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.

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."

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.

The power of stem cells for tissue development, regeneration, and renewal has been well known by embryologists and developmental biologists for many years. Those presently active in research in the stem cell field owe much to previous work by embryologists and cancer researchers for their insights into what stem cells can do. In the last 4- 5 years, the rapid expansion of the concept of adult tissue stem cells as pluripotent progenitors for various tissues has led to an even greater appreciation of the power of stem cells. The demonstration that both embryonic and adult tissue stem cells have the ability to produce progenitor cells for tissue renewal has opened vast possibilities for treatment of congenital deficiency diseases as well as for regeneration of damaged tissues. Older concepts of determination leading to loss of potential during differentiation of adult tissues are being replaced by newer ideas that cells with multiple potential exist in different forms in various adult organs and that cells thought to be restricted to differentiation to one cell type may be able to "transdifferentiate" into other tissue cell types. Thus, the concept of "embryonic rests" in adult tissues, hypothesized to be the cellular origin of cancer by Durante and Conheim in the 1870s, now can be expanded to include survival of pluripotential embryonic-like stem cells in adult tissues.

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.

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."

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.

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."

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.

This book discusses critical areas of progress in stem cell research, including the most recent research and applications of pluripotent embryonic cells, induced pluripotent cells, oligopotent tissue stem cells and cancer stem cells. The text covers basic knowledge of stem cell biology, stem cell ethics, development of techniques for applying stem cell therapy, the technology of obtaining appropriate cells for transplantation as well as the role of stem cells in cancer and how therapy may be directed to cancer stem cells. This new volume is essential reading for all scientists currently in the field or allied research areas, and those for those graduate students who envision a career in stem cells.