Progress in Cell Cycle Research is a new annual series designed to be the source for up-to-date research on this rapidly expanding field. Review articles by international experts examine various aspects of cell division regulation from fundamental perspectives to potential medical applications. Researchers as well as advanced undergraduate and graduate students in cell biology, biochemistry, and molecular biology will benefit from this series.

The present book is a collection of original contributions by specialists in fields related to the more advanced methods presently used or foreseen in the near future for cancer therapy. The use of larger nuclear installations, like particle accelerators and nuclear reactors in oncology is treated in detail, giving an interesting overview of their present and future potential. The aim of the book is to clarify the present state of the art and to encourage new interest in the many fields related to cancer research. The book is particularly suitable for people working in cancer research, but also in other fields, like particle accelerators, nuclear reactors, nuclear medicine and radio-pharmaceutical research. The methods presented in the book are sometimes tentative or not completely established, but clearly reveal the efforts being made to acquire new knowledge for the solution of one of the more serious problems involving the whole of mankind. The book is also required reading for those who want to be informed about the medical research work in large nuclear installations and the most advanced trends in nuclear medicine.

In Leukemia and Lymphoma: Detection of Minimal Residual Disease, hands-on experts describe and discuss the minimal residual disease (MRD) methods they have successfully pioneered for leukemias and lymphomas. They apply reverse transcription PCR (RT-PCR) to acute myeloid leukemia (AML), chronic myelogenous leukemia (CML), and acute promyelocytic leukemia (APL). Other PCR methods are used for Non-Hodgkin's Lymphoma and for the monitoring of follicular lymphoma. Additional chapters address the use of real-time quantitative PCR (RQ-PCR), the emergent method of choice, in patients with acute lymphoblastic leukemia (ALL), the evaluation of MRD techniques in clinical trials, and the application of flow cytometry techniques.

Written for residents and practitioners of otolaryngology, medical oncology, radiation oncology, and maxiollofacial surgery, this book provides the reader with a comprehensive, concise discussion of the best evidence available on which to base clinical decisions needed when managing patients with squamous cell carcinomas of the oral cavity, pharynx and larynx. Because of its accessible and practical format, this book is considerably different than other related titles on the market. Formatted with questions at the beginning of each chapter that are then answered with evidence and best practices available for each case, each chapter addresses situations the clinician is likely to face in the diagnostic evaluation and treatment of a patient with cancer of the head and neck. Most clinical decisions in the management of cancers of the head and neck region are based on the results of a few controlled, randomized clinical trial trials (Evidence Level I). However, most decision-making is based on the results of case-control studies (Evidence Level II), descriptive studies, reports of expert committees, or opinions of respected authorities (Evidence Level III). This information is scattered throughout the literature and often comingled with information about other topics. Therefore, there is a need for a publication in which the evidence pertinent to making decisions regarding a particular clinical problem is distilled from the literature and presented in a single concise, clinical, situation-driven source. Cancer of the Oral Cavity, Pharynx and Larynx: Evidence-Based Decision Making is just such a resource.

In June 1998 the Fourth International Workshop on Digital Mammography was held in Nijmegen, The Netherlands, where it was hosted by the department of Radiology of the University Hospital Nijmegen. This series of meetings was initiated at the 1993 SPIE Biomedical Image Processing Conference in San Jose, USA, where a number of sessions were entirely devoted to mammographic image analysis. At very successful subsequent workshops held in York, UK (1994) and Chicago, USA (1996), the scope of the conference was broadened, establishing a platform for presentation and discussion of new developments in digital mammog raphy. Topics that are addressed at these meetings are computer-aided diagnosis, image processing, detector development, system design, observer performance and clinical evaluation. The goal is to bring researchers from universities, breast cancer experts, and engineers together, to exchange information and present new scientific developments in this rapidly evolving field. This book contains all the scientific papers and posters presented at the work shop in Nijmegen. Contributions came from as many as 20 different countries and 190 participants attended the meeting. At a technical exhibit companies demon strated new products and work in progress. Abstracts of all papers were reviewed by members of the scientific committee. Many of the accepted papers had excellent quality, but due to limited space not all of them could be included as full papers in these proceedings. Papers that were rated high by the reviewers are included as long or short papers, others appear as extended abstracts in the last chapter."

Leading researchers and clinicians join forces to explain how malignant melanoma develops from its benign precursor cell type. The authors focus on the molecular mechanisms involved in melanogenesis, in the malignant transformation of melanocytes, and in the further progression of primary melanomas into invasive and metastatic melanomas. They also review recent advances in our understanding of the basic biology of melanocytes and the development, migration, and differentiation of melanoblasts into melanocytes. The book provides an up-to-date understanding of the progressive mechanisms of oncological development in malignant melanoma, a likely model of malignant progress for other types of cancer, and the ongoing development of novel therapeutics.

Target Discovery and Validation: Reviews and Protocols, Volumes 1 and 2 review the most progressive and current methods for drug target discovery and validation. These volumes explore how recent improvement in understanding the molecular mechanisms of human pathology is impacting drug target discovery in the laboratory and in real therapeutics, specifically for cancers and autoimmune disorders.
Volume 1 focuses on novel and innovative techniques, and presents the most up-to-date protocols available for maximizing the likelihood of achieving target-selective inhibition in vivo while minimizing side effects. The profound impact of genomics, proteomics and bioinformatics on target discovery is explored, and specific attention is given to the role of transgenic and knockout animals in functional genomics and target validation. Cancer researchers will find tremendous value in the molecular classification of breast cancers and the review of protocols for tumor antigens and cancer vaccines. The methods and protocols collected here, all reviewed by leading scientists and clinicians, present the practical details necessary for translating the enormous discovery potential of the genome into real therapeutic products.
Volume 2 collects all the practical details required for efficient translation of discovered targets into real pharmaceutical drugs. Specific targets in cancers and autoimmunity are described and the potential of using siRNA's, antisense oligonucleotides and RNA aptimers in patients is reviewed. This volume explores the tremendous impact of the application of genotyping and gene expression profiling on the future of healthcare, and presents cutting-edge protocols to aid inbringing agents against specific targets closer to application in the clinic.
Collectively, these volumes provide a thorough review of the most cutting-edge methods available for each step in drug target identification, validation, and clinical application. For researchers, an understanding of available methods aids in the creation of innovative experiments in the laboratory, and the successful translation of target discovery to real therapeutics.

Knowledge about cancer genetics is rapidly expanding, and has implications for all aspects of cancer research and treatment, including molecular causation, diagnosis, prevention, screening, and treatment.

Additionally, while cancer genetics has traditionally focused on mutational events that have their primary effect within the cancer cell, recently the focus has widened, with evidence of the importance of epigenetic events and of cellular interactions in cancer development. The role of common genetic variation in determining the range of individual susceptibility within the population is increasingly recognized, and is now being widely addressed using information from the Human Genome Project. These new research directions will highlight determinants of cancer that lie outside the cancer cell, suggest new targets for intervention, and inform the design of strategies for prevention in groups at increased risk.

Today, the NCI is putting more and more money into research into the genetics of cancer. The very first of the NCI s stated research priorities is a project called The Cancer Genome Atlas. The Cancer Genome Atlas (TCGA) is a comprehensive and coordinated effort to accelerate the understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing. The NCI and the NHGRI (National Human Genome Research Institute, where the series editor is employed) have each committed $50 million over three years to the TCGA Pilot Project.

This book proposes cover the latest findings in the genetics of male reproductive cancers; specifically cancers of the prostate and testes. The volume will cover the epidemiology of these cancers; model systems, pathology, molecular genetics, and inherited susceptibility."

This book is a comprehensive review of the current knowledge on cytokines and cancer. Cytokines play a variety of roles in cancer, both as components of pathogenetic mechanisms, as well as agents used in the treatment of certain malignancies. To date, there has not been a book that covers both basic science and translational/clinical research in the field of cytokines in malignancies. This book is written by leading figures in the field of cytokine biology and cytokine therapeutics and is specifically focused on this subject. The book is divided into two parts. The first part is focused on current developments in the basic science field. There is a particular emphasis on novel mechanisms of cytokine actions in malignant cells. The second part deals with translational and clinical research in the field, and many of the authors of these chapters were among the first to introduce several cytokines in the treatment of certain tumors. Collectively, the information provided in this book will be helpful to people in the medical field at several levels, including medical students, interns, residents, clinical and basic science researchers, as well as oncologists in practice.

Biological Basis of Geriatric Oncology highlights research issues that are specific to geriatric oncology in the field of carcinogenesis and cancer prevention and treatment, based on the biologic interactions of cancer and age. It illustrates the benefit of the principles of geriatrics in the management of cancer in the older individual.

This volume provides a frame of reference for practicioners of any specialties involved in the management of older patients and for oncologists involved in the management of cancer of older individuals. It is a source for basic and clinical scientists exploring the interactions and emerging information of cancer and aging.

Quantification of the proliferative characteristics of normal and malignant cells has been of interest to oncolo gists and cancer biologists for almost three decades. This interest stems from (a) the fact that cancer is a disease of uncontrolled proliferation, (b) the finding that many of the commonly used anticancer agents are preferentially toxic to cells that are actively proliferating, and (c) the observa tion that significant differences in proliferation characteristics exist between normal and malignant cells. Initially, cell cycle analysis was pursued enthusiastically in the hope of gener ating information useful for the development of rational cancer therapy strategies; for example, by allowing identi fication of rapidly proliferating tumors against which cell cycle-specific agents could be used with maximum effec tiveness and by allowing rational scheduling of cell cyc- specific therapeutic agents to maximize the therapeutic ratio. Unfortunately, several difficulties have prevented realiza tion of the early promise of cell cycle analysis: Proliferative patterns of the normal and malignant tissues have been found to be substantially more complex than originally an ticipated, and synchronization of human tumors has proved remarkably difficult. Human tumors of the same type have proved highly variable, and the cytokinetic tools available for cell cycle analysis have been labor intensive, as well as somewhat subjective and in many cases inapplicable to humans. However, the potential for substantially improved cancer therapy remains if more accurate cytokinetic infor mation about human malignancies and normal tissues can be obtained in a timely fashion."

The previous volume of this series on soft tissue sarcomas highlighted the importance of the multidisciplinary approach to treatment, the focus of which is continued in the present edition. Proper diagnosis and staging remain the cornerstone of the treatment strategy. Sophisticated histopathology techniques and growing consensus on grading systems have further increased the importance of the histopathologist in providing estimates of the prognosis of the patient as well as providing data for the planning of treatment strategy. The use of cytogenetics is relatively new in this field. This might enable the distinction of subgroups in specific histological tumor types. Furthermore, molecular biological studies not only help to reveal inherited predispositions and details in oncogenesis in tumor development, but they may also provide additional predictive factors for tumor behavior. Further data on treatment strategy will be provided by diagnostic imaging, a field in which the role of magnetic resonance imaging is rapidly developing. As far as actual treatment is concerned, surgery still provides the major chance for cure. In view of the endeavor to be as sparing as possible, the addition of radiotherapy to surgery is of utmost importance. Usually radiotherapy is given after surgery, but the optimal sequence of the two modalities still needs to be defined. The combined use of surgery with radiotherapy and/or chemotherapy does have an impact on wound healing.

A comprehensive review of the recent developments in DNA repair researchthat have potential for translational applications. The book explains in detail the various biologicalmechanisms by which cancer cells can circumvent anticancer therapy and limits its usefulness in patients. They also review the impact of such novel inhibitors of DNA repair mechanisms as methylguanine-DNA-methyltransferase. Also examined are inhibitors of other DNA repair enzymes such as PARP and DNA-PK. The book captures-for both cancer researchers and oncologists dealing with hallmark "relapse" or "drug resistance" phenomena on a daily basis-the many exciting new uses of DNA repair inhibitors, either alone or in combination with anticancer therapies.

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.

This book is a rich source of information on biomarkers applicable to the pathology of neoplastic disorders of the brain. Thorough descriptions are provided of the techniques currently available for clinical and experimental evaluation of biomarkers in brain neoplasms, including in situ hybridization, array-based methods, methylation profiling, next-generation sequencing, and practical gene panels. Incorporation of multiple biomarkers in the development of molecular subgroups with biologic and therapeutic relevance is also discussed. A section on biobanking covers the equally important topic of optimal preservation of tissue and includes consideration of ethical considerations raised by the use of tissue obtained in clinical settings. The closing section discusses the major categories of neoplastic disorders involving the nervous system, with emphasis on diagnostic, prognostic, and predictive biomarkers used in the pathologic evaluation of different types of brain tumor.

It is widely recognized that the host response to tumor munotherapy of experimental metastases in animal systems progression is an important determinant in cancer growth which are beginning to be developed for ultimate clinical and progression. Indeed, as indicated in Volume I of this trials of human cancer metastasis. series, the process of cancer growth and progression, leading This volume explores a variety of host properties that to tumor invasion and metastasis, is dependent upon the influence tumor development including dormancy, regress complex, dynamic interactions between the properties of the ion, and recurrence. In addition, current knowledge of the tumor as well as the properties of the host. While Volume III response of the central nervous system to cancer, cardiac of this series reviews in great detail the influence of tumor and pulmonary complications, dermatologic effects and development on the host, this volume emphasizes the in hematologic complications of malignancies is presented. fluence of the host on tumor development. These host re The endocrine and metabolic function of cancer patients, as sponses include host anti-tumor immune reactivity, tumor well as the production of hormones by tumors is also review dormancy, cachexia, multiple endocrine and paraneoplastic ed.

A cutting-edge collection of readily reproducible molecular techniques to better understand, classify, and treat lymphoma. Among the highlights are methods to use immunoglobulin gene rearrangements as markers of clonality, to exploit patterns of somatic mutation in the variable regions to indicate at which stage transformation occurred, and to apply gene arrays to the question of biological heterogeneity in morphologically similar diseases. Research methodologies that are highly likely to become routine practice in the future, such as DNA microarray and immunoglobulin V-gene rearrangements, and measurement of minimal disease, are included. There are also molecular techniques for providing for producing novel therapeutics, such as a DNA vaccine with patient-specific sequences derived from the lymphoma in question.

Methylation of DNA at cytosine residues as well as post-translational modifications of histones, including phosphorylation, acetylation, methylation and ubiquitylation, contribute to the epigenetic information carried by chromatin. These changes play an important role in the regulation of gene expression by modulating the access of regulatory factors to the DNA. The use of a combination of biochemical, genetic and structural approaches has allowed demonstration of the role of chromatin structure in transcriptional control. The structure of nucleosomes has been elucidated and enzymes involved in DNA or histone modifications have been extensively characterized. Since deregulation of epigenetic marks has been reported in many cancers, a better understanding of the underlying molecular mechanisms bears the promise that new drug targets may soon be found. The newest developments in this quickly developing field are presented in this book.

Heme oxygenase is rapidly taking its place as the centerpiece of multiple inter acting metabolic systems. Only 25 years ago heme oxygenase and its metabolic prod ucts appeared to be merely a simple metabolic system-one substrate, heme; one enzyme, heme oxygenase; and one set of products, iron to be recycled, and bilirubin and carbon monoxide to be disposed. From a group of about 25 people in 1974, as judged by attendance at various Gordon conferences, heme oxygenase has, in the year 2000, attracted working scientists-and clinicians I might add-by the hundreds and has produced referenced publications by the thousands. It is well-deserved attention. Heme oxygenase system is now similar to the metabolic networks surrounding glucose in those complex maps of glycolytic and non-glycolytic metabolic pathways, which we had to memorize as students. The relevance of heme oxygenase to regulatory biology was recognized many years ago, but the work conducted over the past five years has created a new wave of emphasis focusing on genetic manipulation to alter heme oxygenase gene expression, the regulatory actions of heme oxygenase products including carbon monoxide, and the significance of changes in the heme oxygenase system. The physiological and pathological relevance of heme oxygenase in the brain, heart, liver, bone marrow, organ transplant, lung and kidney, opens many areas of investigation in various dis ciplines. Advances in the pharmacology of bilirubin and its ability as an antioxidant have provided a new avenue in clinical research.

At the moment, there is no dedicated book to summarize the roles, the significance, and potential therapeutic targeting of transcriptional factors from the perspective of signaling cascade, and thus, directly impacting the functionality of transcriptional factors in cancer. In addition, this book will offer a comprehensive basic and clinical science behind the functions of representative core transcriptional factors. These chapters will serve as a treasure for all those who have an interest in the basis, progression, and targeting of human cancer. Each chapter will be intended to provide comprehensive, up-to-date information by the leaders about the physiologic and pathologic roles of TFs in specific representative organ systems of prime importance. The book will consist of chapters that will give biomedical students, under and graduate students, basic sciences and clinical cancer fellows, residents and researchers, and oncology educators will get a thorough summary of the overall subject. The readers will be able to understand the important current information and views on specific TFs and its role in cancer in areas outside their own expertise or experience. A special emphasis will be also placed on the "classic" papers as well as perspectives on future directions for the field.

Molecular Pathology of Gynecologic Cancer focuses on putting successful molecular strategies into practice for the treatment of gynecologic cancer. The volume begins with an explication of the editorsa (TM) hypothesis that cancer is mainly a disease of the cell cycle, based on the deregulation of the physiological process of cell reproduction. The following eleven chapters focus on specific issues in gynecologic cancers, including: a proposed model of ovarian serous carcinogenesis, molecular markers for ovarian epithelial cancer, an overview of the pathology of endometrial cancer, molecular genetic aspects of endometrial carcinoma and cervical cancer, a natural history of Human Papilloma Virus (HPV) as it relates to cervical cancer, and hereditary issues in gynecologic cancers. The concluding chapter proposes and outlines a holistic approach to the treatment of female cancer patients. This new volume in Humanaa (TM)s Current Clinical Oncologya"[ series will be necessary reading for clinicians and experimental researchers alike.

One of the major advances of the last decade concerning the treatment of patients with soft tissue sarcomas is that an increased number of patients are being discussed in multidisciplinary teams prior to the initial treatment. The present volume on soft tissue sarcomas in the series Cancer Treatment and Research reflects the multidisciplinary approach with a focus on recent developments. The availability of new histopathologic techniques has reduced the number of unclassified sarcomas and has furhter increased the importance of the histo pathologist in providing estimates of the prognosis of the patient as well as data for the planning of treatment strategy. Further data for this strategy will be provided by diagnostic imaging. In this field, the role of magnetic reson ance imaging has been further defined. Of utmost importance is the recent trend toward consensus in staging. The modification of the staging system of the American Joint Commission for Cancer Staging and End Results Report ing brings the possibility of a single staging system within reach in the next decade. As surgery still provides the only chance for cure, the importance of being the most sparing as possible is obvious. For this reason, radiotherapy has been applied with success. The introduction of relatively new radiation tech niques is therefore being observed with interest."