Cancer stem cells werehave originally been identified in leukemia and later in several solid tumor types. They have very different properties from the bulk of the tumor, as they divide much more slowly and have very efficient drug- resistance mechanisms. Current treatments might largely spare cancer stem cells, thus leading to tumor recurrence and metastasis. The recent identification of growth and differentiation pathways responsible for cancer stem cell proliferation and survival will help in the discovery identification of novel therapeutic targets. Developing selective drugs against cancer stem cells offers great therapeutic opportunities but also provides for major challenges regarding preclinical models, therapeutic windows, and clinical study end points.

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."

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.

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.

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.

This book critically evaluates the causal link between cell division machinery and disease. Further, it identifies key open questions in the field and the means for exploring them. Throughout the various chapters, internationally known contributors present the evidence for and against a causal link between key elements of the cell division machinery and diseases such as cancer, neuropathologies, aging, and infertility. A more clinically oriented chapter further discusses the current and future applications of anti-mitotic drugs in these diseases. Cell Division Machinery and Disease is essential reading for graduate or advanced graduate students, researchers or scientists working on cell division as well as clinicians interested in the molecular mechanisms of the discussed diseases.

This multidisciplinary reference explores the concepts and realities of quality of life among cancer survivors in its physical, psychological, cognitive, social, and familial dimensions. Informed by a broad range of fields including genetics, psychiatry, nursing, dentistry, rehabilitation, and ethics, it addresses daily challenges of living for this population, from self-care to cultural concerns and from social interactions to experiences with providers. Family issues of pediatric, young adult, and elder survivors, caregiving parents, and siblings are a major area of concern. And contributors describe interventions for survivors as individuals, in family content, and as part of integrated care across primary and specialty settings. Included among the topics: Play, leisure activities, and cognitive health among older cancer survivors. Genetic mutations in cancer susceptibility genes: a family history of cancer. Cancer patients in a pediatric intensive care unit: a single center experience. The impact of childhood cancer on the quality of life among healthy siblings. When cancer returns: family caregivers and the hospice team. Experiencing cancer services: a story of survival and dissatisfaction. A significant addition to the cancer survivorship literature, Quality of Life Among Cancer Survivors is a practice-building resource for oncology and allied health professionals, health psychologists, and social workers, as well as researchers in these fields.

Molecular biology has rapidly advanced since the discovery of the basic flow of information in life, from DNA to RNA to proteins. While there are several important and interesting exceptions to this general flow of information, the importance of these biological macromolecules in dictating the phenotypic nature of living creatures in health and disease is paramount. In the last one and a half decades, and particularly after the completion of the Human Genome Project, there has been an explosion of technologies that allow the broad characterization of these macromolecules in physiology, and the perturbations to these macromolecules that occur in diseases such as cancer. In this volume, we will explore the modern approaches used to characterize these macromolecules in an unbiased, systematic way. Such technologies are rapidly advancing our knowledge of the coordinated and complicated changes that occur during carcinogenesis, and are providing vital information that, when correctly interpreted by biostatistical/bioinformatics analyses, can be exploited for the prevention, diagnosis, and treatment of human cancers. The purpose of this volume is to provide an overview of modern molecular biological approaches to unbiased discovery in cancer research. Advances in molecular biology allowing unbiased analysis of changes in cancer initiation and progression will be overviewed. These include the strategies employed in modern genomics, gene expression analysis, and proteomics.

We are currently experiencing a fundamental shift in the way in which we approach the characterization of cancer. Never before has the make up of cancer tissues and individual cells been so exhaustively researched and char- terized. We are now capable of producing molecular "fingerprints" that ch- acterize the expression of all known and unknown genes within tumors and their surrounding tissues. More than 30,000 different genes may be measured in each patient's tumor in a single experiment. Simultaneously, novel therapies that exploit the molecular roadmap have been developed and are now being offered to patients. These novel agents, such as Glivec, Herceptin, Iressa, and others, specifically target individual genes within tumors and can produce d- matic responses in some patients. These drugs are only the forerunners of a coming tidal wave of novel therapeutics that individually target specific m- ecules within cancer cells-more than 300 such agents are currently in phase I or II clinical trials. This is an exciting time for cancer specialists and patients alike. However, if we have learned anything from the past 50 or more years of research into cancer, it is that Lord Beaverbrook, in founding the British national health service in the 1950s, was frighteningly prescient when he defined the primary goal of health care to be "Diagnosis, Diagnosis, Diag- sis. " Now, more than ever, it is essential that appropriate diagnostic methods and approaches are applied to the selection of patients for treatment.

This book presents the state of the art of biostatistical methods and their applications in clinical oncology. Many methodologies established today in biostatistics have been brought about through its applications to the design and analysis of oncology clinical studies. This field of oncology, now in the midst of evolution owing to rapid advances in biotechnologies and cancer genomics, is becoming one of the most promising disease fields in the shift toward personalized medicine. Modern developments of diagnosis and therapeutics of cancer have also been continuously fueled by recent progress in establishing the infrastructure for conducting more complex, large-scale clinical trials and observational studies. The field of cancer clinical studies therefore will continue to provide many new statistical challenges that warrant further progress in the methodology and practice of biostatistics. This book provides a systematic coverage of various stages of cancer clinical studies. Topics from modern cancer clinical trials include phase I clinical trials for combination therapies, exploratory phase II trials with multiple endpoints/treatments, and confirmative biomarker-based phase III trials with interim monitoring and adaptation. It also covers important areas of cancer screening, prognostic analysis, and the analysis of large-scale molecular data in the era of big data.

The contents of Colorectal Cancer: Methods and Protocols aim to instruct investigators in all the key genetic, cellular, and molecular biological methods of analyzing colorectal tumors. The focused techniques and assays are described in sufficient detail to allow researchers to start an experiment on colon tumors and proceed from beginning to end as if the expert in the field who has performed these studies were guiding them at the bench. Of note, most of the chapters in this volume are written by those scientists who p- neered these methods and assays in their respective fields. The chapters in Colorectal Cancer: Methods and Protocols describe "state of the art" methods to analyze colorectal tumors, ranging from gross mic- dissection of specimens to specific molecular analyses. Included are coverages of mutational assays, instability testing, immunohistochemical assays, chro- somal studies, and gene expression analyses. The goal of our volume is to facilitate the performance of colorectal tumor biological experiments by investigators at various levels of training-from graduate students and postdoctoral fellows to principal investigators who desire to advance our understanding of colon cancer development.

This volume began with an invitation from the publishers to edit a volume of EXS on Cancer. This invitation undoubtedly derived from my articles in Cellular and Molecular Life Sciences in 2002 and 2003 on the relationships between the morphology, aetiology and pathogenesis of tumours, especially in relation to genetic instability. After many years of teaching the theories of c- cer in undergraduate medical school courses, it seemed to me that the variably chaotic histopathologic features of tumours parallel in some way, the variably unstable genomes of tumour cells, which were being discovered in the 1990s. Thus the title of the volume has come to include morphology, carcinogenesis and genetic instability. The invitation came while I was working with Herrn Dr. med. Hubertus Jersmann (MD Dusseldorf, PhD, now Senior Lecturer in Medicine of the University of Adelaide) and Professor Brian Coghlan (Emeritus Professor of German, the University of Adelaide), on the work of the nineteenth century cancer pathologists, especially David Paul von Hansemann (1858-1920). With the delivery of the manuscripts from the authors of the chapters, it became obvious that a background chapter for the volume could include some of the material which we had "uncovered" together. Because of this, chapter 1 is authored by the three of us, and the "new" material figures prominently.

The contents of this book will be organized into three sections. The first section defines the scope, impact and behaviour of cancer regimen-related toxicities and frames the issue of balancing treatment success and physiological cost. In the second segment of the book, the most current thinking around the pathobiology of specific, common, and representative toxicities is presented by leading researchers and translational scientists. The final portion of the book discusses the common biological relationships between toxicities, bioinformatical approaches to analysing key and common pathways, and strategies for the development of effective interventions.

Lymphangiogenesis and Cancer Metastasis introduces the new field of lymphatic vessel growth and development, and its relationship to the metastatic spread of cancer cells.

The book covers all aspects of this new field from the fundamental role that protein growth factors and their receptors play in lymphangiogenesis to the potential application of these advances to cancer diagnosis and treatment. Other clinical aspects explored include the mechanisms and importance of lymph node metastasis, the role of the lymphatics in lymphangioleiomyomatosis and Kaposi s sarcoma, and approaches for imaging lymphatics in cancer.

The book also covers the innovative approaches taken by researchers to explore new roles for lymphatic vessel biology in the context of cancer. The information presented in this volume, which describes the revolutionary concepts of tumor lymphangiogenesis, will be of interest to all students, scientists and oncologists who are seeking to understand the complexities of tumor metastasis.

Key Features:

• Presents fundamental concepts of tumor lymphangiogenesis and the molecules which control this process
• Provides a comprehensive summary of current research in this ground breaking area
• Provides a book which links progress in basic tumor and developmental biology with current and future oncology practise
• Is an essential text for molecular biologists, cell biologists and oncologists seeking to understand the implications of this rapidly developing area.

In the past five years, a surprising and intense resurgence in interest in vitamins and other micronutrients and their role in health and dis ease has occurred. The recognition has emerged that vitamins not only are essential for life .in that severe nutritional deficiencies occur in their absence, but that these compounds may also serve as natural inhibitors of cancer. Synthetic alterations of the basic vitamin A mole cule have also resulted in the production of compounds that are more potent as anticancer agents than the natural substance and may have substantial therapeutic activity as well. Whether other vita mins can be changed or altered to produce a better anticancer effect than the native compound has been little explored to date, but should be a fruitful pursuit for future study. In our concluding remarks to the First International Conference in 1982, we speculated that rapid advances in our understanding of vi tamins would occur in the next few years and that large-scale inter vention trials of vitamins as preventive agents in defined human pop ulations would be started. This anticipated generation of data on vitamins and their interactions has proceeded rapidly and the impor tance of interactions between vitamins and other micronutrients in the prevention setting has become better appreciated. Currently, more than 25 intervention trials with a variety of target populations using vitamins and other micronutrients have been started, but it re mains too early for meaningful analysis of the results to date."

Liver Cancer, the inaugural volume in the M.D. Anderson Solid Tumor Oncology series, provides the general surgeon, surgical oncologist, and medical oncologist with the most up-to-date and current standard of multimodality care for hepatobiliary cancer. Surgical approaches, chemotherapy, immunotherapy, gene therapy, and radiotherapy are all presented, giving the practitioner a much needed, comprehensive perspective on all aspects of patient care. The MD Anderson Solid Tumor Oncology series features cutting-edge, indepth information of vital interest to all practitioners in today's captitated financial milieu. Providers must understand how their component of care interdigitates with the varied medical and surgical teams and apply multimodality approaches to their practice environments.

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.

This second edition has been updated in a user-friendly layout that makes its comprehensive information extremely accessible. The handbook, written for all physicians who treat cancer patients, provides a survey of current therapeutic concepts of solid tumors and hematologic malignancies in internal oncology. Each individual chapter of this shortened new edition is structured in the same way and features a brief outline or tabular summary of the main aspects of epidemiology, pathology, staging, and diagnosis. The main focus is on the therapeutic strategy, i.e., an interdisciplinary approach to systemic drug therapy. Surgical and radiological concepts of treatment are also covered, as are supportive care, pain relief methods and ethical problems. This title is a must for clinicians and practitioners as well as interns, residents and postgraduate students.

Advances in genetics are transforming estimates of an individual 's risk of developing cancer and approaches to prevention and management of cancer in those who may have increased susceptibility. Identifying and caring for patients with hereditary cancer syndromes and their family members present a complex clinical, scientific and social challenge. This textbook, by leading experts at Massachusetts General Hospital Cancer Center, highlights the current understanding of the genetics of hereditary cancers of the breast, ovary, colorectum, stomach, pancreas, kidney, skin, and endocrine organs. Practical guidelines for the use of genetic testing, cancer screening and surveillance, prophylactic surgery, and promising targeted therapeutic agents are discussed.

In addition, ongoing research involving genome-wide screens to identify novel modest risk-associated genetic loci are explored, along with new approaches to the application of genetic markers in guiding therapeutic options.

The European Organization for Cooperation in Cancer Prevention Studies (ECP) was established in 1981 to promote collaboration between scientists working in the various European countries on cancer causation and prevention. In order to achieve this aim, various working group- to deal with specific cancers or aspects of cancer aetiology, and to explore the opportunities for advances on a cooperative European basis - were established. It was also decided to hold annual symposia to draw general attention to fields in which there seemed to be many opportunities for progress in matters of prevention. These symposia have been devoted to themes of high priority to cancer prevention: "Tobacco and Cancer" (1983), "Hormones and Sexual Factors in Human Cancer Aetiology" (1984), "Diet and Human Carcinogenesis" (1985), "Concepts and Theories in Carcinogenesis" (1986)," Preventive Strategies for Cancer related to Immune Deficiencies" (1987), "Gastric Carcinogenesis" (1988), and "Breast, Ovarian and Endometrial Cancer: Aetiological and Epidemiological Relationships" (1989). This volume contains the proceedings of the 1990 ECP symposium held in Heidelberg, FRG, at the Deutsches Krebsforschungszentrum (DKFZ), on April 2-3 on "Causation and Prevention of Human Cancer." We are indebted to the speakers for their contribution during the symposium and for their prompt submission of manuscripts. We are grateful to the sponsors, SmithKline Diagnostics and Rohm Pharma. Our special thanks go to Dr M.C. stanei-Gueur for preparing and typing the camera forms of all manuscripts.

A cutting-edge review of the important issues underlying the therapeutic use of nucleic acid-mediated gene silencing. Topics range from basic methodology and delivery to targeting and clinical targets. The authors thoroughly explain the latest developments in RNA biology, as well as the underpinnings of RNA interference, oligodeoxynucleotide delivery into cells, and strategies for targeting these molecules to accessible regions within the mRNA. They also provide some examples of how these new therapeutic compounds are being used clinically.

This book focuses on the development of stapled peptides, a novel molecular modality used to regulate aberrant intracellular protein-protein interactions (PPIs). The author designs and presents a novel helical peptide stabilization methodology by constructing a chiral cross-linker moiety, namely "chiral center induced peptide helicity (CIH)". The book demonstrates that a precisely positioned carbon chiral center on tether can decisively determine the secondary structure of a peptide, and that the R-configured peptide is helical, while the S-configured peptide is non-helical. Further, it reports that helicity-enhanced R isomer peptides displayed significantly enhanced cell permeability and target binding affinity, as well as tumor inhibition efficiency, in comparison to S isomer peptides. The book will not only advance readers' understanding of the basic principle of stapled peptides, but also accelerate the clinical transformation of stapled peptide drugs.