This book reviews recent breakthroughs in anti-cancer drug discovery. Building on the previous volume in the series, it outlines some of the most significant developments that have occurred in the field in the subsequent period that have led to new drug approvals or promising clinical candidates. The volume is divided into chapters that each relate to a specific protein or protein class. Each chapter provides an overview of the underlying biology and then emphasises the medicinal chemistry strategies and tactics that led to the most significant drugs and drug candidates. A summary of clinical data and the future outlook for the field is also provided. Each chapter is authored by experts in the topic and who have themselves made significant contributions to their respective fields.

This volume reviews the current state of research on immune checkpoints and offers novel concepts. It discusses the two most important immune checkpoints: T lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1). It shows that antagonistic antibodies against these two molecules are highly effective in the treatment of various cancers and that PD-1 and CTLA-4 have been linked to the suppression of T-cell receptor signaling and co-stimulatory molecules. Further, the volume examines other agents, a number of cells, receptors and signaling molecules, that are also involved in the regulation of T-cell activation and extends the concept of immune checkpoints to "molecules and cells that negatively regulate T-cell activation". Playing essential roles in immune homeostasis, they could offer new targets for cancer immunotherapy, and for the therapy of autoimmune diseases. Written by internationally respected scientists, this book will appeal to basic scientists, clinicians, drug development researchers, and advanced students alike.

Cancer is a complex disease. Only 5-10% of human cancers are hereditary in nature. Many of us think of environmental agents when we think of carcinogens. The environment includes all that surrounds us, and environmental influences include not only chemical, physical and biological toxicants, but also diet and lifestyle. In this broadest sense, the environment contributes substantially in the development of human cancer. This book will describe how environment contributes to malignant transformation leading to profound changes in the genetic and signaling networks that control the functioning of the cell. It will critically discuss the understanding of the effects of environment on the development, progression and metastasis of cancer with current knowledge of the signaling networks that support functioning of transformed human cells. Genes and environmental factors that influence the origins of cancer are not necessarily the same as those that contribute to its progression and metastasis. Susceptibility gene variants for each specific cancer are being identified with emerging evidence of gene environment interaction. Gene-environment interactions will be discussed through each specific cancer-based approach to address the question of how genetic variations can influence susceptibility to the individual type of cancer. It will also highlight and summarize epigenetic changes that increase the risk for susceptibility to a particular type of cancer, particularly in the presence of specific environmental factors. Thus, this book will contain chapters from the world s experts focused on the current evidences that support the role of environment in the cancer etiology and in the growth of malignant lesions, and discuss who may be susceptible to environmental influences."

This issue of Hematology/Oncology Clinics, guest edited by Dr. Glenn J. Hanna, will focus on Head and Neck Cancer. This issue is one of six selected each year by our series consulting editors, Dr. George P. Canellos and Dr. Edward J. Benz. This issue addresses the evaluation and management of the complex head and neck cancer patient with articles focused on unique epidemiology and therapeutic principles by subsite of disease. Additional information relevant to rare head and neck malignancies is included. The issue further focuses on the evolving applications of minimally invasive surgery in oropharynx cancer and the role of immunotherapy in the management of advanced disease. Topics include: Radiologic Evaluation of the Head and Neck Cancer Patient, Robotic and Endoscopic Approaches to Head and Neck Surgery, Cancer of the Oral Cavity and Lip, Cancer of the Oropharynx and the Association with Human Papillomavirus, Cancer of the Larynx and Hypopharynx, Cancer of the Nasal Cavity and Paranasal Sinuses, Cancer of the Nasopharynx and the Association with Epstein-Barr Virus, Salivary Glands Cancers, Thyroid and Parathyroid Cancers, Cutaneous Malignancies of the Head and Neck, Managing Recurrent and Metastatic Head and Neck Cancer, and Immunotherapy for Head and Neck Cancer. Provides in-depth, clinical reviews on head and neck cancer, providing actionable insights for clinical practice. Presents the latest information on this timely, focused topic under the leadership of experienced editors in the field; Authors synthesize and distill the latest research and practice guidelines to create these timely topic-based reviews.

In the past, many tumor marker laboratory tests have not been sensitive enough for the very early detection of cancer. However, many of them have nonetheless proved useful in monitoring therapy, following the course of the tumor, and predicting prog- nosis. Today, cancer may be viewed as a genetic disease with various specific chromo- somal and nucleotide aberrations, such as mutations, deletions, gene amplification, gene rearrangements, and translocations occurring during the transformation of a nor- mal cell into a malignant cell. The considerable advances in technology during the past several years have greatly enhanced our ability to detect human cancers in the very early stages of tumor forma- tion. These technologies include: (1) nucleotide molecular assays (genomics); (2) proteomics (multiplex protein measurements); (3) DNA microarrays; and (4) bio- informatics. Many of these technologies are already helping in the integration and use of multiple biomarkers for tumors. Although the individual biomarkers may reveal only limited information, the use of multiple biomarkers can help markedly elevate the diagnostic capabilities for early detection of tumors.

The annual research conference for 1996 of the American Institute for Cancer Re search was again held at the Loews L'Enfant Plaza Hotel in Washington, DC, August 29 and 30. The topic for this, the seventh in the series, was "Dietary Fat and Cancer: Genetic and Molecular Mechanisms. " Two separate presentations were given as the conference overview. "Fat and Cancer: The Epidemiologic Evidence in Perspective" noted that die tary fat can be saturated, largely from animal or dairy sources, or mono- or polyunsatu rated, mostly from plant sources. Unlike animal fats, fish contain relatively high levels of protective omega-3 fatty acids. Although the hypothesis that dietary fat is associated with cancer is plausible, the mechanisms involved are reasonable, and many animal studies support the hypothesis, there are many obstacles in any direct extrapolation to humans, in cluding imprecise measures of dietary fat intake, variability in individual diets, and spe cies variations. Despite these limitations, there is a weak positive correlation between colon cancer and dietary fat intake, but with substantial differences for various ethnic groups. In the case of breast cancer, there is substantial variation among countries and eth nic groups, but the overall evidence indicated an association with fat in the diet. Epidemiologic studies of dietary fat and prostate cancer are more consistent and most show a positive relationship. However, it was not clear which types of dietary fat were im plicated in the effect."

1 Biochemical, Immunological, and Molecular Markers of Hemopoietic Precursor Cells.- 1. Introduction.- 2. Biochemical Markers.- 2.1. Terminal Deoxynucleotide Transferase.- 2.2. Enzymes in Nucleotide Metabolism.- 3. Immunological Markers.- 4. Molecular Markers.- 5. Analysis of Human Hemopoietic Ontogenesis by Immunological and Molecular Markers.- 6. New Opportunities for Immunological and Molecular Markers: Minimal Residual Disease Detection and Therapeutical Approaches.- 7. References.- 2 Cell Surface Markers in Leukemia and Lymphoma.- 1. Introduction.- 2. B Cells.- 2.1. Normal B-Cell Ontogeny.- 2.2. B-Cell Leukemias and Lymphomas.- 3. T Cells.- 3.1. Normal T-Cell Ontogeny.- 3.2. T-Cell Leukemias and Lymphomas.- 4. Myeloid Cells.- 4.1. Normal Myeloid Ontogeny.- 4.2. Myeloid Leukemias.- 5. Summary.- 6. References.- 3 Cytoskeletal Organization of Normal and Leukemic Lymphocytes and Lymphoblasts.- 1. Introduction.- 2. Microfilaments in Normal and Leukemic Lymphocytes and Lymphoblasts.- 2.1. Actin and Actin-Associated Proteins in Nonmuscle Cells.- 2.2. Actin Isoforms.- 2.3. Organization of Actin in Normal Lymphocytes.- 2.4. Interactions between Actin and Surface Antigens in Lymphocytes.- 2.5. Actin in Leukemic Lymphocytes and Lymphoblasts.- 3. Intermediate-Size Filaments in Normal and Leukemic Lymphocytes and Lymphoblasts.- 3.1. The Intermediate Filament System.- 3.2. Distribution of Vimentin in Lymphocytes in Normal Conditions.- 3.3. Vimentin in Neoplastic Lymphocytes and Lymphoblasts.- 3.4. Expression of Cytokeratin in Lymphoid Tissues.- 4. Microtubules in Lymphoid Cells.- 5. Organization of Spectrin in Lymphocytes.- 6. Conclusions.- 7. References.- 4 Signaling Events in T-Lymphocyte-Dependent B-Lymphocyte Activation.- 1. Introduction.- 2. B-Cell Antigen Receptor-Mediated Signaling.- 3. Molecular Bases of T-Cell-Mediated B-Cell Signaling.- 4. Biological Evidence for Ia-Mediated Signal Transduction.- 5. Biochemical Evidence for Ia-Mediated Signal Transduction.- 6. Conclusions.- 7. References.- 5 IgE Receptors on Lymphocytes and IgE-Binding Factors.- 1. Introduction.- 2. Historical Overview.- 3. Fc?RII on Lymphocytes.- 3.1. Fc?RII-Bearing Cells.- 3.2. Function of Fc?RII.- 3.3. Molecular Properties of Fc?RII.- 3.4. Regulation of Fc?RII Expression on Lymphocytes.- 4. IgE-Binding Factors.- 4.1. Rat.- 4.2. Murine.- 4.3. Human.- 5. Glycosylation-Regulating Factors: GEF and GIF.- 5.1. Rat.- 5.2. Murine.- 6. Interleukin 4 and Gamma Interferon.- 7. CD23 Antigen.- 8. Conclusion.- 9. References.- 6 Lymphocyte-Mediated Cytolysis: Role of Granule Mediators.- 1. Role of Granules and Perform in Lymphocyte-Mediated Killing.- 1.1. The Granule Exocytosis or Secretion Model for Cell Killing.- 1.2. Cytoplasmic Granules and Perform as Mediators of Cytotoxicity.- 1.3. A Family of Serine Esterases Localized in Lymphocyte Granules.- 1.4. Proteoglycans.- 1.5. Leukalexins and Cytokines Related to Tumor Necrosis Factor and Lymphotoxin.- 2. Other Candidate Mechanisms of Lymphocyte-Mediated Killing.- 3. Resistance of Lymphocytes to Self-Mediated Killing.- 4. Conclusion.- 5. References.- 7 CR1-Cytoskeleton Interactions in Neutrophils.- 1. Introduction.- 2. Detergent Extraction of Cells.- 3. Receptor-Cytoskeleton Interactions.- 4. The C3b Receptor (CR1).- 5. References.- 8 The Flow of Granular Organelles in Leukocyte Differentiation.- 1. Introduction.- 2. Biogenesis of Membrane-Bound Organelles.- 2.1. Introduction.- 2.2. Endoplasmic Reticulum.- 2.3. Golgi Complex.- 2.4. Lysosomes.- 2.5. Communication between Compartments: Endosomes.- 2.6. Secretory Granules.- 3. Leukocyte Granules are Major Determinants of Function.- 3.1. Neutrophils.- 3.2. Platelets.- 3.3. Cytotoxic Lymphocytes.- 4. Granules Interact with the Plasma Membrane.- 4.1. Neutrophils.- 4.2. Platelets.- 5. Pathology of Myeloid Granules and Plasma Membranes.- 5.1. Nonneoplastic.- 5.2. Leukemic.- 6. Conclusion.- 7. References.- 9 The Elusive Oxidase: The Respiratory Burst Oxidase of Human Phagocytes...

This book focuses on how obesity and sedentary lifestyles adversely affect cancer risk and survival for individuals as well as mechanisms that may underlie those associations. However, evidence is accumulating rapidly on the cost of obesity and sedentary lifestyles to society. For example, obesity is estimated to lead to costs of $147 billion in the US.6 While research on individual level interventions for weight loss and increasing physical activity have identified efficacious approaches, these changes in behavior are not maintained by many in the current environments in the US and worldwide that promote weight gain and inactivity. Research on environmental and policy approaches for addressing these problems at the societal level is needed7, 8 and is a major component of the President's Report on Childhood Obesity released in April 2010. The epidemic of overweight and obesity and the increasing sedentary lifestyles will impact the magnitude and quality of the cancer problem globally. Increasing the knowledge of scientists, clinicians, and policy experts will aid in defining new prevention and treatment methods, to reduce the impact of energy balance on cancer, with the goal to eventually reduce the burden of cancer. Hopefully, this knowledge can be translated into incentives for the general public, persons at high risk, and cancer patients and survivors to increase physical activity, reduce excess weight, and maintain energy balance lifelong.

This volume presents the most current reviews on how cancer stem cells (CSCs) hypothesis dictates that the continued proliferation of a tumor is dependent on a sub-population of self-renewing and asymmetrically dividing neoplastic stem cells that supply a largely differentiated tumor. This volume provides a comprehensive overview of the characteristics of CSCs, their role in central nervous system (CNS) tumors, and the recent CSC-specific treatment modalities being used. The emerging focus on CSCs in brain tumors represents a paradigm shift in our understanding of the pathogenesis of these neoplasms. Importantly, the realization that a distinct sub-population of cells contributes disproportionately to the growth and sustenance of central nervous system tumors has important implications for the treatment of such tumors. To treat CNS tumors, there is now a growing need to treat CSCs to achieve adequate tumor control.

This volume is based on the Workshop on Systems Biology of Tumor Dormancy meeting, held July 25th to July 28th, 2011. The first annual CCSB workshop brought together biologists, clinicians, mathematicians, and computer scientists to discuss various aspects of tumor dormancy and develop novel mathematical/computational models with the keynote speakers. Specific topics included the angiogenic switch, immune system interactions, cancer stem cells and signaling.

Research over the past decades has firmly established the genetic basis of cancer. In particular, studies on animal tumour viruses and chromosome rearrangements in human tumours have concurred to identify so-called 'proto-oncogenes' and 'tumour suppressor genes', whose deregulation promotes carcinogenesis. These important findings not only explain the occurrence of certain hereditary tumours, but they also set the stage for the development of anti-cancer drugs that specifically target activated oncogenes. However, in spite of tremendous progress towards the elucidation of key signalling pathways involved in carcinogenesis, most cancers continue to elude currently available therapies. This stands as a reminder that "cancer" is an extraordinarily complex disease: although some cancers of the haematopoietic system show only a limited number of characteristic chromosomal aberrations, most solid tumours display a myriad of genetic changes and considerable genetic heterogeneity. This is thought to reflect a trait commonly referred to as 'genome instability', so that no two cancers are ever likely to display the exact same genetic alterations. Numerical and structural chromosome aberrations were recognised as a hallmark of human tumours for more than a century. Yet, the causes and consequences of these aberrations still remain to be fully understood. In particular, the question of how genome instability impacts on the development of human cancers continues to evoke intense debate.

In Hormone Therapy in Breast and Prostate Cancer, many of today's leading researchers and clinicians describe the principles underlying targeted hormonal treatments, assess the actions of new and established agents, and illustrate the new applications of hormonal chemoprevention for breast cancer. Topics range from preclinical and clinical antiestrogens to the inhibition of estrogen synthesis and the effects of androgen withdrawal. A wide variety of proven and new agents are discussed-antiestrogens, including aromatase inhibitors (anastrozole, letrozole, and others), SERMs (tamoxifen, raloxifene, and others), and such antiandrogenic strategies as goserelin and bicalutamide.

For the past decade or so, research regarding women's health has become a major source of concern among health professionals. Due to the vast amounts of research, it has been difficult to amass a comprehensive source describing the challenges of physicians in this area of medical treatment and care. The Handbook of Research on Oncological and Endoscopical Dilemmas in Modern Gynecological Clinical Practice is a pivotal reference source that provides vital research on the application of clinical practices in regards to the health of women and prevention of severe, life-threatening diseases. While highlighting topics such as mental health, women's health, and preventative care, this publication provides an insight into critical dilemmas and issues in modern gynecologic oncology and endoscopy as well as the methods of daily clinical practice. This book is ideally designed for obstetricians, gynecologists, specialized physicians, medical professionals, academicians, researchers, and medical students.

Cancer and Pregnancy covers the clinical challenges to diagnosing and treating malignancies in the pregnant patient; however, the book also shows how an understanding of the common features of both processes (rapid cell proliferation) may lead to novel anti-cancer treatment options. The book should be read by obstetricians and gynaecologists, clinical oncologists, reproduction specialists, and those involved in investigation of development, biology, toxicology, immunology, as well as cancer research.

Revealing essential roles of the tumor microenvironment in cancer progression, this book provides a comprehensive overview of the latest research in the field. A variety of topics are covered, including metabolism in the tumor microenvironment, stellate cells and endothelial progenitors in the tumor microenvironment, as well as the effects of HIV, viral hepatitis, and inflammation in the tumor microenvironment, and more. Taken alongside its companion volumes, Tumor Microenvironment: State of the Science updates us on what we know about various aspects of the tumor microenvironment, as well as future directions. This book is essential reading for advanced cell biology and cancer biology students as well as researchers seeking an update on research in the tumor microenvironment.

The aim of Apoptosis and Cancer is to describe the performance of contemporary techniques for studying the biology of apoptosis and its role in cancer. The protocols described will aid both the academic laboratory interested in further characterizing the mechanisms of apoptosis, as well as the industry laboratory, aimed at identifying new target molecules or screening for new compounds with potential clinical use.

This book focuses on issues in clinical practice and research that are of general interest. The articles primarily focus on understanding the pathogenic mechanisms of diseases, their prevention, and therapy. The topics addressed include cardiovascular regulation with regard to blood pressure and heart rate variability, and to coupling blood pressure changes with subarachnoid fluid oscillations. In addition, the book discusses recent advances in the diagnostics of and targeted molecular therapy for renal and pancreatic malignancies, growth disorders, vitamin D and calcium homeostasis in children in the context of neonatal urolithiasis, and neurosurgical interventions in multifarious age-related diseases of the vertebrae. Neuropsychological aspects of patients' quality of life and of shaping medical staff's attitude toward patients are also addressed. The respective articles are intended to build a bridge between basic and clinical research. Further, the book enhances the current body of knowledge on diagnostics and patient treatment and offers valuable new perspectives on practical clinical issues. As such, it offers a unique resource for clinicians, family physicians, medical scholars, and professionals engaged in patient management.

Image synthesis across and within medical imaging modalities is an active area of research with broad applications in radiology and radiation oncology. This book covers the principles and methods of medical image synthesis, along with state-of-the-art research. First, various traditional non-learning-based, traditional machine-learning-based, and recent deep-learning-based medical image synthesis methods are reviewed. Second, specific applications of different inter- and intra-modality image synthesis tasks and of synthetic image-aided segmentation and registration are introduced and summarized, listing and highlighting the proposed methods, study designs, and reported performances with the related clinical applications of representative studies. Third, the clinical usages of medical image synthesis, such as treatment planning and image-guided adaptive radiotherapy, are discussed. Last, the limitations and current challenges of various medical synthesis applications are explored, along with future trends and potential solutions to solve these difficulties. The benefits of medical image synthesis have sparked growing interest in a number of advanced clinical applications, such as magnetic resonance imaging (MRI)-only radiation therapy treatment planning and positron emission tomography (PET)/MRI scanning. This book will be a comprehensive and exciting resource for undergraduates, graduates, researchers, and practitioners.

Where do you begin to look for a recent, authoritative article on the diagnosis or management of a particular malignancy? The few general oncology text books are generally out of date. Single papers in specialized journal are informative but seldom comprehensive; these are more often preliminary reports on a very limited number of patients. Certain general journals frequently publish good in-depth reviews of cancer topics, and published symposium lectures are often the best overviews available. Unfortunately, these reviews and supplements appear sporadically, and the reader can never be sure when a topic of special interest will be covered. Cancer Treatment and Research is a series of authoritative volumes that aim to meet this need. It is an attempt to establish a critical mass ofoncology literature covering virtually all oncology topics, revised frequently to keep the coverage up to date, and easily available on a single library shelfor by a single personal subscription. We have approached the problem in the following fashion: first, by dividing the oncology literature into specific subdivisions such as lung cancer, genitourinary cancer, pediatric oncology, etc.;and second, by asking eminent authorities in each of these areas to edit a volume on the specific topic on an annual or biannual basis. Each topic and tumor type is covered in a volume appearing frequently and predictably, discussing current diagnosis, staging, markers, all forms of treatment modalities, basic biology, and more."

The Etiology and Prevention of Aerodigestive Tract Cancers.- Epidemiology of Vitamin A and Aerodigestive Cancer.- Multiple Primary Squamous Carcinomas of the Upper Aerodigestive Tract.- Genetic and Environmental Interactions as Risks for Aerodigestive Cancers.- Alcohol: A Cocarcinogen in Head and Neck Malignancies.- Smokeless Tobacco and Aerodigestive Tract Cancers: Recent Research Directions.- Biologic Markers as Predictors of Risk in Aerodigestive Tract Cancers.- Hamster Lung Cancer Model of Carcinogenesis and Chemoprevention.- The Hamster Cheek Pouch Model of Carcinogenesis and Chemoprevention.- Culture Conditions Affect Expression of the ?6?4 Integrin Associated with Aggressive Behavior in Head and Neck Cancer.- Growth Factors and Other Targets for Rational Application as Intervention Agents.- Hyperplasia and Squamous Metaplasia in the Tracheobronchial Epithelium: Alterations in the Balance of Growth and Differentiation Factors.- Micronuclei as Intermediate End Points in Intervention.- Study Design for the Prevention of Aerodigestive Tract Cancers.- Participant Enrollment, Participation, and Compliance in Chemoprevention Trials.- A Population-based Trial of ?-Carotene Chemoprevention of Head and Neck Cancer.- Chemoprevention of Barrett's Esophagus and Oral Leukoplakia.- Carotene and Retinol Efficacy Trial: Lung Cancer Chemoprevention Trial in Heavy Cigarette Smokers and Asbestos-exposed Workers.- An Intervention Trial in High-Risk Asbestos-exposed Persons.- Chemoprevention-of Aerodigestive Epithelial Cancers.- Contributors.

Proceedings of the 5th Biannual International Meeting on Angiogenesis: From the Molecular to Integrative Pharmacology, held July 1-7, 1999, in Crete, Greece. Angiogenesis, as a vastly complex biological process, has challenged researchers from all basic scientific disciplines, including pharmacology, biochemistry, physiology, embryology and anatomy. The significance of this phenomenon for the study of disease states has also interested clinicians from a number of specialist fields. This multidisciplinary work reflects the growth of awareness of concepts such as angiogenesis based therapy, the enormous therapeutic and commercial potential of which has attracted major research and investment in recent years. This volume, which aims to bridge the gap between basic and clinical methodology and understanding, presents the most up-to-date developments in this field.

Health has been conceptualized by world and national health organizations (WHO, CDC, Healthy People 2010) as more than the absence of disease. It involves a focus on physical, psychosocial, and functional aspects of life as well as the prevention of future illnesses. At this point in the development of quality health care for cancer survivors, there is sufficient knowledge and expert opinion to push efforts forward to improve the health of cancer survivors. Clearly there is more research in the most prevalent forms of cancers (e.g., breast cancer) than others that provide us with guidance on how to optimize their health, but there are data on other forms of cancers that can also better inform practice. There may also be general care practices that can cut across cancer types. There has been an emergence of epidemiological and clinical research in cancer survivors that can form the basis for a revolution in the quality and nature of health care that survivors receive. This book not only provides the reader with diverse perspectives and data but also integrates this information so it can serve as the foundation necessary to improve and maintain the health of cancer survivors. Reporting of symptoms to health care providers is a complex, multi-determined problem influenced not only by the pathophysiology but also, as we have learned over the years through pain research, by societal, cultural, and biobehavioral factors. This book will consider this important aspect of follow-up for millions of cancer survivors because of the strong reliance on symptom reporting for clinical decision making. In order for us to generate meaningful and effective treatment, we need to better understand the symptom experience in cancer survivors. This book provides much information that will assist us to better understand and manage this complicated end point. The presenting problems need to be articulated and "conceptualized" as clearly as possible by both parties so appropriate actions can be taken. Since health care costs are a major concern for patients, payers, and providers, this area will also be addressed in all the relevant sections. In taking an interdisciplinary perspective, this book illustrates the importance of a team approach to the improvement of health care and associated health, well-being, and functioning in cancer survivors. The 17 chapters cover critical topics of which physicians and providers of all types must be aware in order to provide the most comprehensive and responsive care for cancer survivors. All of the clinical care chapters include case studies to illustrate the real-world application of these approaches in cancer survivors. Information about sources of referral both within and outside the traditional health care communities will be provided in tabular form. There is no other text that provides both an overview of the problems and their challenges, case illustrations of direct application, and the reality of reimbursement for such care. The editors hope that there may be no need for the clinician or the survivor to adapt to a "new normal" if the presenting problems are understood and handled from an interdisciplinary perspective as outlined here.