There is no doubt that the advent of immunocytochemical techniques, by enhancing our ability to detect specific cell products or markers, has opened new avenues in the understanding of human diseases, and in our ability to perform better diagnosis in surgical pathology. The rapid development of this field has resulted in thousands of publications in the literature regarding immunocytochemistry in diagnostic pathology. This explosion of knowledge makes necessary publications summarizing what are the main markers available and how they can be used in the diagnosis of tumors. The need of a more organized and structured knowledge was evident during the workshop in Immunocytochemistry of Tumor Diagnosis that took place in the City of Detroit an October 1984. This book is the result of that workshop in which 22 chapters are focusing an the main subject of differential diagnosis of tumors. Jose Russo, M.D. Editor xiii ACKNOWLEDGEMENTS I wish to thank my many associates at the Michigan Cancer Foundation for their help in the preparation of this manuscript. I give thanks to Dr.

Tumor necrosis factor (TNF)-? is a pleiotropic cytokine involved in a va- ety of physiological and pathological processes. After initial discovery of its ability to induce cell death and animal cachexia, it was soon realized that this cytokine played pivotal roles in the regulation of homeostasis and inflam- tory-immune responses. This led to an explosion of interest in basic and tra- lational research activities on the role of TNF in many diseases, such as cancer, septic shock, rheumatoid arthritis, and infectious diseases of the central n- vous system. Because of its potential therapeutic value, many academic and industrial research groups have worked to discover compounds that can block its activity. These studies have led to the approval of anti-TNF antibodies and soluble TNF receptors for the therapy of rheumatoid arthritis and Crohn's d- ease. TNF also can be an attractive anticancer agent capable of damaging tum- associated vessels and of inducing tumor necrosis in patients. The unique properties of TNF have led to its registration as a drug for locoregional tre- ment of sarcomas of the extremities, and stimulated many preclinical studies aimed at improving its therapeutic index for systemic use. Tumor Necrosis Factor: Methods and Protocols provides an overview of basic and translational research along with a series of practical procedures on TNF production, characterization, mutagenesis, detection in biological spe- mens, as well as several in vitro assays and animal models for studying the role of TNF in various diseases.

The book provides a comprehensive overview of the current state, and the new concepts for the future directions of modern cancer therapy. Bringing together all the relevant aspects from basic and applied science, and the clinical experiences of this new direction in medicine, it is an up-to-date summary of the activities in the field and will be the basis for evaluating future progress in this area.

Folate pathways are essential in metabolism and macromolecule synthesis. Antifolate drugs that are largely transported via a high capacity folate transporter (i.e. the reduced-folate carrier) and inhibit folate-dependent enzymes include the dihydrofolate reductase inhibitor, methotrexate, and the thymidylate synthase inhibitors, raltitrexed and pemetrexed. Major advances in folate research made within the last decade include (i) the approval of pemetrexed for the treatment of lung cancer and mesothelioma, and (ii) the demonstration that cell membrane-anchored folate receptors (FR) are exploitable for cancer and inflammatory disease management. FRs are not widely distributed in normal tissues, except on some luminal surfaces; however, they are accessible to systemically administered agents when expressed on many cancers as well as on activated macrophages involved in various inflammatory diseases. High affinity folate-radioisotope conjugates have been developed for imaging pathogenic FR-positive diseases, including cancer. Since the FR transports folates via a low capacity but high affinity endocytic pathway, a variety of FR-targeted antifolate drugs and folate conjugates bearing a wide range of payloads (including cytotoxic drugs) are currently being developed which exploit this property. The FR is also being utilized in immunotherapy approaches for the treatment of overexpressing cancers.

This sixth volume in the series Methods of Cancer Diagnosis, Therapy, and Prognosis discusses Ovarian Cancer, Renal Cancer, Urogenitary Cancer, Urinary Bladder Cancer, Cervical Uterine Cancer, Skin Cancer, Leukemia, Multiple Myeloma and Sarcoma. Both standard and emerging therapies for these cancers, written by expert oncologists/pathologists in this field, are included. This fully illustrated volume Identifies biomarkers based on genetic alterations for clear cell ovarian adenocarcinoma. Identifies subgroups of ovarian cancer by using differential gene expression. Includes the application of the power-Doppler imaging for distinguishing benign from malignant complex adrenal masses in ovarian cancer. Emphasizes the advantage of using cytoreduction surgery for diagnosing advanced ovarian cancer. Provides details on the treatment of kidney cancer with radiofrequency ablation, surgery, and chemotherapy. Explains the use of immunohistochemistry for diagnosing adenomatoid tumor of the adrenal gland. Discusses the chemotherapy of testicular cancer and related second primary tumors. Includes the diagnosis of urothelial bladder cancer with urine-based tumor markers. Explains the use of immunohistochemistry and MRI for diagnosing uterine cervical cancer and describes the staging of this cancer using PET alone or PET/CT. Describes the localization of malignant melanoma using FDG-PET/CT. Explains the use of prognostic receptors for nonmelanoma skin cancer. Details the treatment of multiple myeloma using immunotherapy, radiotherapy, and targeted radionuclide therapy. Presents diagnostic immunohistochemistry of synovial and Kaposi's sarcoma. The technological advances presented in this volume are expected to expedite new discoveries and their translation to clinical practice. The field of oncology will benefit the most from these advanced methods, as a combination of therapies and personalized medicine will improve early detection of thes

Psychosocial Resource Variables in Cancer Studies reviews the literature on selected psychosocial resource variables in cancer in order to raise and examine conceptual and methodological issues and to offer suggestions for future directions in the field. It provides investigators and clinicians with a systematic treatment of the state of the art in research on specific resource factors and provides a careful consideration of more generic methodological and statistical issues in this research context.Editors Curbow and Somerfield define resources as aspects of a person or environment that are brought to bear on the maintenance or restoration of adaptation under taxing conditions. They hope Psychosocial Resource Variables in Cancer Studies is just the beginning of an ongoing discussion within the field of psychosocial oncology on the nature and use of resource variables. The book's topics are crucial since researchers appear to be committed to using resource variables to explain outcomes. Also, resource variables are increasingly considered as explanatory concepts in quality-of-life research.Psychosocial Resource Variables in Cancer Studies offers critical reviews of the major resource variables investigated in contemporary psychosocial oncology research. It provides timely information on vital issues in this research, emphasizing studies of the influence of personal and social resources on adaptation to cancer. Chapters cover topics such as: the use of resource variables in the explanation of individual differences in adaptation to cancer and cancer treatment theories, measures, and methodological issues in the use of perceived control the use of the transactional model of coping to examine issues surrounding coping and the management of cancer demands religion and spirituality as resources in coping with cancer social support in adaptation to cancer and survival the clinical usefulness of research on psychosocial resources major measures of psychological functioning in psychosocial oncology research statistical and analytical issues in the use of resource variables roles of qualitative and quantitative approaches in exploring resource variablesThe editors begin with an overview of the oncology field and offer comments on issues that can be generalized to all psychosocial resource variables. Next is a presentation of a series of review papers on selected resource variables, including perceived control, coping, religion and spirituality, and social support, followed by a discussion of the clinical utility of research on these resource variables. The book concludes with a discussion of important cross-cutting methodological issues, including the selection of psychological functioning outcome measures, the statistical analysis of resource variables, and quantitative versus qualitative approaches.Psychosocial Reource Variables in Cancer is a valuable reference and guide for health psychologists, clinical health psychologists, clinical social workers in oncology, medical sociologists, medical anthropologists, and oncology nurses. It may also serve as important reading material for courses in health psychology, physiological factors in health and illness, personality and diseases, and stress and coping.

In recent years, increasing evidence has suggested that abnormal activation of signaling pathways is a critical event in cancer pathogenesis. In particular, activation of these pathways can lead to inappropriate cellular survival, proliferation, pluripotency, invasion, metastasis, and angiogenesis. Thus, understanding the mechanisms by which signaling pathways become subverted in a cancer cell can provide insight into critical events in cancer pathogenesis. Furthermore, as our ability to target specific molecular interactions advances, we now have the ability to design small molecules, protein therapeutics, and other forms of targeted therapies. By focusing on the specific molecular abnormalities in a cancer cell, these agents hold the potential to be much more effective and much less toxic than current cytotoxic therapies.

Because of its relative rarity and favorable outcome, it has not been feasible to assess medical interventions for thyroid cancer using randomized prospective trials. The approach to diagnosis and treatment relies to a great extent on information derived from retrospective studies. Overall prognosis and survival rates have been edging upward over the past two decades. This is attributed to a wider acceptance of total thyroidectomy as the primary surgical strategy. The appropriate indication of radioiodine therapy remains controversial, and physicians must be familiar with staging criteria to make educated decisions. We are now beginning to understand the genetic mechanisms of thyroid tumor initiation and progression. There are still major challenges ahead. Thyroid Cancer provides comprehensive updates on the epidemiology, pathogenesis, diagnosis and treatment of thyroid neoplasms. Although the material should be of particular interest to scholars in the field, the contributors have striven to make it of practical use to physicians who treat patients with thyroid disease.

Traces the history of the study of tumor viruses and its role in driving breakthroughs in cancer research. Worldwide, approximately one-fifth of human cancers are caused by tumor viruses, with hepatitis B virus and HPV being the leading culprits. While the explosive growth in molecular biology in the late twentieth century is well known, the role that the study of tumor viruses has played in driving many of the greatest breakthroughs is not. Without the insights gained by studying tumor viruses, many significant theoretical advancements over the last four decades in cellular and molecular biology would not have been made. More practically, the study of tumor viruses has saved thousands, if not millions, of lives. In Cancer Virus Hunters, Gregory J. Morgan traces the high points in the development of tumor virology, from Peyton Rous's pioneering work on chicken tumors in 1909 to the successful development of an HPV vaccine for cervical cancer in 2006. Morgan offers a novel approach to understanding the interconnectedness of a long series of biomedical breakthroughs, including those that led to seven Nobel prizes. Among other advances, Morgan describes and contextualizes the science that prompted the discoveries of reverse transcriptase, RNA splicing, the tumor suppressor p53, the vaccine for hepatitis B, and the HIV test. He also explores how "cancer virus hunters" have demonstrated the virtue of beginning with a simple system, even when investigating a complex disease like cancer. Based on extensive archival research and over fifty interviews with experts, Cancer Virus Hunters is a tour de force summarizing a century of research to show how discoveries made with tumor viruses came to dominate the contemporary understanding of cancer. By showcasing the scientists themselves, the book makes for an unusually accessible journey through the history of science. It will be of interest to biomedical professionals-especially in oncology, hepatology, and infectious disease-in addition to historians of science and anyone interested in cancer research.

In recent years, serine proteases and matrix metalloproteinases (MMPs) have gained considerable attention in tumor biology. For most of these proteases, their expression is a reliable indication of ongoing tissue remodeling. This book provides a comprehensive evaluation of the mechanisms of action of proteases and their inhibitors in tumor biology. The first part provides the reader with a selective overview of the molecular biology of serine proteases, MMPs and their physiological inhibitors. The most important proteases and their physiological as well as synthetic inhibitors are evaluated in the most relevant models of experimental and human cancer. The clinical aspects are also taken into account.
This volume offers an update on this challenging aspect of cancer treatment, its interest bias, and possible clinical implication.

Rapid progress has been made in our understanding of the molecular mechanisms of cell growth and oncogenesis during the past decade. This book comprises recent results on the regulation of cell growth in normal and neoplastic tissues by growth factors including hormones, and by the activation and inactivation of oncogenes and tumor suppressor genes, respectively. Special attention has been given to the presentation of the frequently neglected close correlation between changes in signal transduction and metabolism pathways during oncogenesis.

Patients with a variety of tumors present to the physician because of clinical manifestations of hormones secreted in excess. This phenomenon attracted the investigative interest of such pioneers as Harvey Cushing who recognized that pituitary tumors may cause acromegaly and Charles Mayo who associated hyper tension with adrenal medullary neoplasms. Current int rest in endocrine-related tumors has intensified because of the explosive development of newer methodol ogy for their study. Specific measurements of secretory products, hybridization assays to identify products of genomic translation and quantitative assessment of tissue hormone receptors have provided means of characterizing and precisely following patients with endocrine-related tumors. Treatments based upon these advances are rapidly proliferating. The current volume attempts to synthesize much of this recent information with the goal of providing a sound basis for making clinical judgements regarding diagnosis and management. Tumors of endocrine glandular tissues commonly confront practicing physi cians with difficult management problems. Several unique features of these tumors necessitate collaboration among various specialty disciplines in order to resolve these problems and to provide a high level of clinical care. For example, endocrine neoplasms secrete active hormones or hormone precursors which produce clinical manifestations most familiar to endocrinologists. Certain thera pies such as radioactive iodine for thyroid cancer take advantage of the hormone responsiveness of these tumors to facilitate treatment. These aspects require individuals trained in endocrinology to implement complex diagnostic and thera peutic maneuvers."

This book describes all human leukemia-lymphoma cell lines that have been established and that grow continuously under standardised in vitro conditions. These lines are derived from cells belonging to all the major hematopoietic cell lineages, i.e. B- and T-lymphocytes, natural killer cells, granulocytic cells and megakaryocytic cells. The clinical data, the culture conditions and the major phenotypic features of the cell lines are described with citations. This book is the first book describing human leukemia-lymphoma cell lines and will be of interest to scientists involved in the areas of hematology, oncology, immunology, molecular biology and cytogenetics. Cancer Cell Lines, Volumes 1-3: These 3 volumes provide a comprehensive text on the culture of established cell lines from every type of human cancer. The volumes provide a basic manual and reference resource for every cancer research scientist using human cancer cells.

Cancer is the leading cause of death in the United States. The improvement of screening procedures and treatments have led to higher survival rates, and consequently to an increased number of individuals who fear that their cancer might come back. Fear of cancer recurrence (FCR) is defined as the fear, worry, or concern that cancer may come back or progress. FCR has been found to be the number one unmet need of cancer survivors. High levels of FCR are associated with greater psychological distress, impaired functioning, decreased quality of life, and increased medical consultations, psychotropic usage and health-care costs. It is therefore crucial to offer these patients an appropriate and effective treatment. The books first propose a theoretical model of FCR that identifies the five main targets of intervention in this program: 1) cognitive interpretation; 2) behavioural avoidance; 3) cognitive avoidance; 4) reassurance and control seeking; 5) intolerance of uncertainty. Then, each target is discussed and specific cognitive-behavioural therapy strategies are suggested that focus on each of them based on the best available empirical evidence for the treatment of anxiety disorders (e.g., generalized anxiety disorder) and cancer-related anxiety. This book will be of interest to clinicians working with cancer patients such as psychologists and other health care providers as well as cancer patients and survivors. Graduate students in clinical health psychology, and connecting disciplines such as psycho-oncology, psychiatry, nursing, social work, rehabilitation, spiritual care, and sexology might also find this text of value.

A comprehensive review of the use of global gene expression profiling to understand human tumors. The authors focus on the analysis of human tissue samples for a variety of cancers, including breast, colorectal, lung, renal, ovarian, bone, and brain tumors, among others. A primer on the technology and its novel analytical methods. Contains over 40 color images. Explains both the theory and practice of comprehensive gene expression profiling. Timely and topical, Expression Profiling of Human Tumors: Diagnostic and Research Applications offers every oncologist, pathologists, and cancer surgeons an essential introduction to the most promising new high-throughput investigative approaches in molecular biology-technology that is already dramatically reshaping the future of cancer research, diagnostic pathology, and clinical oncology.

This book, written by world-leading p53 researchers including many of those who have shaped the field over the past 25 years, provides unique insights into the progress of the p53 field and the prospects for better cancer diagnosis and therapy in the future. It should be of interest to everybody working in cancer research, clinical oncology, and molecular biology, and indeed to anybody interested in science, medicine, as well as in recent developments of the ideas and concepts of the molecular biology of cancer.

Introduction The prevailing model of medical care for patients with cancer emphasizes the curative efforts of medical technology toward the eradication of the disease. Yet the suffering of the patient as a result of both the disease and our efforts to treat it is often overlooked. If we are to improve the survival of patients with cancer, it will be through intensive research into the molecular under pinnings of the disease and clinical trials of new therapies. However, it is essen tial to recognize and address the suffering of cancer patients as they are being treated. It is the purpose of this book to illuminate and advance the preven tion and treatment of suffering as part of the continuum of care for patients with cancer. Fundamental concepts Since the time of Hippocrates in the fifth century B.c., there have been two overall goals for the physician: * Cure of disease * Relief of suffering From our vantage point in the late twentieth century looking back at previ ous centuries, it is easy to observe that, aside from surgery, much of the medical care administered to patients with cancer was aimed at relieving the suffering associated with illness. It wasn't until the concept of disease (as opposed to illness) was elucidated and the scientific method was applied to understand ing and eradicating cancer that significant strides were made to improve the physician's ability to cure cancer.

Encyclopedia of Cancer, Third Edition, Three Volume Set provides a comprehensive, up-to-date overview of the multiple facets of the disease, including research, treatment and societal impact. This new edition comprises 180 contributions from renown experts who present the latest in Mechanisms, Hallmarks of Cancer, Causes of Cancer, Prevention and Control, Diagnosis and Therapy, Pathology and the Genetics of specific Cancers. Readers will find a comprehensive overview of the main areas of oncology, including etiology, mechanisms, prevention, and treatments, from basic science to clinical applications and public health, all set alongside the latest advances and hot topics that have emerged since the previous edition. Topics of interest in the field, including genomics and epigenomics, our understanding of the causes of cancer and the approaches to preventing it (e.g., HPV vaccination, role of obesity and nutrition, molecular markers of environmental exposures), new screening techniques (e.g., low-dose CT for lung cancer) and improvements in the treatment of many cancers (e.g., breast cancer, lung adenocarcinoma) are comprehensively and authoritatively presented.

A "brilliant" ("Fortune"), eye-opening history of the war on cancer, "The Truth in Small Doses" asks why we are losing this essential fight and charts a path forward.
Over the past half century, deaths from heart disease, stroke, and so many other killers have fallen dramatically. But cancer continues to kill with abandon. In 2013, despite a four-decade "war" against the disease that has cost hundreds of billions of dollars, more than 1.6 million Americans will be diagnosed with cancer and nearly six hundred thousand will die from it.
A decade ago, Clifton Leaf, a celebrated journalist and a cancer survivor himself, began to investigate why we had made such limited progress fighting this terrifying disease. The result is a gripping narrative that reveals why the public's immense investment in research has been badly misspent, why scientists seldom collaborate and share their data, why new drugs are so expensive yet routinely fail, and why our best hope for progress--brilliant young scientists--are now abandoning the search for a cure. "Through flowing prose Leaf delivers, alongside facts and data, stories on personalities involved in research, the fascinating process of solving an unusual and highly deadly cancer in Africa, and the heartbreaking realities of cancer treatment in children today. Leaf's extensively investigated treatise will resonate with researchers and patients frustrated by the bureaucratic woes he delineates. Public policy makers, grant reviewers, and pharmaceutical researchers alike must consider Leaf's indictment and proposed solutions" ("Publishers Weekly"). "The Truth in Small Doses" is that rare tale that will both outrage readers and inspire conversation and change.

Representing the most relevant procedures and technologies aiding the advance of the field of HPV-mediated carcinogenesis of the cervix and other anatomical regions of squamocolumnar transition, such as the anorectum, penis, and oropharynx, Cervical Cancer: Methods and Protocols compiles a detailed collection of practical chapters. The first half of the book covers HPV types, pathogenesis of cervical cancer (CxCA), prevention, and novel potential drug targets, while the second half explores pathology, genomics, modeling of CxCA, and experimental therapeutic strategies. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and vital, Cervical Cancer: Methods and Protocols serves as a valuable resource to both bench scientists and clinicians who step into the realm of high-risk HPVs and CxCA for the first time or those who wish to learn novel approaches or expand their toolbox for the study of CxCA.

Liver-Directed Therapy for Primary and Metastatic Liver Tumors is a comprehensive examination of tumors of the liver. It provides a unique multi-modality approach to management of all types of primary and secondary liver tumors. The biology of liver cancers, state of the art radiologic imaging and novel, non-surgical interventional strategies are given. There is an in depth analysis of surgical options including transplantation, resection, interstitial ablation techniques and liver-directed chemotherapy for hepatocellular carcinoma, bile duct cancers, and colorectal and neuroendocrine liver metastases. Because of the unique and comprehensive examination of liver tumors, this work is an excellent resource for surgical, transplant and medical oncologists, surgeons, gastroenterologists, and radiologists.

The average physician and even cancer care-givers are not knowledgeable about the effects of cancer treatment on sex and reproductive life. They are even less aware of the options available for treatment of such patients. "Cancer and Sexual Health" fills a great need for a reference work devoted to the link between cancer and human sexuality. The volume is designed to give a comprehensive and state-of-the-art review of the sexual and reproductive consequences of cancer diagnosis and treatment. It will prove an invaluable resource for those clinicians caring for cancer patients as well as acting as a reference text for the sexual medicine clinician who may not see a large number of cancer patients.

PI3K has become a very intense area of research, with over 2000 publications on PI3K in PubMed for 2009 alone. The expectations for a therapeutic impact of intervention with PI3K activity are high, and progress in the clinical arena is being monitored by many. However, targeted therapies almost invariably encounter roadblocks, often exposing unresolved questions in the basic understanding of the target

Being diagnosed with cancer is devastating. But when the cancer cells have to spread to form secondary colonies, the prognosis for the patient is worse. If meaningful improvements in survival are to occur, then control of metastasis will be a foundation. Relatively little is known about the control of the metastatic process at the molecular level. This volume begins to explore our current knowledge regarding the underlying molecular and biochemical mechanisms controlling the metastatic phenotype. While all of the authors attempted to put their findings into a context for translation to the clinical situation, the state-of-the-art does not fully allow this. Nonetheless, we write these summaries of our work as an early effort toward that end. I am grateful to all of the authors who have contributed generously of their time and energies to make this volume a reality. To metastasize, neoplastic cells dissociate from the primary tumor, enter a circulatory compartment (typically lymphatics or blood vasculature), survive transport, arrest, exit the circulation and finally proliferate at a discontinuous site in response to local growth factors. Unless cells accomplish every step of the metastatic cascade, metastases cannot develop. The process is highly inefficient, i. e. ,