Contemporary Biomedicine – serie

The earliest and still most widely used method of identification of cancer tissue or cells is the structural resemblance of cancer tissue to fetal or immature tissue.

The ability to diagnose cancer by simple measurement of a serum or tissue' 'marker" has been a goal of medical science for many years. There is ample evidence that tumor cells are different from normal cells and pro­ duce substances that can be detected by currently available immuno­ chemical or biochemical methods. These "cancer markers" may be se­ creted proteins, enzymes, hormones, fetal serum components, monoclonal immunoglobulins, cell surface components, or cytoplasmic constituents. The purpose of this book is to present the current status of our knowledge of such cancer markers. The first tumor marker identified by laboratory means was Bence­ Jones protein. In a series of lectures delivered to the Royal College of Phy­ sicians in London in 1846, Dr. H. Bence Jones described studies on a urine sample sent to him with the following note: "Dear Dr. Jones-The tube contains urine of very high specific gravity. When boiled it becomes slightly opaque . . . . etc. " Dr. Jones found that heating of the urine after addition of nitric acid resulted in formation of a heavy precipitate; acid ad­ dition may have been required to bring the urine to pH 4-6 at which Bence Jones proteins are more likely to precipitate when heated. This urinary pre­ cipitate was associated with a bone disease termed "mollities ossium. " [H. Bence Jones, Papers on Chemical Pathology, Lecture III. Lancet 2, 269-274 (1847)].

Human teratocarcinoma has long held a fascination to the pathologist be- cause of the diversity of the seemingly benign differentiated tissues asso- ciated with the tumor. An understanding of this diversity came with the demonstration of the pluripotent nature of the embryonal carcinoma cell, the stem cell of the tumor, in experimental animals. Single cell clones of murine embryonal carcinomas were derived and the resultant cell lines injected into immunosuppressed hosts, where the embryonal carcinoma stem cell itself gave rise to the wealth of differentiated tissues seen in teratocarcinomas. It was also shown that teratocarcinomas could be pro- duced experimentally by transplantation of staged early mouse embryo to extrauterine sites; subsequent experiments suggested that the embryonal carcinoma stem cell was, in fact, comparable to a normal cell of the em- bryonic ectoderm. Many elegant experiments have since been built on this early work; murine embryonal carcinoma cells are providing the ex- perimental material for a first biochemical evaluation of the earliest dif- ferentiation events in mammalian embryogenesis.In this volume, we relate the beginnings of experimental research on human teratoma. The human embryonal carcinoma cells have been char- acterized and established in vitro, providing an experimental model to study the unique biology of these cells. Monoclonal antibodies, estab- lished from work with these in vitro cultures, provide cell surface probes that define populations of embryonal cells and their derivatives in tumor sections.

Cancer has become the most critical health problem in the United States. It is expected that 25% of the people will develop this dread disease, and many of these will die from the malady. The causes of cancer are varied, but the best estimate available is that 70--90% arise from environmental factors. These statistics have triggered widespread governmental action along two lines: (l) An effort to identify those chemicals and conditions that give rise to malignant processes has been mounted by the Carcino­ genesis Testing Program, the National Cancer Program, and subse­ quently, the National Toxicology Program. (2) Regulatory laws have been enacted that are administered by agencies such as TSCA, FIFRA, EPA, FDA, OSHA, and so on, whose mission is to minimize public ex­ posure to carcinogens. Since direct verification that specific chemicals induce cancer in hu­ of unanticipated expo­ mans is necessarily limited to known incidences sure and is therefore rare, most chemicals are identified as carcinogens only by laboratory experiments. At present, the only accepted procedure is long-term animal bioassay, and not only are these studies expensive and time-consuming, but current worldwide resources permit the evalua­ tion of only 300-400 chemicals per year, a miniscule amount compared to what is available in the commercial world: 30,000 existing chemicals, with approximately 700 new such materials being introduced every year.

In organizing the present volume, we had two intentions. The first was to present the best current understanding of the mechanisms of calcium mobilization during excitation­ contraction coupling of smooth muscle at a level suited to the needs of professionals interested in smooth muscle pharmacology and pathophysiology, while remaining appreciable by graduate and medical students. The second intention was to provide in­ sight into present-day controversies, as well as the latest ad­ vances achieved by researchers in this field. Thus, we have thor­ oughly discussed both the techniques and the concepts derived from their application. An attempt has also been made here to answer a number of profoundly important questions: What are the mechanisms and agents responsible for the control of contractility? What are the accompanying changes in the state of intracellular calcium ions and the mechanisms responsible for them? How does the regula­ tion of contractility occur directly at the level of the actomyosin activity? What role do gap junctions play in cell-to-cell coupling? What are the roles of cholinergic, adrenergic, peptidergic, and nonadrenergic noncholinergic interactions in calcium mobiliza­ tion in smooth muscle? What changes occur in hypertension? The impact of these recent techniques on future research is also reflected upon.

This represents the third volume in a series on cancer markers pub- lished by the Humana Press. The first volume, published in 1980, stressed the relationship of development and cancer as reflected in the production of markers by cancer that are also produced by normal cells during fetal development. The concept that cancer represents a problem of differentiation was introduced by Barry Pierce in describing differenti- ation of teratocarcinomas. Highlighted were lymphocyte markers, alphafetoprotein, carcinoembryonic antigen, ectopic hormones, enzymes and isozymes, pregnancy proteins, and fibronectin. The second volume, published in 1982 and coedited with Britta Wahren, focused on the diagnostic use of oncological markers in human cancers, which were systematically treated on an organ by organ basis. At that time, the application of monoclonal antibodies to the identification of cancer markers was still in a very preliminary stage. A general introduc- tion to monoclonal antibodies to human tumor antigens was given there by William Raschke, and other authors included coverage of those mark- ers then detectable by monoclonal antibodies in their chapters.

Laymen often consider modern laboratory research to be based on an endless array of sophisticated technologies whose complex capabilities are as important to the outcome of any project as the inventiveness and creativity of the scientists who employ them. Scientists at times may share this point of view until they are con­ fronted by unexpected findings that demand new approaches, and they discover that yesterday's "sophisticated tools" are today's "blunt instruments." This experience provides a more sobering view of the current state of our scientific methods. It also serves as an impetus for the further development of technology that prepares us for the next stage of advance. Immunologists were confronted by such a technological crises in the late 1970s when they finally were forced to admit that poly­ clonal antibodies, although quite sensitive reagents, were not spe­ cific enough to answer many of the questions then confronting virologists and tumor biologists. The answer to the need for specific­ ity came with the development of monoclonal antibody technology. In the last ten years there have been considerable advances in monoclonal antibody techniques. Today these reagents are much more versatile than they were initially and can be applied to a broad range of problems. Still, most workers who are using these anti­ bodies are convinced that their potential is far from exhausted, and that at least in some fields we are currently in the early stages of learning how to use them properly.

Regulation of malignant cell growth by the immune system has been extensively studied by cancer researchers hoping to develop immuno­ therapeutic approaches to cancer management. For years these studies revolved around the recognition and destruction of tumors by cytotox. ic immune effector cells. Recently, however, attention has focused on the leukolysins, which are the soluble cytotoxic molecules secreted by activated leukocytes, because of their anticancer activities. The purpose of this book is to give an overview of the ieukolysins, with emphasis on their ability to regulate malignant cell growth. Because this is such a new field in cancer research, there remains some confusion regarding the tenninology of. and biological activity ascribed to, the different leukolysins. Therefore, we sought to present a comprehensive review of the leukolysins currently under intensive study and to compare and contrast their biological activities in an attempt to clarify the nature of these diverse biological species. This book is intended for both immunologists conducting basic research and clinical oncologists, since it reviews not only the clinical applications of the leukolysins, but presents a current update on those leukolysins that are in early developmental stages of research and could enter into clinical trials in a few years. The introduction gives an overview of the status of research on the leukolysins. In the first section, the biological activities and biochemical characteristics of the leukolysins are presented. The lymphokines.

In 1868, Ernst Neumann recognized that blood cells re­ quire continuous replenishment during postnata1life. Before him, the assumption was that cells of the blood, like nerves once formed in the embryo, remain in the body throughout life. Neumann also recognized that this process occurred within the bone marrow, because this tissue provided a fa­ vorable environment for proliferation and differentiation of blood cell precursors. Vera Danchakoff, the Russian embryologist working in the US, in 1916 made an analogy to the soil and the seed. Bone marrow forms the soil, providing a favorable environment for the growth of seed, the hemopoietic stem cell, and other progenitor cells. Imagine in the remote past a heap of similar tree seeds. These seeds develop in our moderate climate into a tall and many branched tree. Suppose the wind bears a part of the seeds away and brings them to a land possessing different environmental conditions, we will say the arc­ tic lands. There the seeds may develop but they may pro­ duce trees no higher than our moss.

"After being frequently urged to write upon this subject, and as often declining to do it, from apprehension of my own inability, I am at length compelled to take up the pen, however unqualified I may still feel myself for the task. " William Withering, M. D. ' I have yet to find a description or a quote that better summanzes my initial ambivalence towards embarking on such an endeavor as partici­ pating in putting together this monograph. The impetus for The Red-Cell has been a simple, genuine Membrane: A Model for Solute Transport desire to bring together an authoritative account of the' 'state of the art and knowledge" in the red-ceIl-membrane transport field. In particular, it seems important to emphasize the pivotal role the red cell has played for several decades in the discovery and the elucidation of mechanisms of plasma-membrane transport processes. It is only with such knowledge that we can hope to push ahead and make progress in this exciting, multifaceted area. Eventually, one hopes to not only further our knowledge of red cells, but apply the newly gained insights to any other of the plasma membrane. cell with the common denominator In this compendium of reviews, the reader will find that the term model will take on a variety of gists and meanings. In some chapters, the red cell has been chosen as a model membrane solely on the basis of its preeminent design and simplicity.

This latest volume edited by Stewart Sell provides up-to-the-minute information on the clinical use of cancer markers - focusing on those detected in the serum - for the diagnosis of cancer, as well as for monitoring various aspects of patients' progress and prognosis. These markers can be detected by monoclonal antibodies and molecular probes. Serological Cancer Markers takes into account the rapid growth in applications of these cancer marker assays that have recently been developed. Experts in cancer research have contributed chapters that cover a wide range of tests and other information, including: carbohydrate epitopes mucin epitopes cytoplasmic proteins alkaline phosphatases sex-linked hormones alphafetoprotein myeloma paraprotein reagents for measuring cancer markers detection of hidden lesions by specific direction of radioisotopes marketability of new cancer products multiple testing with cancer markers future trends. Stewart Sell's new Serological Cancer Markers is an indispensable, state-of-the-art resource for everyone involved in cancer research, clinical oncology, and related fields.

In Cellular Cancer Markers leading pathologists and physicians review today's most promising cellular cancer markers, an important emerging class of prognostic markers that can be used in the clinical evaluation of cancer patients. The markers reviewed have been chosen because they are biologically relevant to the growth of cells and possess an accurate and reproducible assay for detection. They also are predictors of tumor behavior, are useful in making clinical decisions, and are cost effective. Cellular Cancer Markers provides a status report for markers of tumor cell activation, proliferation, and longevity that makes possible an informed judgment regarding the value of many newly proposed tumor markers. It also offers insight into the latest approaches to diagnosing cancer and an appreciation of how these marker-based tests can clarify the prognosis of cancer.

An unprecedented compilation of state-of-the-art advances in clinical research on diabetes and obesity by premier clinical scientists around the world. This volume critically reviews the limitations and strengths of today's major techniques in clinical diabetes research, and then reviews how those methods have been used to carry out cutting-edge studies of carbohydrate, lipid, and protein metabolism in the disease.

Seventeen cutting-edge chapters review both basic research and clinical applications of chromosomal markers of cancer. The new markers offer great promise, not only for their clinical utility in diagnosis, prognosis, and disease monitoring, but also for their contributions to a better understanding of the mechanisms of tumor development and progression. The chapters - all written by leading authorities - skillfully reveal fresh insights into the translational role of cytogenetics in identifying the cellular and molecular changes that occur in cancer. Coverage is devoted to many tissue systems - colon, breast, prostate, lung, skin, brain, and kidney - where the diagnostic and prognostic utility of chromosome markers is clearly demonstrated. A seminal book certain to become the front-line reference and authoritative resource needed by all scientists and clinicians engaged in cancer research, diagnosis, and management.

A unique, integrated collection of original contributions on the molecular biology, physiology, and pathology of endothelin. Leading academic, clinical, and industrial researchers summarize the dramatic recent progress in endothelin research and indicate the optimal direction of future studies. The contributors produce a critical evaluation of endothelin chemistry and pharmacology, its mechanism of action, and its physiological functions. The book is certain to become the new standard reference source for both basic scientists and informed clinicians who want a clear idea of the roles endothelin may play in cardiovascular physiology and pathology.

An unprecedented compilation of state-of-the-art advances in clinical research by premier clinical scientists around the world. This volume discusses the methods of clinical research and the interpretation of their results in studies of normal individuals, obese subjects, and patients with diabetes mellitus. Along the way, the authoritative contributors writing here illuminate how changes in the hormone action and substrate metabolism of healthy humans may lead to obesity and noninsulin-dependent diabetes mellitus.

Human teratocarcinoma has long held a fascination to the pathologist be- cause of the diversity of the seemingly benign differentiated tissues asso- ciated with the tumor. An understanding of this diversity came with the demonstration of the pluripotent nature of the embryonal carcinoma cell, the stem cell of the tumor, in experimental animals. Single cell clones of murine embryonal carcinomas were derived and the resultant cell lines injected into immunosuppressed hosts, where the embryonal carcinoma stem cell itself gave rise to the wealth of differentiated tissues seen in teratocarcinomas. It was also shown that teratocarcinomas could be pro- duced experimentally by transplantation of staged early mouse embryo to extrauterine sites; subsequent experiments suggested that the embryonal carcinoma stem cell was, in fact, comparable to a normal cell of the em- bryonic ectoderm. Many elegant experiments have since been built on this early work; murine embryonal carcinoma cells are providing the ex- perimental material for a first biochemical evaluation of the earliest dif- ferentiation events in mammalian embryogenesis.In this volume, we relate the beginnings of experimental research on human teratoma. The human embryonal carcinoma cells have been char- acterized and established in vitro, providing an experimental model to study the unique biology of these cells. Monoclonal antibodies, estab- lished from work with these in vitro cultures, provide cell surface probes that define populations of embryonal cells and their derivatives in tumor sections.

The ability to diagnose cancer by simple measurement of a serum or tissue' 'marker" has been a goal of medical science for many years. There is ample evidence that tumor cells are different from normal cells and pro­ duce substances that can be detected by currently available immuno­ chemical or biochemical methods. These "cancer markers" may be se­ creted proteins, enzymes, hormones, fetal serum components, monoclonal immunoglobulins, cell surface components, or cytoplasmic constituents. The purpose of this book is to present the current status of our knowledge of such cancer markers. The first tumor marker identified by laboratory means was Bence­ Jones protein. In a series of lectures delivered to the Royal College of Phy­ sicians in London in 1846, Dr. H. Bence Jones described studies on a urine sample sent to him with the following note: "Dear Dr. Jones-The tube contains urine of very high specific gravity. When boiled it becomes slightly opaque . . . . etc. " Dr. Jones found that heating of the urine after addition of nitric acid resulted in formation of a heavy precipitate; acid ad­ dition may have been required to bring the urine to pH 4-6 at which Bence Jones proteins are more likely to precipitate when heated. This urinary pre­ cipitate was associated with a bone disease termed "mollities ossium. " [H. Bence Jones, Papers on Chemical Pathology, Lecture III. Lancet 2, 269-274 (1847)].

Developmental cancer products (oncodevelopmental markers, ODM) not only serve as diagnostic and prognostic indicators but also may be used to study the nature of the carcinogenic process and the biology of tumors. For many years oncologists have searched for markers of cancer cells that would permit unequivocal recognition of cancer in contrast to noncancerous tissue. The earliest and still most widely used method of identification of cancer tissue or cells is the structural resemblance of cancer tissue to fetal or immature tissue. Pathologists not only recognize cancer by its morphologic similarity to fetal tissues, but also in many instances can relate the behavior of a given tumor to the degree of tissue differentiation. Thus, poorly differentiated tumors that resemble fetal tissue generally grow more rapidly and metastasize earlier than do well-differentiated tumors that more closely resemble adult tissue. In recent years the commonality of fetal and cancer tissue has been extended to products of tumor cells that, can be analyzed by biochemical, immunological, or physiological techniques. Increas­ ingly, products of cancer cells similar to fetal products are being identified and studied. These products range from cell-surface markers (fetal or differentiation antigens), placental proteins, hormones, and isoenzymes to a multitude of products, such as carcinoembryonic antigen (CEA), alphafetoprotein (AFP), lymphocyte markers, and nucleic acids, such as tRNA, that are produced in small amounts by v vi PREFACE continually differentiating cells in the adult but in much greater amounts by tumors.

The purpose of this book-the fourth volume of a series on Can­ cer Markers-is intended to provide an updated "status report" on today's use of cancer markers in the diagnosis and monitoring of can­ cer, with an emphasis on cancer markers detected in the serum. It has been 7 years since the publication of the last volume in this series. The 1980, 1982, and 1985 volumes covered the development of cancer markers, not only in their roles of unraveling the basic biology of can­ cer, but also as increasingly important players in the management of patients with cancer. During the last 7 years we have seen the applica­ tion of a number of markers identified by monoclonal antibodies, as well as the beginnings of the use of genetic markers defined by mo­ lecular probes. Measurements of oncogenes in tissues or cells prom­ ise many applications for the future, but as yet, these genes have not shown to be useful as serum markers of cancer. The commercial interest in serum markers for cancer, particu­ larly for the diagnosis and monitoring of tumor patients, is indicated in Chapter 24 by Owen, where the total worldwide market for cancer markers is projected to increase from $148 million in 1988 to $232 million in 1993. The degree of research interest in cancer markers is reflected in the fact that in 1988 a separate category for tumor mark­ ers was added to Index Medicus.

Seventeen cutting-edge chapters review both basic research and clinical applications of chromosomal markers of cancer. The new markers offer great promise, not only for their clinical utility in diagnosis, prognosis, and disease monitoring, but also for their contributions to a better understanding of the mechanisms of tumor development and progression. The chapters-all written by leading authorities-skillfully reveal fresh insights into the translational role of cytogenetics in identifying the cellular and molecular changes that occur in cancer. Coverage is devoted to many tissue systems-colon, breast, prostate, lung, skin, brain, and kidney-where the diagnostic and prognostic utility of chromosome markers is clearly demonstrated. A seminal book certain to become the front-line reference and authoritative resource needed by all scientists and clinicians engaged in cancer research, diagnosis, and management.

In 1868, Ernst Neumann recognized that blood cells re­ quire continuous replenishment during postnata1life. Before him, the assumption was that cells of the blood, like nerves once formed in the embryo, remain in the body throughout life. Neumann also recognized that this process occurred within the bone marrow, because this tissue provided a fa­ vorable environment for proliferation and differentiation of blood cell precursors. Vera Danchakoff, the Russian embryologist working in the US, in 1916 made an analogy to the soil and the seed. Bone marrow forms the soil, providing a favorable environment for the growth of seed, the hemopoietic stem cell, and other progenitor cells. Imagine in the remote past a heap of similar tree seeds. These seeds develop in our moderate climate into a tall and many branched tree. Suppose the wind bears a part of the seeds away and brings them to a land possessing different environmental conditions, we will say the arc­ tic lands. There the seeds may develop but they may pro­ duce trees no higher than our moss.

"After being frequently urged to write upon this subject, and as often declining to do it, from apprehension of my own inability, I am at length compelled to take up the pen, however unqualified I may still feel myself for the task. " William Withering, M. D. ' I have yet to find a description or a quote that better summanzes my initial ambivalence towards embarking on such an endeavor as partici­ pating in putting together this monograph. The impetus for The Red-Cell has been a simple, genuine Membrane: A Model for Solute Transport desire to bring together an authoritative account of the' 'state of the art and knowledge" in the red-ceIl-membrane transport field. In particular, it seems important to emphasize the pivotal role the red cell has played for several decades in the discovery and the elucidation of mechanisms of plasma-membrane transport processes. It is only with such knowledge that we can hope to push ahead and make progress in this exciting, multifaceted area. Eventually, one hopes to not only further our knowledge of red cells, but apply the newly gained insights to any other of the plasma membrane. cell with the common denominator In this compendium of reviews, the reader will find that the term model will take on a variety of gists and meanings. In some chapters, the red cell has been chosen as a model membrane solely on the basis of its preeminent design and simplicity.

Regulation of malignant cell growth by the immune system has been extensively studied by cancer researchers hoping to develop immuno­ therapeutic approaches to cancer management. For years these studies revolved around the recognition and destruction of tumors by cytotox. ic immune effector cells. Recently, however, attention has focused on the leukolysins, which are the soluble cytotoxic molecules secreted by activated leukocytes, because of their anticancer activities. The purpose of this book is to give an overview of the ieukolysins, with emphasis on their ability to regulate malignant cell growth. Because this is such a new field in cancer research, there remains some confusion regarding the tenninology of. and biological activity ascribed to, the different leukolysins. Therefore, we sought to present a comprehensive review of the leukolysins currently under intensive study and to compare and contrast their biological activities in an attempt to clarify the nature of these diverse biological species. This book is intended for both immunologists conducting basic research and clinical oncologists, since it reviews not only the clinical applications of the leukolysins, but presents a current update on those leukolysins that are in early developmental stages of research and could enter into clinical trials in a few years. The introduction gives an overview of the status of research on the leukolysins. In the first section, the biological activities and biochemical characteristics of the leukolysins are presented. The lymphokines.

Laymen often consider modern laboratory research to be based on an endless array of sophisticated technologies whose complex capabilities are as important to the outcome of any project as the inventiveness and creativity of the scientists who employ them. Scientists at times may share this point of view until they are con­ fronted by unexpected findings that demand new approaches, and they discover that yesterday's "sophisticated tools" are today's "blunt instruments." This experience provides a more sobering view of the current state of our scientific methods. It also serves as an impetus for the further development of technology that prepares us for the next stage of advance. Immunologists were confronted by such a technological crises in the late 1970s when they finally were forced to admit that poly­ clonal antibodies, although quite sensitive reagents, were not spe­ cific enough to answer many of the questions then confronting virologists and tumor biologists. The answer to the need for specific­ ity came with the development of monoclonal antibody technology. In the last ten years there have been considerable advances in monoclonal antibody techniques. Today these reagents are much more versatile than they were initially and can be applied to a broad range of problems. Still, most workers who are using these anti­ bodies are convinced that their potential is far from exhausted, and that at least in some fields we are currently in the early stages of learning how to use them properly.

Cancer has become the most critical health problem in the United States. It is expected that 25% of the people will develop this dread disease, and many of these will die from the malady. The causes of cancer are varied, but the best estimate available is that 70--90% arise from environmental factors. These statistics have triggered widespread governmental action along two lines: (l) An effort to identify those chemicals and conditions that give rise to malignant processes has been mounted by the Carcino­ genesis Testing Program, the National Cancer Program, and subse­ quently, the National Toxicology Program. (2) Regulatory laws have been enacted that are administered by agencies such as TSCA, FIFRA, EPA, FDA, OSHA, and so on, whose mission is to minimize public ex­ posure to carcinogens. Since direct verification that specific chemicals induce cancer in hu­ of unanticipated expo­ mans is necessarily limited to known incidences sure and is therefore rare, most chemicals are identified as carcinogens only by laboratory experiments. At present, the only accepted procedure is long-term animal bioassay, and not only are these studies expensive and time-consuming, but current worldwide resources permit the evalua­ tion of only 300-400 chemicals per year, a miniscule amount compared to what is available in the commercial world: 30,000 existing chemicals, with approximately 700 new such materials being introduced every year.

In organizing the present volume, we had two intentions. The first was to present the best current understanding of the mechanisms of calcium mobilization during excitation­ contraction coupling of smooth muscle at a level suited to the needs of professionals interested in smooth muscle pharmacology and pathophysiology, while remaining appreciable by graduate and medical students. The second intention was to provide in­ sight into present-day controversies, as well as the latest ad­ vances achieved by researchers in this field. Thus, we have thor­ oughly discussed both the techniques and the concepts derived from their application. An attempt has also been made here to answer a number of profoundly important questions: What are the mechanisms and agents responsible for the control of contractility? What are the accompanying changes in the state of intracellular calcium ions and the mechanisms responsible for them? How does the regula­ tion of contractility occur directly at the level of the actomyosin activity? What role do gap junctions play in cell-to-cell coupling? What are the roles of cholinergic, adrenergic, peptidergic, and nonadrenergic noncholinergic interactions in calcium mobiliza­ tion in smooth muscle? What changes occur in hypertension? The impact of these recent techniques on future research is also reflected upon.

This represents the third volume in a series on cancer markers pub- lished by the Humana Press. The first volume, published in 1980, stressed the relationship of development and cancer as reflected in the production of markers by cancer that are also produced by normal cells during fetal development. The concept that cancer represents a problem of differentiation was introduced by Barry Pierce in describing differenti- ation of teratocarcinomas. Highlighted were lymphocyte markers, alphafetoprotein, carcinoembryonic antigen, ectopic hormones, enzymes and isozymes, pregnancy proteins, and fibronectin. The second volume, published in 1982 and coedited with Britta Wahren, focused on the diagnostic use of oncological markers in human cancers, which were systematically treated on an organ by organ basis. At that time, the application of monoclonal antibodies to the identification of cancer markers was still in a very preliminary stage. A general introduc- tion to monoclonal antibodies to human tumor antigens was given there by William Raschke, and other authors included coverage of those mark- ers then detectable by monoclonal antibodies in their chapters.

In Cellular Cancer Markers leading pathologists and physicians review today's most promising cellular cancer markers, an important emerging class of prognostic markers that can be used in the clinical evaluation of cancer patients. The markers reviewed have been chosen because they are biologically relevant to the growth of cells and possess an accurate and reproducible assay for detection. They also are predictors of tumor behavior, are useful in making clinical decisions, and are cost effective.Cellular Cancer Markers provides a status report for markers of tumor cell activation, proliferation, and longevity that makes possible an informed judgment regarding the value of many newly proposed tumor markers. It also offers insight into the latest approaches to diagnosing cancer and an appreciation of how these marker-based tests can clarify the prognosis of cancer.