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Although mechanisms involved in the spread of cancer have been the subject of a major research endeavor over the past decade, metastatic tumors still account for significant clinical morbidity and the failure of cancer treatment. Not only are the vascular pathways the most common route for the dissemination of cancer cells, but interactions between the cells and the circulation act as important rate-regulators for the metastatic process.This authoritative, multi-authored volume addresses the importance of microcirculation in cancer metastasis. The book begins with up-to-date reviews on the biology of endothelial cells and the structure and physiology of the normal and tumor microcirculations, and then emphasizes interactions between components of the microcirculation and cancer cells. Metastasis is discussed through chapters exploring the entry of cancer cells into the circulation, the biophysics and morphology of cancer cell traffic and arrest, interactions with host cells and the basement membranes, and angiogenesis. This fascinating book will interest oncologists, pathologists, and students of metastasis or the microcirculation.

This volume provides the latest research on circulating tumor cells aimed for cancer researchers, scientists, and molecular oncologists. It presents the basic concepts behind circulating tumor cells (CTCs), metastatic biology, and potential applications as to how CTCs can be used in diagnostic biomarkers.CTCs are cells that have detached from the primary tumor and circulate in the bloodstream. Such cells may become'seeds'for the growth of additional tumors. The field of analysis surrounding cancer metastasis has been steadily growing, and CTCs provide effective biomarkers that can be examined in peripheral blood through a minimally invasive “liquid biopsy” procedure. CTCs offer several exciting applications, not only as markers of disease progression but also as biomarkers of monitoring response to therapy and companion diagnostics for novel anticancer drug development. In recent years there has been rapid growth and worldwide developments on CTCs, which span both the basic sciences and biomedical engineering fields.

This monograph summarizes state of the art knowledge regarding peritoneal surface malignancies, with in-depth description of treatment options and the results achieved to date. It explores the most challenging problems on the basis of the authors'very extensive clinical experience and examines the most relevant clinical trials. A comprehensive summary is provided of all phase 2 studies (the only available completed studies) and of ongoing and future phase 3 studies. Particular attention is paid to the results of integrated treatment comprising cytoreduction (peritonectomy) and hyperthermic intraperitoneal chemotherapy (HIPEC). Helpful background information is also included on the definition and clinical assessment of each clinical form. The book, drawing on data from the entire Italian experience as well as world literature, will be an outstanding benchmark for health professionals and researchers.

Breast Cancer provides an in-depth understanding of the biology of breast cancer, the natural history of the disease, the use of molecular markers, the interpretation of clinical trial data, and the integration of multiple therapeutic modalities. The single most important fact about breast cancer is the great variation in its natural history and its responsiveness to therapy from one patient to another. The clinician must integrate an assessment of the patient's likely course based on clinical and pathological staging and laboratory studies with objective evidence on the benefits of therapy. The primary aim of this book is to provide the clinician with the tools to do just that. Outcomes of clinical trials and details about commonly used drug regimens, drug dosage, and the expected side effects are summarized in generous tables and figures. Medical terminology has been defined and descriptions of the evolution in our thinking and understanding of the disease are often given to provide perspective in the interpretation of evidence from current studies for busy clinicians and trainees alike.

The last 15 years have brought an understanding of growth and differentiation at the molecular level, expanding our knowledge of the origin and progression of cancer. Early breakthroughs defining growth control pathways came via studies of oncogenes, mutated signaling molecules that have lost the capacity to tum off their proliferative signal. Oncogenes with diverse growth-promoting activities have been discovered, covering the gamut from cell surface to nuclear signaling. Sequencing of these oncogenes revealed that they were mutated forms of captured cellular genes and displayed tyrosine kinase activity. The epidermal growth factor (EGF) receptor was the first of 40-50 transmembrane tyrosine kinase receptors to be cloned and sequenced. Beyond cell proliferation, activation of EGF receptor by its specific ligands controls important physiological processes, such as cell differentiation, apoptosis, cell migration, and cell shape. Activation of autocrine growth loops, consisting in solid human tumors of upregulated expression of EGFR together with increased production of ligands suggested its crucial role in autonomous tumor growth.

A focused, accessible introduction to this key aspect of cancer biology. It covers the individual cell signalling pathways that are known to be involved in cancer development, and, most important, includes the cross- interactions between the pathways together with the current therapeutic approaches. This is a ‘must-have'for advanced undergraduate and postgraduate students studying and researching within the field of cancer biology.

This volume emphasizes metastasis/dissemination as im­ nective tissues, muscle, tumours of neuronal origins and portant processes in cancer growth and progression. teratomas. Previous volumes in this series have emphasized aspects of The broad array of neoplastic diseases, multiple target cancer progression, tumor invasion and tumor metastasis sites, and patterns of metastasis and dissemination underlie and the importance of these processes to the pathophysiol­ the importance of achieving crucial insights into particular ogy and morbidity of malignant disease. This volume builds neoplasms. An understanding of metastasis and dissemina­ on these earlier themes and emphasizes metastasis/disse­ tion in man remains an essential objective for the design of mination in man. Following a review of general patterns of new diagnostic and therapeutic strategies for the therapy of metastatic spread in man, metastasis to, or progression of established metastatic disease and spread accompanying neoplasms in several organ systems are highlighted, includ­ site-specific tumor progression. ing: the central nervous system, esophageal cancer, the lung, the large intestine, the liver, bone, epithelial neoplasms, Series Editor Volume Editor endocrine cells, pigmented tissues, supporting tissues, con- Hans E. Kaiser Elizier L. Gorelik VII ACKNOWLEDGEMENT Inspiration and encouragement for this wide ranging project on cancer distribution and dissemination from a comparative biological and clinical point of view, was given by my late friend E. H. Krokowski.

It is widely appreciated that the pathophysiology of advanced brain cancer is intimately related to the extent of tumor invasiveness. A prerequisite for comprehensively understanding neuro-oncology is therefore the elucidation of the biochemical and molecular properties of tumor cells that contribute to their invasiveness. An understanding of tumor invasion for central nervous system tumors is crucial since malignant brain tumors are very highly invasive and extensively destroy adjacent neural brain tissue. Moreover, they are angiogenesis-dependent and lead to the death of patients by expanding within the limited space of the cranium. As more specific insights are gained towards a full understanding of the complex process of tumor invasiveness of brain tumor cells, it should be possible to design strategies for the early diagnosis and treatment of invasive, advanced brain tumors. There is therefore an urgent need to better understand the cellular properties of brain tumor cells responsible for invasiveness. This special issue of the JOURNAL OF NEURO-ONCOLOGY provides a state-of-the-art review of the general understanding of the process of tumor invasion. In addition, the articles emphasize specific aspects of aggressive brain cancers which are particularly important for deriving new insights for therapeutic approaches for advanced brain cancer that will target tumor invasiveness. The ideas discussed will stimulate further studies directed towards the translation of these important invasion-related studies to clinical approaches for the effective treatment of brain cancer.

This book is directed primarily to advanced graduate and medical students, postdoctoral trainees, and established investigators having basic research interests in neoplasia. Its content is based in part on the lecture outlines and selected histopathology laboratory components of an advanced course entitled The Pathobiology of Experimental Animal and Human Neoplasia, developed by me for the Experimental Pathology Curriculum of the Department of Pathology at the Medical College of Virginia. In this regard, an effort has been made to integrate pathology with carcinogenesis, genetics, biochemistry, and cellular and molecular biology in order to present a comprehensive and current view of the neoplastic process. For focus, emphasis is mainly being placed on the neoplastic cells themselves, and not on associated host-mediated responses. It ishoped that this book will accomplish its purpose of providing students and researchers who already possess strong but diverse basic science backgrounds with unifying concepts in tumor pathobiology, so as to stimulate new research aimed at furthering our understanding of neoplastic disease. I wish to express my appreciation and heartfelt thanks to the authors, whose individual ranges of expertise and research experience clearly bring to their respective chapters unique perspectives that easily transcend any redundancy that may be present. In addition, I am grateful to Drs. George Vennart, Saul Kay, and Fred Meier, and to Ms. Connie Wilkerson of the Department of Pathology at MCV, for their helpful comments and their review of some of the material.

The presence of multiple cancers in one patient has excited the interest of many investigators, and considerable literature has accumulated on this subject. The scientific concepts and clinical importance of field cancerization are the subject matter of this book. This book is a compendium of importance to oncologists and cancer researchers and caregivers. Existent knowledge on cancer biology and therapy has been vastly expanded by this concept of cancer evolution. Expanding “super-competitors”, multistep carcinogenesis, and stem cell theories are some novel mechanistic models of carcinogenesis discussed in this book. Extensively covered in this book as well, are the cellular and molecular changes representative of field cancerization in several cancers, including hematologic and pediatric cancers.

In human solid tumors, nodal status is the most important prognostic indicator for patient outcome. Recent developments in the sentinel lymph node concept have resulted in new procedures to define the first draining node as the primary gateway through which the cancer will spread. In From Local Invasion to Metastatic Cancer: Involvement of Distant Sites Through the Lymphovascular System, a panel of international authorities takes an in-depth look at the role of the lymphovascular system in the spread of cancer. The authors summarize the findings of the Second International Symposium on Cancer Metastasis: Basis for Rational Therapy summit. Specifically, the book presents important developments in the biology and clinical understanding of cancer metastasis, describes the relationship between tumor microenvironment and proliferation, and defines the process of lymphangiogenesis and angiogenesis with special reference to cancer metastasis. From Local Invasion to Metastatic Cancer: Involvement of Distant Sites Through the Lymphovascular System provides oncologists, radiologists, and cancer researchers the necessary information to study and develop new strategies to curb the process of metastasis.

The processes of tumor metastasis, apoptosis and anti-tumor immune response are among the most complex yet rapidly advancing fields in the area of cancer research. This monograph presents a comprehensive coverage of the recent advances in the various key concepts in these fundamental aspects of human cancer. It would be of particular interest to members of the cancer research community, especially those who are actively involved in the study of basic and translational aspects of human cancer. Specifically, this volume includes authentic subject reviews by leading experts on the following aspects: Control of tumor cell motility Role of tumor-cell adhesion and migration in organ-selective metastasis-formation Tumor heterogeneity in relation to invasion and metastasis and its clinical implications Tumor angiogenesis, angioprevention, anti-angiogenic therapies and response Role of apoptosis in the development, progression and therapy of cancer Role of macrophages in tumor development and metastasis Pathways of macrophage-mediated tumor progression Abnormal variation of immune response against cancer Immunological aspects of Marek's disease virus (MDV)-induced lymphoma progression A biodynamical model of human T-cell proliferative disorders Current methodologies for characterization of tumor directed immune response.

Invasive Bladder Cancer draws on the expertise of an international community of experts in the area. It offers an updated, simple overview bridging the information coming from basic research to clinical practice, facilitated by most chapters having both a basic researcher and a clinician writing together. The book will be of particular interest to office urologists, and oncologists with a specialist interest in urology.

Description based on print version record.

Provides an overview of cell invasion. Topics include information on the cellular matrix, cell surface integrins, matrix metalloproteinases and proteinases, and the interplay between protein families.

Although distant metastases are the most dreaded situation in the evolution of cancer of every organ, the medical literature has surprisingly given little attention to the anatomical relationship between the primary tumor and metastasic sites. Only risk factors, treatment possibilities, and survival results are extensively examined. Stimulated by the occurrence in his practice of some puzzling and unexpected metastases, the author reviewed more than 12,000 references. He looked for anatomical relationships highlighting the relation between the location of the primary tumors and the particular patterns of metastasis observed. It would seem that the `pathways and flows'are apparently a more decisive factor in the implantation of the metastases than the `seed and soil'properties of the cancer cells and the metastatic site. Aided by his colleague Dr. T. Geukens, M.D., the author includes original anatomical drawings, illustrating the sometimes unexpected pathways the cancer cells follow in order to reach the organs where they will become lodged and give rise to metastatic tumors. The subject has apparently not been exhausted in the literature and several ideas are given for further research.

Calcium signalling occupies a preeminent position in the signal transduction system of the cell by virtue of its participation in a wide range of physiological functions together with the biological events associated with genetic expression, cell proliferation and apoptosis, as well as cell differentiation and morphogenesis. It is an important feat

'Symposium on the Tumour Microenvironment: Causes and Consequences of Hypoxia and Acidity, held at the Novartis Foundattion, London, October 10-12, 2000'--Contents p.

Written by internationally recognized experts, The Genetics of Cancer provides up-to-date information and insight into the genetic basis of cancer and the mechanisms involved in cancer invasion and its secondary spread. This volume presents the deregulation of the cell cycle in tumor development and integrates the function of tumor suppressor genes, oncogenes, and metastasis-associated genes in the pathogenesis and progression of cancer. The Genetics of Cancer will be useful to all graduate students, clinicians, and researchers working in the fields of cancer biology, genetics, and molecular biology. - Clonal evolution of the metastasis phenotype - Cell Cycle regulation - Apoptosis in tumour growth and metastasis - Angiogenesis in cancer - Cell surface glycoproteins and their receptors - Proteinases and their inhibitors in cancer invasion - Oncogenes and cancer metastasis - Developmental genes - Tumour suppressor genes - Metastasis suppressor genes - Dominant metastasis-associated genes