This volume focuses on recent advances in understanding T cells as key players in antitumor immune responses, and as a result T cell-based immunotherapy is starting to transform the treatment of advanced cancers. However, despite recent successes, many patients with cancer fail to respond to these treatments. Defective migration of T cells into and within tumors is considered as an important resistance mechanism to cancer immunotherapy.The volume includes three sections. The first section covers general knowledge about T cell trafficking during a normal immune response but also during tumor development. The second section provides an in-depth description of the different obstacles that prevent T cells from migrating and contacting tumor cells. The third section explores therapeutic strategies to improve trafficking of T cells into tumors and, thus, to enhance the effectiveness of cancer immunotherapy.

To produce a comprehensive overview of macrophages and related cell types in a short review volume is an impossible task. When I selected the topics to be included, some equally important areas were omitted by necessity, and for this I apologize. My choices have been somewhat eclectic, touching subjects of personal interest (such as osteoclast biology and macrophage electrophysiology) or of current fashion (apopto sis, antigen processing, cell adhesion molecules). The book has also had to encompass areas of a more general flavor to provide balance for the general reader (such as reviews of macrophage development, heterogeneity, and function, and of the surface molecules expressed by macrophages). I thank all the authors for their prompt sub missions; all have been of high quality, and my editorial tasks, thankfully, have been minimal. Michael A. Horton London, United Kingdom ix Contents Chapter J An Overview of Receptors of MPS Cells lain Fraser and Siam on Gordon 1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. The Mononuclear Phagocyte System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 3. Diversity of Macrophage Plasma Membrane Receptors. . . . . . . . . . . . . . . . 6 3. 1 A Structural Approach to Classification . . . . . . . . . . . . . . . . . . . . . . . . . . 6 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 3. 2 Multisubunit Receptors 3. 3 Soluble Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 3. 4 Lectins and Lectin-Like Receptors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 4. Functions and Selected Examples. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 4. 1 Growth, Differentiation, and Modulation . . . . . . . . . . . . . . . . . . . . . . . . 14 4. 2 Cell-Cell and Cell-Matrix Interactions. . . . . . . . . . . . . . . . . . . . . . . . . . . 16 4. 3 Endocytosis and Scavenger Receptors. . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 4. 4 Secretory Responses and Biosynthesis of Effector Molecules . . . . . . 17 5. Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 6. References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 . . . . . . . . . . . . . . . . . . . ."

Hepatocellular Carcinoma: Targeted Therapy provides a detailed repository of the latest information regarding HCC epidemiology, diagnosis, imaging, pathology, staging, and treatment options. This volume also provides an up-to-date guide for treatment that explores not only traditional treatments, but newer investigational treatment options including, surgical resection, liver transplantation, ablation (radiofrequency, microwave), percutaneous ethanol or acetic acid injection, transarterial chemoembolization (TACE), intra-arterial radiation therapy, and systemic chemotherapy. Heptocellular Carcinoma: Targeted Therapy will be of great value to all health care professionals and trainees worldwide who have an interest in the diagnosis and treatment of HCC, including surgeons, medical oncologists, radiologists, radiation oncologists, and pathologists.

Where do you begin to look for a recent, authoritative article on the diagnosis or management of particular malignancy? The few general oncology text books are generally out of date. Single papers in specialized journals are informative but seldom comprehensive; these are more often preliminary reports on a very limited number of patients. Certain general journals fre quently publish good in-depth reviews of cancer topics, and published sym posium 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 which aim to meet this need. It is an attempt to establish a critical mass of oncology literature covering virtually all oncology topics, revised frequently to keep the coverage up to date, easily available on a single library shelf or by a single personal subscription. We have approached the problem in the following fashion. First, by divid ing the oncology literature into specific subdivisions such as lung cancer, genitourinary cancer, pediatric oncology, etc. 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 Hippo signaling pathway is rapidly gaining recognition as an important player in organ size control and tumorigenesis, and many leading scientists are showing increased interest in this growing field and it's relation to cancer. The chapters in this volume cover virtually all aspects of tumor biology, because members of the Hippo Pathway have been associated with numerous well-established cell signaling pathways, just to name a few; Ras, Wnt, TGFbeta and p53. Moreover, Hippo signaling is not solely involved in regulating "classic" tumor characteristics such as cell proliferation, survival and growth, but is also diversely involved in cell-autonomous and non-cell-autonomous differentiation, migration and organ size control. The primary audience are researchers interested in basic science in the areas of tumor suppression, cell cycle and size regulation, development and differentiation.

The subject matter of volume 2 of the 2-volumes-handbook focusses especially on rare sarcomas of the whole female genitalia. These entities include angiosarcoma, the different lipo- and rhabdomyosarcoma as well as newer entities like the PEComa. Furthermore, mixed mullerian tumors like the benign adenofibroma and the malignant adenosarcoma and carcinosarcoma are described in detail. The book provides a description at length of the epidemiology, etiology, pathological anatomy, prognosis, diagnosis, differential diagnosis, imaging and comprehensive therapy of each primary, relapsed, and metastasized tumor including surgery, chemo-, hormone- and radio- and targeted therapy. An own chapter is devoted to the problems of fertility and pregnancy in connection with all sarcomas, variants of leiomyoma, atypical smooth muscle tumors, disseminated peritoneal leiomyomatosis, benign metastasizing leiomyoma, intravenous leiomyomatosis and endometrial stromal tumors - endometrial stromal nodules, endometrial stromal tumor with sex cord-like elements (ESTSCLE), uterine tumor resembling ovarian sex-cord tumor (UTROSCT) -and all mixed tumors - of the female genitalia. The book aims to identify and provide diagnostic and therapeutic guidance. The listed tumor entities also constitute a particular diagnostic challenge for pathologists that contains numerous pitfalls and difficulties. This book, therefore, addresses gynecologists and pathologists in both clinical and private practice, but also surgeons and hemato-oncologists.

Over the past 30 years many significant advances have been made in the management of a number of disseminated malignant diseases. The prognosis for diseases such as childhood leukaemia, choriocarcinoma and Hodgkin's disease has gradually been transformed as better anti tumour agents have become available and their clinical use has been refined. During the past 10 years the advent of new agents, particularly cisplatin, bleomycin and the podophyllotoxins, has allowed the cure of disseminated testicular tumours. This degree of success has not, however, been achieved in the case of a number of other common cancers. Ovarian carcinoma is tantalisingly chemo-sensitive and although there are long term survivors from disseminated disease, these are only a small proportion of the total. Breast cancer, although "sensitive" to a multitude of drugs appears to have yielded neither survival benefit, nor cure to the efforts of therapists, while tumours such as those of the colon remain stubbornly unresponsive. Against this backcloth it is apparent that additional more selective treatments are needed if further impact is to be made on the problem of cancer. The development of such agents requires the integration of a multidisciplinary effort encompassing the fields of chemistry, biology and medicine. This symposium provided a forum for clinical and preclinical sCientists, where current aspects of cancer treatment were reviewed and approaches to the development of a new generation of more selective anticancer drugs discussed.

The present volume of Epigenetics and Human Health is devoted to the patho-epigenetics of viral and microbial infections, an exiting new field of disease-related epigenetic research. As recognized during the past years, epigenetic reprogramming of pathogen and host genome functions - the latter frequently induced by pathogens - plays an important role in many infectious processes. Beyond their immediate relevance for pathogen proliferation and obligatorily associated symptoms, such alterations frequently contribute to severe additional complications, such as the development of immunodeficiency, cancer and various chronic disorders. This holds in particular for epigenetic dysregulation of host gene expression induced by latent infections. The present book summarizes current knowledge of the mechanisms underlying epigenetic changes caused by viral, bacterial, fungal and protozoan infections and their impact on human health.

The emotional pressures on cancer patients and their families are increasing and traditional supports are decreasing. This book attempts to provide a readable, authoritative and balanced review of the emotional pressures and coping methods of cancer patients, and the help currently available to them. The special problems of children and terminal patients with cancer, and the role of the family in coping, are also examined. A balanced and critical assessment is made of defects in health organisation, training of personnel and attitudes to cancer patients in Western society. A similar assessment is made of the growing tendency to self help, mutual help and group activities for such patients. While each individual needs to select coping aids best suited to his or her own temperament, medical advisors need to make more time available for discussion of technical, emotional, social and sexual problems. The availability of a cancer-treating "team" makes this feasible. Chapters were invited from physicians, psychiatrists, psychologists and sociologists expert in this field, and they have responsed to the challenge of writing in non-technical language. This is so that readership can cross disciplinary boundaries and thus stimulate physicians, nurses, psychologists, sociologists, clergy and others, to satisfy some of the currently unmet needs of cancer patients. The reader may note a small amount of overlap between some chapters, permitted in order to maintain continuity and make each chapter complete in itself.

This volume highlights the most interesting biomedical and clinical applications of high-dimensional flow and mass cytometry. It reviews current practical approaches used to perform high-dimensional experiments and addresses key bioinformatic techniques for the analysis of data sets involving dozens of parameters in millions of single cells. Topics include single cell cancer biology; studies of the human immunome; exploration of immunological cell types such as CD8+ T cells; decipherment of signaling processes of cancer; mass-tag cellular barcoding; analysis of protein interactions by proximity ligation assays; Cytobank, a platform for the analysis of cytometry data; computational analysis of high-dimensional flow cytometric data; computational deconvolution approaches for the description of intracellular signaling dynamics and hyperspectral cytometry. All 10 chapters of this book have been written by respected experts in their fields. It is an invaluable reference book for both basic and clinical researchers.

Andrew Arnold The past several years have been a time of intense excitement and have brought major advances in the understanding and treatment of endocrine neoplasms. This is therefore an excellent point at which to undertake a broad based overview of the state of the art in endocrine neoplasia for the Cancer Treatment and Research series. Because of the wide and interdisciplinary readership of this series, our aim for each chapter has been to provide ample background for those not highly familiar with the topic, while emphasizing the most recent advances. Furthermore, the chapters have been written with the clinician in mind, whether she or he is an oncologist, endocrinologist, surgeon, generalist, pathologist, or radiologist. As such, the authors' mission has been to focus on clinically relevant issues and to present the scientific basis of current or potential future advances in a manner easily digestible to the nonexpert. Endocrine tumors often cause problems for the patient by virtue of their hormonal activity, which may frequently (but certainly not always) over shadow the adverse consequences related to their mass per se. In fact, it is important to keep in mind that endocrine tumors can manifest two biologically separable but often intertwined properties, namely, increased cell mass and abnormal hormonal function. These need not go hand in hand, and their distinction has definite clinical relevance in, for example, the increasingly recognized problem of incidentally discovered adrenal or pituitary masses."

When the first edition of this book published in 1994, the psychoimmunology of cancer was still emerging as a topic for serious scientific study. Now, less than ten years later, there is a huge quantity of academic literature about the relationships between psychological variables, the immune system and cancer growth, accompanied by a lively popular interest.

In this new edition leading specialists have provided broad critical reviews of the different aspects. Part I, which presents the biological background, will be of particular interest to those with technical knowledge of the relevant laboratory based disciplines. It covers mechanisms mediating the effects of psychological status in the immune system, and anti-cancer mechanisms involving the immune system. Part II is clinically orientated, and accessible to a wide audience. Whether psychotherapeutic interventions can help patients live longer, as well as coping better, is obviously the key question and several contributors consider the clinical evidence for this. A new, speculative chapter on the spiritual context of immunity and cancer has also been added.

The psychoimmunology of cancer involves many complex issues, understanding of which remains far from complete. However, the contributors, besides reviewing the current state of knowledge and the implications for cancer patients, offer predictions for the future and ideas about further research.

From reviews of the first edition:

'The chief quality of this book is its presentation of an excellent but critical overview of the entire range of what is today called 'psychoimmunology', and it is to be recommended to all who are interested in the subject.' Annals of Oncology

Cell growth, one of the most fundamental of biological processes, has long been among the least understood. On April 24-28, 1984 sci- entists convened from around the world in Canada's Banff National Park for The International Cell Cycle Society's 10th Conference. Their purpose was to evaluate recent developments in the field of cell prolif- eration and to explore the interrelationship between cell growth, de- velopment, and differentiation, and proliferative diseases such as can- cer. Growth, Cancer, and the Cell Cycle collects those conference papers that present the most recent advances in this field. The first section of the book is Gene Expression and Development During Growth. It examines the structure and function of chromatin, DNA unwinding proteins, and nonhistone nuclear proteins, then ex- plores transcriptional, translational, and post-translational regulation during the cell cycle and the interrelationship and coordinate regula- tion of cell growth, differentiation, and gene expression. The second section, Growth Activation and Dormancy, focuses upon the events that occur during the transition between active cell growth and proliferative quiescence. The role of DNA strand breaks, protein kinase activity, growth regulatory factors, and the cytoskeleton are examined. Section three discusses The Topology of the Cell Cycle. It reviews genetic approaches for determining the sequence of events and cau- sality relationships that comprise and coordinate the many separate processes involved in cell cycle progression and describes the use of multipara meter flow cytometry to characterize the mammalian cell cy- cle and intracellular metabolic and transitional growth states.

In Molecular Diagnostics for Melanoma: Methods and Protocols, expert researchers and clinicians in the field of melanoma provide updated information on biomarkers and assays for diagnosis, prognosis, and assays predicting response to treatment for routine testing. The focus of the volume is on biomarkers with established clinical validity rather than those on early discovery stage. With additional in-depth discussion of the molecular biology and pathology of melanoma, treatment options in adjuvant and metastatic setting, and implications of biomarker testing for clinical management of melanoma patients. Written in the highly successful Methods in Molecular Biology series format, chapters include extensive introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Comprehensive and practical, Molecular Diagnostics for Melanoma: Methods and Protocols seeks to provide both clinicians and scientists with technical information and extensive background information on the wide ranging approaches available in the field of diagnostics of melanoma.

The first edition of Oncogenes (1989) focused on several of the better known transforming mechanisms and surveyed a spectrum of solid tumors and hematologic malignancies. Several of the nearly 50 known oncogenes most relevant to human disease were examined. In contrast, this volume presents a very different profile and balance of subject material that reflects the rapidly changing field of molecular oncology and its newly emerging concepts. Among the most important discoveries of the past 4 years are the identification of nearly a dozen different tumor suppressor genes and the finding of an entirely new class of cancer-causing gene (bcl-2) that acts by inhibiting cell death rather than stimulating cell proliferation. This edition begins by reviewing selected malignancies in which our earlier search for clinically relevant oncogenes has led to more focused studies on gain-of-function and loss-of-function genetic abnormalities, as well as autocrine and paracrine growth factor loops known to regulate tumor physiology and malignant cell behavior. Curiously, many of these genetic and functional abnormalities are shared by several different tumor types and are not uniformly present in all tumors of the same type. This observation brings up molecular questions about the tissue-specific determinants that underlie individual cancers and also gives added impetus to the suggestion that molecular abnormalities (referred to as tumor markers) be included among the histopathologic features used for clinical diagnosis and manage ment."

This volume provides a thorough overview of the Wilms' Tumour Gene (WT1). The book begins with three review chapters that cover the involvement of WT1 in pediatric cancer, kidney disease, and tissue development and homeostasis. The next few chapters discuss cell marking and lineage tracing, epicardial cell methodology, colony forming assays for bone marrow stem cells, angiogenesis assays and zebrafish tools. The next group of chapters explores the latest tools in genomics, molecular biology, and biochemistry. They discuss dissecting transcription factor function in cell free systems, ChiP seq, proteomics, RNA interactome, and multiphoton imaging of lipids, measuring the binding constants of protein-nucleic acid interactions, and bioinformatics approaches for analyzing Next Generation Sequence data. The final chapter discusses protocols for clinical trials for immune therapy using anti-WT1 peptides. 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. Practical and thorough, The Wilms' Tumour (WT1) Gene: Methods and Protocols is a valuable resource for anyone who is interested in the diverse methodologies used in WT1 research.

This book discusses the aspects of haploidentical transplants and will shed light on the debates and questions on this burgeoning field and timely topic. Donor selection, graft failure, minimal CD34+ cell requirement, and conditioning regimens used for haploidentical transplants will be written by expert authors dealing with this type of transplants. Approximately one third of the books' chapters cover logic and basic aspects; the remaining two thirds of the book discuss clinical aspects, outcomes, and future perspectives, thus providing a comphrensive discussion of the topic. Haploidentical transplantation is extremely timely, rapidly-changing area and increasing its use will decrease the need for time-consuming, expensive, unrelated donor search. Moreover, Haploidentical Stem Cell Transplantation brings a set of clear answers to questions of feasibility, advantages over unrelated transplants, cost effectivity and outcome..

Exciting new developments and discoveries of the last two decades are beginning to shed light on the complex biology of brain tumors and are advancing our understa- ing of the cellular and molecular processes involved in their initiation, progression, and clinical and biological behavior. The disease process in brain tumors is quite complex and the resulting tumors are characterized by a high degree of biological and clinical diversity. Thus, despite the advances of the last two decades, prognosis for patients with malignant brain tumors remains abysmal. Significant progress in the diagnosis, treatment and, ultimately, prevention of these tumors will require both the timely h- nessing of the advances in basic and clinical brain tumor research, and a continuing concerted effort at increasing our understanding of brain tumor biology, in particular, the molecular genetic changes and perturbations of cellular pathways involved in brain oncogenesis and which drive the biological and clinical behavior of the tumors. Brain tumor diagnosis and prognosis, which is still largely based on histopathology and other clinical criteria, will, in the future, acquire a significant molecular component, with the incorporation of knowledge of genes that are mutated, over-expressed, deleted, silenced, or functionally altered in the tumors. Treatment strategies for brain tumors, rather than being empirical, will be rationally developed based on an understanding of the cellular and molecular mechanisms and targets that have been activated, suppressed, or otherwise altered.

In recent years there have been various discoveries connecting inflammation and lung cancer and clearly there is growing interest in this area of cancer research. The link between unresolved inflammation and cancer has been well established with estimates that 15% of cancer deaths are inflammation-related. Evidence for this link includes the following: a) some inflammatory diseases are associated with increased risk of cancer development; b) inflammatory mediators are present surrounding and within most tumors; c) overexpression of inflammatory cytokines increases cancer development and progression in murine studies; d) inhibition of inflammatory mediators decreases cancer development and progression; and e) the use of non-steroidal anti-inflammatory drugs (NSAIDs) has been found to decrease cancer incidence and delay progression. The volume will present aspects of the inflammatory tumor microenvironment (TME), its many roles in tumor progression and metastasis, including creation of a hypoxic environment, increased angiogenesis and invasion, changes in expression of micro-RNAs (miRNAs) and an increase in a stem cell phenotype. The book will also cover the mechanisms of inflammatory mediators. Chronic overexpression of inflammatory mediators in the TME, as seen in smokers and patients with non-small cell lung cancer (NSCLC), can also lead to increased tumor initiation, progression, invasion and metastasis. The volume will provide a comprehensive perspective of the latest findings and summaries of progress made regarding inflammation and its connection to lung cancer.

In the United States alone, the incidence of new cases of thoracic neoplasms is over 180,000. Each year, over 170,000 individuals are expected to die of their cancer. Lung cancer is the most common of the thoracic neoplasms. It is the leading cause of cancer death in both men and women, accounting for 28% of all cancer deaths in the United States. Thoracic Oncology provides an up-to-date and concise review of the various thoracic neoplasms and offers a better understanding of the biology, natural history, diagnosis and treatment of these malignancies. This book will be of particular interest to clinicians interested in thoracic neoplasms, to better understand and treat them.

In Breast Cancer Chemosensitivity, a group of world leading experts review critical aspects of resistance to systemic therapy in breast cancer patients. Beginning with a clinical overview of the problem, the book then focuses on the latest findings of molecular mechanisms of drug resistance. Coverage provides an example of using novel approaches for chemosensitization of breast cancer cells that gives readers an idea about the future direction in breast cancer treatment. It allows those who are interested in breast cancer therapy to get a jump-start on critical issues in breast cancer therapeutic resistance.

This series of books, devoted to aspects of blood cell biochemistry, development, immu nology, and ultrastructure, has evolved and separated from the long-established Plenum series Subcellular Biochemistry. It is the intention of these volumes to draw together related areas of investigation and to provide, in the fullness of time, complete coverage of this rapidly advancing important biomedical discipline. Both fundamental and medically applied topics, dealing with normal and pathological cells, will be included. This, the first volume of the series, contains a diverse collection of chapters, all of which relate to erythroid cells. The range of material included is extremely broad and the authors have used contrasting technical approaches, both within their personal experimen tal studies and within their manuscripts. This has led to the production of a very interest ing compilation, which does, nevertheless, possess a strong overall thematic unity. As with all edited volumes, some topics of importance and interest are not included. This may be because of oversight on my part, as editor, or because the authors originally selected failed to submit their manuscript by the agreed-upon submission date. For these omissions I take full responsibility and trust that at least some of the topics omitted, for instance membrane cation transport systems, will be covered within a future volume of the series. This book commences with two chapters of a developmental nature."

Focused on the discovery of precise molecular targets for the development of the cancer preventive agents, "Cancer Prevention: Dietary Factors and Pharmacology" provides researchers and non-researchers with practical methodologies for developing and validating small molecule and phytochemical-derived drug discovery and mechanisms by which these compounds can modulate distinct target proteins involved in oncogenic signaling. While this volume is primarily focused toward cancer prevention research, the range of techniques demonstrated in the book also provides an introduction of cancer prevention research methods to researchers outside the field. Chapters deal with a critical discussion of both laboratory and clinical topics, with each chapter containing both a discursive section along with a detailed methods section. As part of the "Methods in Pharmacology and Toxicology" series, this meticulous volume includes the kind of key implementation advice that seeks to ensure successful results in the lab.

Practical and authoritative, "Cancer Prevention: Dietary Factors and Pharmacology" aims to guide research toward identifying molecular targets and conducting human studies with phytochemicals which would, ideally, provide an enhanced approach to the goal of personalized cancer prevention.