pharrnacology and cIinical investigations on the other hand. The Organizing Corrunittee and Editors wish to express their gratitude to the contributors to this volume, to the various organizations and pharrnaceutical companies for their generous sponsoring of ISPCC '95, and to the Plenum Publishing Company for their help in producing this volume.

Antibody-drug conjugates (ADCs) represent a promising therapeutic approach for cancer patients by combining the antigen-targeting specificity of monoclonal antibodies (mAbs) with the cytotoxic potency of chemotherapeutic drugs. In Antibody-Drug Conjugates, expert researchers provide detailed protocols for many of the key ADC techniques necessary for working in the field. These chapters and methodologies are aimed at the key tasks necessary to identify a suitable target, properly design the mAb, the linker and the payload, as well as to conjugate them in a reproducible and scalable fashion. Written in the highly successful Methods in Molecular Biology (TM) format, these detailed chapters include the kind of practical implementation advice that guarantees quality results. Authoritative and timely, Antibody-Drug Conjugates aims to further drive ADC development and thus help toward improving cancer treatments of the future.

The last decade has seen a renaissance of the concept of individualized chemotherapy in oncology, markedly stimulated by the development of new in vitro chemosensitivity assays. The clinical utility of drug response assays has been evaluated in clinical trials and the results suggest that assay-assisted therapy selection may improve survival as well as economic outcomes. This volume comprises the proceedings of the first Symposium of the International Society for Chemosensitivity Testing in Oncology, ISCO-1, held in Homburg/Saar, Germany, in September 2001. The topics include: new in vitro drug-testing methods, tumor chemosensitivity assays, and the clinical relevance of assay-directed therapy.

Philip Rosenthal, MD, and a panel of leading malaria experts drawn from academia, the military, and international health organizations survey the latest scientific understanding of antimalarial chemotherapy, emphasizing the molecular mechanisms of resistance and the description of important new targets. Their survey covers the current status of malarial and antimalarial chemotherapy, the relevant biology and biochemistry of malaria parasites, the antimalarial drugs currently available, new chemical approaches to chemotherapy, and possible new targets for chemotherapy. Comprehensive and cutting-edge, Antimalarial Chemotherapy: Mechanisms of Action, Resistance, and New Directions in Drug Discovery clearly delineates all the basic and clinical research now addressing one of the world's major unresolved disease problems, work that is now powerfully driving the rapid pace of antimalarial drug discovery today.

Resistance to chemotherapy, and especially multi-drug resistance, represents a significant barrier to the successful treatment of cancer. This multi-author volume brings together a wide range of up-to-date reviews on different aspects of our knowledge of drug-resistance mechanisms, written by experts in the different areas. Particular attention is paid to recently discovered mechanisms relating to oncogene expression and in particular to proteins involved in regulation and execution of apoptosis. Other important topics covered include DNA repair, topoisomerases, cell cycle control, oxygenation and vascularisation of tumours, LRP, intermediate filament proteins and low-level resistance. Recent developments in understanding the role of efflux pumps (P-170, MRP) in multi-drug resistance are also reviewed. This book will be useful to clinicians and scientists working in the areas of chemotherapy, drug resistance, DNA repair and apoptosis research.

Cutting-edge investigators review the current status of the entire field, from the biology of MMPs through the current clinical studies. The authors include many leading scientists from pharmaceutical companies who present all the latest concepts and results on the preferred design strategies for MMP inhibitors, their molecular mechanisms, and their substrates. In addition, they fully describe their personal research on specific MMP inhibitors, detailing vanguard design strategies, their in vitro activity, the outcome of animal model studies and, where available, their toxicology, safety, efficacy in human clinical trials.
Comprehensive and state-of-the-art, Matrix Metalloproteinase Inhibitors in Cancer Therapy offers basic and clinical investigators alike a richly informative summary of all the latest research on these powerful new drugs, and their high promise as emerging cancer therapeutics.

Infectious Diseases: Smart Study Guide for Medical Students, Residents, Physicians and Clinical Pharmacists consolidates knowledge and information into a step-by-step process that is easy to understand, remember and apply in a clinical setting. The information presented is necessary for medical students and includes comprehensive coverage of the information needed during residency and beyond. The book's content is organized to provide an overview of microbiology and its different microbes. Diseases are discussed in-depth, including cause and microbe, thus guiding the audience from microbe recognition, disease diagnosis and treatments. This is the only book that can be used throughout the lifecycle of treatment. It is appropriate for medical students, residents, practicing physicians, and clinical pharmacists who need to understand the diagnosis, treatment and cure of infectious diseases.

This interdisciplinary volume collates research work on kinesins and cancer. Authors attempt to validate members of the kinesin superfamily as potential targets for drug development in cancer chemotherapy. The work begins by highlighting the importance of kinesins, summarising current knowledge and how they are shown to be crucial for mitosis. Chapters go on to explore how this family of proteins are emerging as a novel target for chemotherapeutic intervention and drug development. Readers will learn how kinesins travel along microtubules to fulfill their many roles in intracellular transport or cell division. Several compounds that inhibit two mitotic kinesins (called Eg5 and CENP-E) have entered Phase I and II clinical trials and are explored in these chapters. Additional mitotic kinesins are currently being validated as drug targets, raising the possibility that the repertoire of kinesin-based drug targets may expand in the future. The book is suitable as a reference standard for the field of kinesins and cancer. It will interest those in academia and pharmaceutical companies, and anyone with an interest in the medical relevance of these proteins, which cutting edge methodologies are now enabling us to understand in astonishing detail.

Great advances were made in the pharmacologic-based treatment of cancer in prior decades. However, despite a marked increase in our understanding ofcell and molecular mechanisms underlying the neoplastic process, therapy for advanced disease remains limited. While the reasons for this are many, it is generally accepted that advanced neoplasms contain a relatively large number of genetic and molecularalterations contributingto the maintenanceofthe neoplastic process. Such a situation precludes easy pharmacologic intervention. However, our ability to detect cancer at an earlier stage, coupled with our increased understandingofcarcinogenesis, are propellingboth basic and clinical scientiststo pursue early intervention/chemopreventive approaches. This is based upon the notion that fewer molecularaberrations are presentearlyon inthedisease process. It also takes advantage ofthe fact that advances in both technology, and in the field ofcancer biology, coupled with a heightened vigilance, have increased our ability to detect early disease more readily. The chemopreventive approach is highly attractive for a number ofreasons. First, treatment ofpre-neoplastic, or early neoplastic, lesions would prevent the significant mobility and mortality associated with advanced neoplastic disorders.

The title of this monograph, Brain Tumor Research and Therapy, is the name of the Conference itself, which had its inaugural meeting in the United States in 1975 andhas since progressed to the international scale. In Japan, the first conference ofits kind was organized by Dr. Takao Hoshino and me and was held at Nikko in 1980, hence its name, the Nikko Conference on Brain Tumor Research and Therapy. Though it started as a small, closed meeting, the conference has grown considerably, and in 1992 it was reorganized as the Japanese Conference on Brain Tumor Research and Therapy and was opened to all neurosurgeons and neuropathologists interested in the study of brain tumor problems and who are participating in this field. The main purpose of the Conference on Brain Tumor Research and Therapy is the candid and informed discussion of the most up-to-date developments in basic re search and clinical treatment of brain tumors. The 3rd Japanese Conference on Brain Tumor Research and Therapy was held at Nasu (Tochigi Prefecture), Japan, in No vember 1994. It was a great honor to welcome many distinguished guests from over seas who kindly attended each session and made valuable contributions.

This book presents a comprehensive collection of essential and up-to-date methods for studying both the biology of microtubules and the mechanisms of action of microtubule-interacting drugs. The book contains a straightforward presentation of readily reproducible protocols, tips for troubleshooting, and advice on avoiding common mistakes. Basic scientists and clinical researchers will benefit from this collection.

Cancer drug discovery has been and continues to be a process of ingenuity, serendip ity, and dogged determination. In an effort to develop and discover better therapies against cancer, investigators all over the world have increased our knowledge of cell biology, biochemistry, and molecular biology. The goal has been to define therapeuti cally exploitable differences between normal and malignant cells. The result has been an increased understanding of cellular and whole-organism biology and an increased respect for the flexibility and resiliency ofbiologically systems. Thus, as some new therapeutic targets have been defined and new therapeutic strategies have been attempted, so have some new biological hurdles resulting from tumor evasion of the intended therapeutic attack been discovered. Historically, anticancer drugs have originated from all available chemical sources. Synthetic molecules from the chemical industry, especially dyestuffs and warfare agents, and natural products from plants, microbes, and fungi have all been potential sources of pharmaceuticals, including anticancer agents. There is no shortage of molecules; the challenge has been and continues to be methods of identifying molecules that have the potential to be therapeutically important in human malignant disease. "Screening" remains the most important and most controversial method in cancer drug discovery. In vitro screens have generally focused on cytotoxicity and have identified several highly cytotoxic molecules. Other endpoints available in vitro are inhibition of proliferation, 3 inhibition of [ H]thymidine incorporation into DNA and various viability assays, based most frequently on dye exclusion or metabolism.

A state-of-the art collection of readily reproducible laboratory methods for assessing chemosensitivity in vitro and in vivo, and for assessing the parameters that modulate chemosensitivity in individual tumors. Chemosensitivity, Volume 1: In Vitro Assays provides a panel of 16 in vitro measures of chemosensitivity in adherent and non-adherent cells for single agents and combinations of agents. In addition to immunohistochemical and imaging approaches, these assays include clonogenic, colorimetric, fluorometric, and physiological assays. Highlights include image analysis to assess drug sensitivity, high throughput approaches using green fluorescent protein, DIMSCAN (a microcomputer fluorescence-based assay), and the ChemoFx assay used in biotechnology. A companion volume, Volume 2: In Vivo Models, Imaging, and Molecular Regulators, provides protocols for classifying tumors into response categories and customizing chemotherapy regimens to individual patients.

This volume commemorates the 30th anniversary of the discovery in 1971 of the first DNA topoisomerases, i.e topoisomerase I in E. coli, then provisionally named omega' protein, by the pioneering work of Jim Wang at Harvard University, who has contributed an article to this volume: Reflections on an accidental discovery' of the enzyme. Many kinds of topoisomerase have since been found from type I through to type VI in a variety of organisms ranging from viruses to higher eukaryote mammals. The wide distribution of enzymes in various forms of life implies that the DNA topoisomerase is essential for life.

In the mid 80's type I and II enzymes were found to be the intracellular targets of a number of efficacious anticancer drugs such as doxorubicin, mitoxantrone, etoposide and camptothecin as a result of a continued efforts of many investigators, especially Leroy Liu and his collaborators at Johns Hopkins University. Readers will find a series of chapters written by researchers actively engaged in the expanding field of topoisomerase and their inhibitors. The series of chapters cover review articles on pharmacology and the molecular mechanism of topoisomerase I- and II-targeting anticancer drugs in mammals and in the yeast Saccharomyces cerevisiae, which has proved to be a superb model organism for studies of anticancer drugs. This volume compiles up-to-date information on the topoisomerase-targeting compounds in clinical and preclinical development as a useful and important reference book for students and researchers in the field of pharmacology, toxicology, oncology and molecular biology.

This collection of thoughtful and provocative articles focused on the key issues in apoptosis, ranges from the role of apoptosis in defining the response of authentic tumor populations to chemotherapeutic agents to the mechanisms coupling DNA damage to the activation pathway of apoptosis. It reviews the profusion of new signaling, modulating, and effector molecules now implicated in apoptosis and whether other routes to "programmed" cell death may exist. Also addressed are the nature of the molecules that will either constitute targets for future drugs or influence the efficacy of current therapies, as well as mechanistic questions on the control of apoptosis. By focusing on essential questions and critically summarizing the overwhelming tide of recent research results, Apoptosis and Cancer Chemotherapy illuminates not only the potential targets for tumor therapy, but beyond that, potential control points for cancer and such diverse diseases as viral infection, neurodegenerative disorders, and stroke. This collection of cutting-edge reviews by established leaders in the field critically summarizes the recent discoveries concerning apoptosis, cell suicide. The book looks forward to the time when such cell death can be controlled to treat cancer and a host of other diseases as diverse as viral infection, neurodegenerative disorders, and stroke.

In Targets for Cancer Chemotherapy: Transcription Factors and Other Nuclear Proteins, a panel of leading basic researchers, pharmaceutical scientists, and clinical oncologists explain in detail the therapeutically-relevant protein targets that contribute to cancer pathology and spell out their implications for cancer drug discovery and clinical application. The authors identify and illuminate selected transcription factor oncoproteins and tumor suppressors, together with nuclear proteins that are central to the phenotype of the tumor cell involved in chromatin control. The emphasis is on new targets and approaches to cancer treatment derived from the cancer cell cycle, gene control targets, and angiogenesis.

The growth in chemotherapy has led to a great need for all those involved to be familiar with safe procedures based on best evidence-based practice. Practical Chemotherapy: a multidisciplinary guide is a comprehensive and straightforward guide describing over 70 widely used chemotherapy regimens, helping to make their prescription and administration safer and less problematic. Checklists throughout the book are specifically tailored for the needs of each professional group involved in treatment, and are intended to help prevent potentially serious mistakes that can occur. This book is unique in its practical emphasis and will be invaluable for doctors, pharmacists and nurses working in oncology and haematology.

Over the last decade, cytokine research has emerged as one of the most exciting and critical fields for providing fundamental knowledge of normal and abnormal human development. Today, it is apparent that cytokines orchestrate growth from the early embryonic stage to maturity and are responsible for the normal function of virtually every organ system. Furthermore, virtually all disease states have been associated, at least in part, with cytokine aberrations. In this volume, the editors have brought together internationally known experts in the field of interleukin research to provide a comprehensive review of the biology of the interleukins and their role in both health and illness, while maintaining a balance between the basic science and clinical aspects. Cytokines: Interleukins and their Receptors should be of interest to a wide variety of researchers including clinical hematologists, oncologists, immunologists, in addition to medical and PhD students and researchers with an interest in cytokines.

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.

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.

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.

Maurie Markman and a panel of distinguished clinicians and leading clinical investigators comprehensively review the current status of regional antineoplastic drug delivery in the management of malignant disease. These authorities present a critical analysis of both the rationale and limitations of regional therapy and discuss potential clinical trials designed to explain the effectiveness of this method of therapy in special settings. Their presentations describe many exciting and innovative strategies for using regional drug delivery in anticancer therapy, including coverage of such areas of special interest as colorectal, skin, lung, pancreatic, ovarian, and gastrointestinal cancers. Comprehensive and authoritative, Regional Chemotherapy: Clinical Research and Practice offers surgical and medical oncologists and clinical cancer investigators a gold-standard review of the current role and future development of this increasingly powerful weapon in the battle against cancer.

Nausea and vomiting are two of the most common side-effects of anti-cancer treatment, and the discovery and clinical application of 5-hydroxytryptamine3 receptor antagonists has transformed the management of these side effects, resulting in a much improved quality of life for cancer patients. This text presents a detailed overview of the management of cancer-treatment induced emesis in a number of different treatment settings, and focuses on the mechanisms and use of 5-HT3 receptor antagonists. Contributions are also included from the points of view of the nurse and the patient.

Cytokines in the Genesis and Treatment of Cancer provides a comprehensive picture of the dual role of host responses in promoting and inhibiting tumor progression. This volume represents an important investigation into the emerging intersection of cancer biology and cancer immunology. The book brings together an impressive array of internationally distinguished investigators who are devoted to the study of cytokines and cancer.