Cancer Growth and Progression – Serie

but also the possibility of intervention in specific stages. In Human behavior, including stress and other factors, plays an important role in neoplasia, although too little is known addition, variables which affect cancer development as well on the reasons for such development. Carcinogens, which as some endogenous factors can be better delineated help initiate the neoplastic process, may be either synthetic through such investigations. The topics of this volume encompass premalignant non­ or naturally-occurring. Cancer causation may be ascribed to invasive lesions, species-specific aspects of carcinogenicity, certain chemicals, physical agents, radioactive materials, viruses, parasites, the genetic make-up of the organism, and radiation, viruses, a quantum theory of carinogenesis, onco­ bacteria. Humans, eumetazoan animals and vascular plants genes, and selected environmental carcinogens. are susceptible to the first six groups of cancer causes, whe­ reas the last group, bacteria, seems to affect only vascular plants. Neoplastic development may begin with impairment ofJmdy defenses by a toxic material (carcinogen) which acts as an initiator, followed by promotion and progression to an overt neoplastic state. Investigation of these processes Series Editor Volume Editor allows not only a better insight into the mechanism of action Hans E. Kaiser Elizabeth K. Weisburger 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.

Recent experimental evidence has made it increasingly clear In particular, this volume reviews the discrete steps involved that the properties of invasive, malignant cells during tumor in metastatic invasion: the interaction of invasive tumor cells development substantially impact on the host. This is under­ with extracellular matrices, the basement membrane, attach­ scored by a variety of biochemical properties of tumor cells ment to extracellular matrices, local proteolytic degradation during their differentiation and metastatic dissemination. of matrices, and the locomotion of invasive tumor cells These properties can be analyzed at different stages of tumor through such areas of localized degradation. The critical growth and progression and this volume explores the role of the cell surface in secondary tumor formation is characteristics of primary tumors as well as the shared reviewed as are important advances in the molecular biology characteristics of both primary and secondary tumors. of metastasis initiation and maintenance. Recent advances The primary tumor comes into existence following in the role of DNA methylation in the generation of tumor preneoplastic biochemical and cellular events that ultimate­ cell heterogeneity and tumor progression are also critically ly result in malignant transformation. Various aspects of summarized. Chapters in this volume also review molecular metabolism, predetermined by nutritional status, often play aspects of metastatic progression, and the use of the tech­ a basic role. Obesity, for example, is cancer-promoting. Cell nologies of DNA transfection and somatic cell fusion in the surface carbohydrates, cytoskeletal proteins, glycoproteins, exploration of molecular aspects of metastatic progression.

It is widely recognized that the host response to tumor munotherapy of experimental metastases in animal systems progression is an important determinant in cancer growth which are beginning to be developed for ultimate clinical and progression. Indeed, as indicated in Volume I of this trials of human cancer metastasis. series, the process of cancer growth and progression, leading This volume explores a variety of host properties that to tumor invasion and metastasis, is dependent upon the influence tumor development including dormancy, regress­ complex, dynamic interactions between the properties of the ion, and recurrence. In addition, current knowledge of the tumor as well as the properties of the host. While Volume III response of the central nervous system to cancer, cardiac of this series reviews in great detail the influence of tumor and pulmonary complications, dermatologic effects and development on the host, this volume emphasizes the in­ hematologic complications of malignancies is presented. fluence of the host on tumor development. These host re­ The endocrine and metabolic function of cancer patients, as sponses include host anti-tumor immune reactivity, tumor well as the production of hormones by tumors is also review­ dormancy, cachexia, multiple endocrine and paraneoplastic ed.

This volume reviews our current knowledge concerning can­ Several chapters discuss the contributions of genetic asp­ cer growth and progression as it relates to the etiology of ects, metabolism, endocrine-related aspects and nutrition to human cancer. As emphasized in Volumes I-V of this series, cancer progression. Moreover, our current knowledge con­ neoplastic diseases are multistep maladies. There are many cerning urbanization factors, radiation, therapy-induced causes for the appearance of neoplastic diseases. Earlier neoplasms, environmentally induced neoplasms (e. g. , chapters in the series have reviewed molecular and cellular mesotheliomas induced by asbestos) and malignant neo­ aspects of tumor initiation, promotion and progression to plasms in organ transplant recipients are summarized. the invasive and metastatic phenotype. Contributions to the The impact of AIDS on neoplasm development is re­ initiation and progression of neoplastic diseases are made by viewed from an epidemiologic perspective that explores mul­ natural features of the environment and by its contaminants tiple facets of immunity, infectious disease, sexual behavior and by nutritional factors. Neoplastic diseases show a dis­ and blood transfusion. Other chapters investigate the in­ tinct relationship to a variety of environmental stimuli and fluence of the host immune response in oncogenesis and the to diseases of a non-neoplastic nature. For example, familial relationship between atherosclerotic plaques and tumors.

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.

Previous volumes in this series have discussed the current progression have identified a variety of targets and strategies state of our knowledge concerning the pathophysiology of to allow these goals to be realized. This volume critically cancer growth and progression. The complexity of the in­ reviews approaches towards cancer management in man at teraction of malignant neoplasms and the host, the the levels of: detection, diagnosis, surgery, radiology, heterogeneity of malignant cell subpopulations, and the chronobiology and endocrine treatment. existence of metastatic tumor cells resistant to drug thera­ Several chapters review selected methods of cancer diag­ pies remain as significant clinical challenges to clinical on­ nosis. In addition, a variety of on-going and novel ap­ cologists. Indeed, conventional treatment regimens of che­ proaches for cancer treatment are also presented in this volume. Progress in the early detection of malignant neo­ motherapy, surgery and radiology are often ineffective for the therapy of a large variety of established metastatic can­ plasms, coupled with novel approaches for the therapy of cer in patients. When one considers the insidiousness of such neoplasms, may ultimately yield safe and well-tolerated agents for the selective therapy of solid malignancies. New progressive neoplastic growth and the emergence of con­ tinuously more aggressive and malignant cellular subpop­ therapeutic approaches, directed towards the biochemical ulations one is overwhelmed with the challenges inherent in and molecular targets identified in the earlier volumes of this series, may ultimately lead to the generation of new mo­ attempting to control malignant neoplasms.

Our work began where the greatest classical morphologists left off; their best work was the start of ours. As our work progressed, the rigidity of basic, previous embryological principles was broken down as scientific knowledge advanced. At the same time, the molecular, biological characterization of the cell surface receptor systems progressed enormously with the invention of numerous monoclonal antibodies. Thus, thymology became once again very important because the thymus is the first and central organ of the human immunological system. Then, the question of immuno-neuroendocrine regulation arose and has only been partially answered. Our book seeks to explore what has not been explored. The topic of thymic epithelial cells is a unique one and has never been explored in any previous book as it is explored in this one. Only a handful of great thymologists remain in the world today, especially after the great loss the medical community suffered with the passing of Dr. Good, the list includes but is not limited to: Dr. Ritter and Dr. Kendall in England, Dr. Savino in Brazil, Dr. Dardenne in France, Dr. von Gaudecker in Germany, a few others in Belgium and Holland, and it is our hope that Dr.Bodey is among them. Nonetheless, a book on the thymus has not been written in the last five years and a book such as this one has never been. This book is based on a 30-year period of research and includes references from a broad range of sources spanning the globe and all sources, even those that were the beginning of thymic research. The book, thus, is uniquely well rounded, more so that previous works.

The present multi-volume Book Series, CANCER GROWTH AND PROGRESSION, encompasses the widest possible framework of cutting edge research in the field of neoplastic pathology and other integrated fields. Normal and pathologic growth is one of the most intensively studied yet challenging areas in pathology. Thus the individual volumes in this series focus on the topics of highest scientific interest for basic and clinical researchers, pathologists, medical and surgical oncologists and allied multidisciplinary teams interested in the study of these aspects of neoplastic growth, progression and inhibition. The range of topics covered is extensive, including but not limited to autonomous growth characteristics of malignancy, phenomena of progression of malignant growth involving the various body systems, and recent advances being made in successful neoplastic inhibition and control. Cell function may be described as producing progression or regression, often found as alternating features in tumors or as variations between normal tissues and tumors. The source of regression in normal melanin producing cells may not be the same as in melanomas. These functions of living matter persist in all phyla of eumetazoans vascular plants as well as in particular species of fungi. However, homo sapiens are the eumetazoan species, which interest us the most. Normal growth processes cannot be entirely understood in all its diversity until we have a thorough knowledge of what constitutes normal growth in various organisms.

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 motilityRole of tumor-cell adhesion and migration in organ-selective metastasis-formationTumor heterogeneity in relation to invasion and metastasis and its clinical implicationsTumor angiogenesis, angioprevention, anti-angiogenic therapies and responseRole of apoptosis in the development, progression and therapy of cancerRole of macrophages in tumor development and metastasisPathways of macrophage-mediated tumor progressionAbnormal variation of immune response against cancerImmunological aspects of Marek’s disease virus (MDV)-induced lymphoma progressionA biodynamical model of human T-cell proliferative disordersCurrent methodologies for characterization of tumor directed immune response.

Thisvolumeisacontinuationoftheencyclopedicworkentitled"CancerGrowthand Progression,"thatwasoriginallyeditedbyProfessorHansE. Kaiser. Asatributeto thememoryofDr. Kaiserandhiscontributionstothe eld,thisneweditionisf- lowinghisexampleofprovidingthemostcurrentinformationaboutcancerliterature andcomprehensivecoverageofallaspectsoftumorgrowthandprogression. Thisparticulartomeisdividedintotwosections:the rstaddressinggeneralcauses ofoncogenesissuchasenvironmentalfactorsandtumormechanisms;andthesecond addressingtheoncogenicmechanismsoftumorinspeci corgans. Thisbookiswr- tenandcompiledbyworldrenownedleadersintheirrespective eldsandfocuseson themostrecentdevelopmentsinbasiconcogenesis. Thisde nitivetextwillprovide thepractitioner,whetherinresearch,academiaorclinicalpractice,withafountof easilyaccessibleinformationonthemostcommontumors. v Contents 1 Cytokines and Stressors: Implications for Cancer Immunotherapy 1 AlexanderW. KusnecovandHymieAnisman 2 The Role of Oncogene Activation in Tumor Progression...19 MichaelJ. GrayandGaryE. Gallick 3 Carcinogenic Effects of Ionising Radiation...43 ArthurC. Upton 4 Chemical Carcinogenesis Role of Chloroform - Further Studies. . 63 ElizabethK.Weisburger 5 Use of Organ Explant and Cell Culture in Cancer Research ...71 EricJ. Kort,ChristineR. Moore,EricA. Hudson, BrandonLeeser,JamesH. Resau,G. M. Yerushalmi, R. Leibowitz-Amit,GaliaTsarfaty,IlanTsarfaty,andSharonMoskovitz 6 Chromosomal Abnormalities in Selected Hematopoietic Malignancies Detected by Conventional and Molecular Cytogenetics: Diagnostic and Prognostic Signi cance...89 HonFongL. Mark,SusanaC. Raimondi,andRobertSokolic 7 Mechanisms of Cancer Growth and Progression in Lymphoma...115 MojdehNaghashpourandLynnC. Moscinski 8 Pediatric Cancer Mechanisms of Cancer Growth and Progression . 129 EnidGilbert-BarnessandPawiniKhanna 9 Carcinogenetic Pathway of Malignant Melanoma ...149 KennethB. CalderandMichaelB. Morgan 10 Ewing Sarcoma: Molecular Characterization and Potential Molecular Therapeutic Targets ...159 MarilynM. BuiandPaulJ. Zhang 11 Molecular Mechanisms of Central Nervous System Metastasis...167 NicoleD. Riddle,MumtazVRojiani,StevenBrem, andAmynM. Rojiani 12 Carcinogenesis of Human Papillomavirus in Head and Neck Squamous Cell Carcinoma...179 DahuiQin vii viii Contents 13 Postmenopausal Hormone Replacement Therapy and Breast Cancer - Clinicopathologic Associations and Molecular Mechanisms ...187 GezaAcsandMichaelJ. Wagoner 14 Carcinogenesis of Lung Cancer ...203 JeffreyAufmanandFarahKhalil 15 Genesis of Barrett's Neoplasia: Current Concepts...213 DomenicoCoppola,NellyA. Nasir,andLeslieTurner 16 Genesis of Pancreatic Ductal Neoplasia...225 BarbaraA. CentenoandGregoryM. Springett 17 Recent Advances in the Pathogenesis of Pancreatic Endocrine Neoplasms...237 OmieMills,NellyA. Nasir,JonathanR. Strosberg, LarryK.

Our work began where the greatest classical morphologists left off; their best work was the start of ours. As our work progressed, the rigidity of basic, previous embryological principles was broken down as scientific knowledge advanced. At the same time, the molecular, biological characterization of the cell surface receptor systems progressed enormously with the invention of numerous monoclonal antibodies. Thus, thymology became once again very important because the thymus is the first and central organ of the human immunological system. Then, the question of immuno-neuroendocrine regulation arose and has only been partially answered. Our book seeks to explore what has not been explored. The topic of thymic epithelial cells is a unique one and has never been explored in any previous book as it is explored in this one. Only a handful of great thymologists remain in the world today, especially after the great loss the medical community suffered with the passing of Dr. Good, the list includes but is not limited to: Dr. Ritter and Dr. Kendall in England, Dr. Savino in Brazil, Dr. Dardenne in France, Dr. von Gaudecker in Germany, a few others in Belgium and Holland, and it is our hope that Dr.Bodey is among them. Nonetheless, a book on the thymus has not been written in the last five years and a book such as this one has never been. This book is based on a 30-year period of research and includes references from a broad range of sources spanning the globe and all sources, even those that were the beginning of thymic research. The book, thus, is uniquely well rounded, more so that previous works.

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 motilityRole of tumor-cell adhesion and migration in organ-selective metastasis-formationTumor heterogeneity in relation to invasion and metastasis and its clinical implicationsTumor angiogenesis, angioprevention, anti-angiogenic therapies and responseRole of apoptosis in the development, progression and therapy of cancerRole of macrophages in tumor development and metastasisPathways of macrophage-mediated tumor progressionAbnormal variation of immune response against cancerImmunological aspects of Marek’s disease virus (MDV)-induced lymphoma progressionA biodynamical model of human T-cell proliferative disordersCurrent methodologies for characterization of tumor directed immune response.

This book represents a comprehensive description and evaluation of the most up-to-date approaches to cancer management. Each chapter, prepared by leading basic researchers and clinicians, provides an in depth description of a specific method for cancer management. The chemotherapy section of the book is updated to include the newest drugs as well as those currently in development. Organized by drug class, this section provides the latest information on most drugs, including their mechanisms of action, interactions with other agents, toxicities, side effects, and mechanisms of resistance. The biological therapy section of the book provides expanded coverage of the currently used cytokines, vaccines, and cell based therapies of cancer. Full consideration is also given to other modern treatment approaches, such as tyrosine kinase inhibitors, inhibitors of tumor angiogenesis, and the transcatheter management of cancer. Current advances in hyperthermia in cancer treatment, hematologic and nutritional support, bone marrow transplantation, pain management and care of the terminally ill patients with cancer are also presented.In summary, this book provides a comprehensive coverage of the current knowledge on the most innovative, systematic and multidisciplinary approaches to the treatment of patients with cancer.

Thisvolumeisacontinuationoftheencyclopedicworkentitled"CancerGrowthand Progression,"thatwasoriginallyeditedbyProfessorHansE. Kaiser. Asatributeto thememoryofDr. Kaiserandhiscontributionstothe eld,thisneweditionisf- lowinghisexampleofprovidingthemostcurrentinformationaboutcancerliterature andcomprehensivecoverageofallaspectsoftumorgrowthandprogression. Thisparticulartomeisdividedintotwosections:the rstaddressinggeneralcauses ofoncogenesissuchasenvironmentalfactorsandtumormechanisms;andthesecond addressingtheoncogenicmechanismsoftumorinspeci corgans. Thisbookiswr- tenandcompiledbyworldrenownedleadersintheirrespective eldsandfocuseson themostrecentdevelopmentsinbasiconcogenesis. Thisde nitivetextwillprovide thepractitioner,whetherinresearch,academiaorclinicalpractice,withafountof easilyaccessibleinformationonthemostcommontumors. v Contents 1 Cytokines and Stressors: Implications for Cancer Immunotherapy 1 AlexanderW. KusnecovandHymieAnisman 2 The Role of Oncogene Activation in Tumor Progression...19 MichaelJ. GrayandGaryE. Gallick 3 Carcinogenic Effects of Ionising Radiation...43 ArthurC. Upton 4 Chemical Carcinogenesis Role of Chloroform - Further Studies. . 63 ElizabethK.Weisburger 5 Use of Organ Explant and Cell Culture in Cancer Research ...71 EricJ. Kort,ChristineR. Moore,EricA. Hudson, BrandonLeeser,JamesH. Resau,G. M. Yerushalmi, R. Leibowitz-Amit,GaliaTsarfaty,IlanTsarfaty,andSharonMoskovitz 6 Chromosomal Abnormalities in Selected Hematopoietic Malignancies Detected by Conventional and Molecular Cytogenetics: Diagnostic and Prognostic Signi cance...89 HonFongL. Mark,SusanaC. Raimondi,andRobertSokolic 7 Mechanisms of Cancer Growth and Progression in Lymphoma...115 MojdehNaghashpourandLynnC. Moscinski 8 Pediatric Cancer Mechanisms of Cancer Growth and Progression . 129 EnidGilbert-BarnessandPawiniKhanna 9 Carcinogenetic Pathway of Malignant Melanoma ...149 KennethB. CalderandMichaelB. Morgan 10 Ewing Sarcoma: Molecular Characterization and Potential Molecular Therapeutic Targets ...159 MarilynM. BuiandPaulJ. Zhang 11 Molecular Mechanisms of Central Nervous System Metastasis...167 NicoleD. Riddle,MumtazVRojiani,StevenBrem, andAmynM. Rojiani 12 Carcinogenesis of Human Papillomavirus in Head and Neck Squamous Cell Carcinoma...179 DahuiQin vii viii Contents 13 Postmenopausal Hormone Replacement Therapy and Breast Cancer - Clinicopathologic Associations and Molecular Mechanisms ...187 GezaAcsandMichaelJ. Wagoner 14 Carcinogenesis of Lung Cancer ...203 JeffreyAufmanandFarahKhalil 15 Genesis of Barrett's Neoplasia: Current Concepts...213 DomenicoCoppola,NellyA. Nasir,andLeslieTurner 16 Genesis of Pancreatic Ductal Neoplasia...225 BarbaraA. CentenoandGregoryM. Springett 17 Recent Advances in the Pathogenesis of Pancreatic Endocrine Neoplasms...237 OmieMills,NellyA. Nasir,JonathanR. Strosberg, LarryK.

This book represents a comprehensive description and evaluation of the most up-to-date approaches to cancer management. Each chapter, prepared by leading basic researchers and clinicians, provides an in depth description of a specific method for cancer management. The chemotherapy section of the book is updated to include the newest drugs as well as those currently in development. Organized by drug class, this section provides the latest information on most drugs, including their mechanisms of action, interactions with other agents, toxicities, side effects, and mechanisms of resistance. The biological therapy section of the book provides expanded coverage of the currently used cytokines, vaccines, and cell based therapies of cancer. Full consideration is also given to other modern treatment approaches, such as tyrosine kinase inhibitors, inhibitors of tumor angiogenesis, and the transcatheter management of cancer. Current advances in hyperthermia in cancer treatment, hematologic and nutritional support, bone marrow transplantation, pain management and care of the terminally ill patients with cancer are also presented.In summary, this book provides a comprehensive coverage of the current knowledge on the most innovative, systematic and multidisciplinary approaches to the treatment of patients with cancer.

In the last decade, there has been a remarkable explosion of knowledge in hematologic cancer from basic molecular biology and pathology to clinical therapy. This has led to many new advance and insights in the understanding of pathobiology of malignant hematology. New knowledge of disease molecular pathology, cytogenetic, epigenetic and genomic alterations have provided new strategies to attack and eradicate tumor cells at molecular level and significantly impacted our current therapeutics for hematological malignancies. The recent and ongoing rapid expansion of knowledge in this area has become extensive, dynamic and diffuse over the literature and research publications. This has led to the need to capture and compile the new and current information about hematologic cancer with special emphasis on translation from molecular pathobiology to targeted therapeutics. In this book experts from around the world share their thoughts and knowledge about the pathobiology of hematologic cancer,as well as their view on current treatment approaches and future development in these malignant hematologic diseases. This book is well suited for hematology residents, fellows and hematology-oncology physicians, hematopathologist as well as basic research scientist in the area of hematologic malignancies.

Molecular pathology is based on the emergence of new techniques that greatly enhance the diagnostic accuracy when facing with challenging differential diagnoses. In addition, new molecular techniques are entering the clinical arena for their value in predicting therapy response and tumor prognosis. This book provides a guide for the practicing pathologist and for both pathology residents and fellows during the daily sign-out of challenging cases. The book is organized by anatomical systems and provides a detailed description of molecular tests that may help in the diagnosis. Furthermore, a description of the current molecular tests required to identify patients for treatment is offered. The application of molecular pathology techniques to the clinical practice has already shown its usefulness and the number of such tests is growing exponentially as more molecular targets are discovered. Molecular Pathology and Diagnostics of Cancer will give practicing and training pathologists an up-to date resource to guide the correct management of pathology cases requiring molecular testing.

The present multi-volume Book Series, CANCER GROWTH AND PROGRESSION, encompasses the widest possible framework of cutting edge research in the field of neoplastic pathology and other integrated fields. Normal and pathologic growth is one of the most intensively studied yet challenging areas in pathology. Thus the individual volumes in this series focus on the topics of highest scientific interest for basic and clinical researchers, pathologists, medical and surgical oncologists and allied multidisciplinary teams interested in the study of these aspects of neoplastic growth, progression and inhibition. The range of topics covered is extensive, including but not limited to autonomous growth characteristics of malignancy, phenomena of progression of malignant growth involving the various body systems, and recent advances being made in successful neoplastic inhibition and control. Cell function may be described as producing progression or regression, often found as alternating features in tumors or as variations between normal tissues and tumors. The source of regression in normal melanin producing cells may not be the same as in melanomas. These functions of living matter persist in all phyla of eumetazoans vascular plants as well as in particular species of fungi. However, homo sapiens are the eumetazoan species, which interest us the most. Normal growth processes cannot be entirely understood in all its diversity until we have a thorough knowledge of what constitutes normal growth in various organisms.

In the last decade, there has been a remarkable explosion of knowledge in hematologic cancer from basic molecular biology and pathology to clinical therapy. This has led to many new advance and insights in the understanding of pathobiology of malignant hematology. New knowledge of disease molecular pathology, cytogenetic, epigenetic and genomic alterations have provided new strategies to attack and eradicate tumor cells at molecular level and significantly impacted our current therapeutics for hematological malignancies. The recent and ongoing rapid expansion of knowledge in this area has become extensive, dynamic and diffuse over the literature and research publications. This has led to the need to capture and compile the new and current information about hematologic cancer with special emphasis on translation from molecular pathobiology to targeted therapeutics. In this book experts from around the world share their thoughts and knowledge about the pathobiology of hematologic cancer,as well as their view on current treatment approaches and future development in these malignant hematologic diseases. This book is well suited for hematology residents, fellows and hematology-oncology physicians, hematopathologist as well as basic research scientist in the area of hematologic malignancies.

Individual neoplastic diseases often show discrete growth direct effect of tumor metastases or to adverse consequences patterns subject to many modifications according to the associated with these therapeutic modes (e.g., complications stage of the disease, the species involved and the tumor type of immunosuppression which can lead to mortality arising concerned. Primary neoplasms are less difficult to treat in from infectious disease). contrast to secondary neoplasms. The chief type of secon­ It is therefore quite clear that there is a crucial need for dary neoplastic growth, metastasis, is also comparatively new methods for the detection of micrometastases and the development of new modalities for the treatment of estab­ less well understood. Phylogenetically, metastasis attains its highest level of development in the mammal and is best lished metastases. It is likely that such modalities must known in man, but is still far from being understood. overcome tumor heterogeneity and drug resistance to yield new therapeutic modalities with improved margin of safety The process of cancer growth and progression, from the initiation of neoplastic transformation of normal cells to the and efficacy over currently available anti-neoplastic drugs.

of the interaction and relationship of both systems is chal- In this volume, aspects of neoplastic spread, already elu- cidated in Volumes I-IV of this series, are considered lenging indeed. against a broad biological background. The mammalian The volume also reviews environmental oncology and species-specific aspects of environmental chain reactions. It orders constituting the logical framework for man as focal point of a comparative oncology are reviewed. Selected is apparent that the environment plays a significant role in examples of neoplastic progression in various taxonomic the development of neoplasms. Neoplasms among the spe- units are provided, beginning with the opposite pole of ci es have become much more common as a result of man's taxonomic development, the vascular plants, where no impact on the environment. The latter chapters present a metastatis of malignant neoplasms occur. Among in- brief review of geologic and technologic and cuItural vertebrates, vertebrates, and vascular plants, Iining mem- changes, and the implications of species-specific cancer pro- branes (epithelia) exhibit the highest degree of comparabil- gression.The remainder of this section outlines a number of ity. Metastases also occur, but more rarely, in invertebrates; selected chain reactions leading to neoplastic development and are discussed as they are found in the nonmammalian in certain members of these chains. A discussion of the vertebrates: in fish, amphibians, reptiles, and birds. Diseases storage of chemical carcinogens in plants and their interac- ofthe leukemia (Ieucosis)-Iymphoma complex are present in tion with other causes of neoplastic growth is also included.

In this volume the process of local invasion and the spl~ad cies, myeloid leukemias, histiocytic tumors, eosinophilic is emphasized. Volumes I-VI have already provided know- granulomas, and systemic mastocytosis. ledge pertaining to the importance of tumor invasion and The exploration of local recurrence of neoplasms, and the metastasis in the morbidity and mortality of human neo- relationship of recurrence to tumor dormancy, is reviewed plasms. as it relates to local tumor invasion and progression to The characteristics of local, direct tumor spreading at metastasis. The elucidation of the mechanisms underlying various sites, including head and neck, the coelomic surface, local tumor invasion and tumor recurrence, as well as those and neuroendocrine tumors are presented.Emphasis is maintaining tumor dormancy oflocal neoplasms or dissemi- placed on the spreading of neoplasm by implantation on nated micrometastases, will not only lead to advances in the epithelial surfaces, the spread of occult primary malignan- early detection and treatment of primary neoplasms but also cies, and rare types of neoplastic progression, as well as detection and eradication of disseminated metastatic foci. neoplasms of the immune system, the progression of lymphoproliferative disorders and hematologic malignan- Series Editor Volume Editor Hans E. Kaiser Kenneth W. Brunson Vll 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.

This volume, the last in this series on cancer growth and Moreover, the current status of plant-derived vinca alka­ progression, is a companion volume to Volume IX and loids and non-alkaloid natural products is summarized. further explores established and novel approaches for the Advances in hyperthermia and additional approaches for therapy of patients with malignant neoplasms. The stra­ the therapy of malignancies are also presented. tegies reflected in these volumes are direct extrapolations The volume continues with chapters on bone marrow from the basic science of cancer biology, growth and pro­ transplantation as well as hematologic and nutritional sup­ gression described in earlier volumes of this series. Some port for the cancer patient. Blood pressure in the cancer approaches are directed towards the eradication or modifi­ patient, therapy for nausea and vomiting as well as pain are cation of the properties of heterogeneous malignant tumor discussed. The last chapter is devoted to the problems of the cells at various stages of tumor progression, while other terminally ill, including evaluations of the burden relatives approaches are directed towards modification of the host and friends of the cancer patient have to bear. antitumor defense systems, e. g. , enhancement of host anti­ It is clear that important advances in the basic science of tumor immune reactivity.

Contributions to the The impact of AIDS on neoplasm development is re­ initiation and progression of neoplastic diseases are made by viewed from an epidemiologic perspective that explores mul­ natural features of the environment and by its contaminants tiple facets of immunity, infectious disease, sexual behavior and by nutritional factors.

Previous volumes in this series have discussed the current progression have identified a variety of targets and strategies state of our knowledge concerning the pathophysiology of to allow these goals to be realized. This volume critically cancer growth and progression. The complexity of the in­ reviews approaches towards cancer management in man at teraction of malignant neoplasms and the host, the the levels of: detection, diagnosis, surgery, radiology, heterogeneity of malignant cell subpopulations, and the chronobiology and endocrine treatment. existence of metastatic tumor cells resistant to drug thera­ Several chapters review selected methods of cancer diag­ pies remain as significant clinical challenges to clinical on­ nosis. In addition, a variety of on-going and novel ap­ cologists. Indeed, conventional treatment regimens of che­ proaches for cancer treatment are also presented in this volume. Progress in the early detection of malignant neo­ motherapy, surgery and radiology are often ineffective for the therapy of a large variety of established metastatic can­ plasms, coupled with novel approaches for the therapy of cer in patients. When one considers the insidiousness of such neoplasms, may ultimately yield safe and well-tolerated agents for the selective therapy of solid malignancies. New progressive neoplastic growth and the emergence of con­ tinuously more aggressive and malignant cellular subpop­ therapeutic approaches, directed towards the biochemical ulations one is overwhelmed with the challenges inherent in and molecular targets identified in the earlier volumes of this series, may ultimately lead to the generation of new mo­ attempting to control malignant neoplasms.