Rectal Cancer: International Perspectives on Multimodality Management is a timely analysis of the diagnosis, staging, pathology, and therapy of cancer of the rectum. This book is intended as a useful resource for physicians, scientists, medical students, and allied health personnel in the disciplines of radiology, gastroenterology, surgical oncology, medical onc- ogy, radiation oncology, and pathology. Renowned contributors from different medical d- ciplines have written their chapters in a thoughtful, provocative, and visual fashion. Importantly, these chapters highlight the controversies in the diagnostic, staging, and the- peutic management of patients with rectal cancer while providing practical management recommendations. This book is divided into 18 chapters. Early chapters address the diagnosis and staging of rectal cancer, highlighting the critical role of contemporary imaging in guiding treatment. The remaining chapters focus on the multimodality management of rectal cancer from the vantage points of surgery, pathology, chemotherapy, and radiation therapy. The major dev- opments in surgery are reviewed first, including contemporary roles of local excision, total mesorectal excision, lateral pelvic lymph node dissection, organ preservation approaches, as well as the management of advanced, recurrent, and metastatic disease. Following is a ch- ter describing the pathologic evaluation of rectal cancer specimens, with emphasis on proper methodology and its clinical relevance to overall disease management. The final chapters review the contemporary roles of chemotherapy (including with radiation therapy, adjuvant and neoadjuvant settings without radiation therapy, as well as in metastatic disease) as well as radiation therapy (including adjuvant and neoadjuvant approaches, short vs.

Malignant neoplasms occurring in the biliary tract and pancreas remain a therap- tic challenge. The mechanism of carcinogenesis as well as the growth and spread of these tumors is still poorly understood, making the development of rational tre- ment strategies difficult. In order to improve the clinical results achieved by sur- cal or other medical treatment of such malignant tumors, the establishment of an experimental animal model is critical. For this purpose, attempts were made to induce carcinoma experimentally in the biliary tree and finally an animal model using the hamster was established in 1994 at our laboratory. Because the tumor in this model mimicked the characteristics of human tumors, a series of experimental investigations were conducted to clarify the pathological characteristics of biliary carcinoma, the genetic alterations during biliary carcinogenesis, and the relationship between biliary inflammation and c- cinogenesis. The chemopreventive effects on the occurrence of biliary carcinoma were also successfully examined. In addition, in vitro studies led to the establi- ment of transplantable biliary cancer cell lines and biliary epithelial cell lines by utilizing the hamster model. This monograph represents the collective efforts in hepato-biliary and pancreatic disease research over the past 20 years. I hope that this monograph will be a source of useful knowledge for basic researchers as well as for clinicians involved in the care of patients with hepato-biliary and pancreatic neoplasms. Takashi Kanematsu, M.D., Ph.D.

This comprehensive, yet practical, text is a ready collection of the most up-to-date information on primary CNS tumors. Authored by a carefully selected group of the world's leading clinicians and scientists, the book is divided into three sections. The opening chapters cover general principles, including epidemiology, pathogenesis, tumor stem cells, supportive care, complications of therapy, and quality of life. The remaining two sections are comprised of treatment-oriented chapters covering the spectrum of gliomas and rarer tumor types. Each of these chapters presents multi-disciplinary therapeutic approaches and addresses specific disease concerns. Throughout, the authors incorporate the cutting-edge advances in molecular biology and genomics that are revolutionizing neuro-oncology. The result is an important clinical resource which provides evidence-based data and interpretation essential to intelligent therapeutic decision making.

This practical collection examines methodologies originating from the benefits of genome-wide approaches to studying epigenetics, which has opened the emerging field of epigenomics. Focusing on the areas of cancer, inflammatory and autoimmune disorders, chapters discuss three main components of the epigenome and their role in the regulation of gene expression and present a detailed method section specific to studying each component, including data analyses, troubleshooting, and feasibility in different experimental settings. The main topics are high-throughput and targeted methods for DNA methylation analysis, nucleosome position mapping, studying epigenetic effects of gut microbiota, optical imaging for detection of epigenetic aberrations in living cells, methods for microRNA, and histone code profiling. Written for the Methods in Pharmacology and Toxicology series, the book includes the kind of detail and implementation advice to encourage success in the lab. Authoritative and easily applicable, Epigenetics and Gene Expression in Cancer, Inflammatory and Immune Diseases aims to provide pharmacologists, molecular biologists, bioinformaticians, and toxicologists with a vital background on epigenetics and state-of-the-art techniques in epigenomics.

Precis This book is a treatise about the origin of cancers. I would like to convince readers that the basic tenets of the theory of a stem-cell origin of cancers also constitute a unified theory of cancer. Stem-cell origin of normal (and cancer) cells: Vitruvian version Every truth passes through three stages before it is recognized. In the first it is ridiculed, in the second, it is opposed, in the third, it is regarded as self-evident. - Arthur Schopenhauer v vi Preface Every person has a unique story to tell. My story is about cancer. Cancer touches the lives of countless people. Often enough, it leaves indelible tracks. Many lives have been lost; others are forever changed. For those who confront this deadly scourge, there is a sense of urgency, if not of desperation. For those who face im- nent death, life becomes even more precious and carries a special meaning. As an oncologist, I am touched daily by cancer. I feel its inception, evolution, and aft- math. It seems as though we are fighting an incessant war against cancer at the front line in the trenches. This is my story about cancer. Some people are terrific storytellers. Others have incredible tales to tell.

The Von Hippel-Lindau Tumor Suppressor Complex and Regulation of Hypoxia -Inducible Transcription. Retinoblastoma Tumor Suppressor and Genome Sta bility. The Abl Family Kinases: Mechanisms of Regulation an d Signaling. Cellular Immunity to the Her-2/neu Proto-oncog ene. A New Challenge for Successful Immunotherapy by Tumors That Are Resistant to Apoptosis: Two Complementary Signals to Overcome Cross-Resistance. Cell Volume and Ion Changes During Apopt otic Cell Death. Mitochondria and Apoptosis: New Therapeut ic Targets.

Coordinate Regulation of Translation by the PI 3-Kinase and mTOR Pathway s. Histone Acetyl-Transferases and Deacetylases in the Con trol of Cell Proliferation and Differentiation. Molecular Pathogenesis o f Human Hepatocellular Carcinoma. The Cell Mediated Immune Response to Human Papillomavirus Induced Cervical Cancer: Implications for Immunotherapy. The T-cell Response in Patients with Ca ncer. The Life and Death of a B Cell.

Although there are numerous technical-scientific books on breast cancer in the global bibliography, such books deal exclusively with the nature of the disease in majority populations of the Western societies, with little or no reference to the nature of the disease in the minority populations in such societies. Similarly, the nature of breast cancer in black women of the less privileged societies, and in women of ethnic groups living in countries of similar socio-economic status, is virtually unknown. For various epidemiological reasons, breast cancer incidence is rapidly increasing in these counties, more so than currently is the case in developed countries. Thus, the global burden of cancer is shifting gradually to these areas of the world, and may equal or even surpass the breast cancer burden in the Western societies within the foreseeable future. This book is unique because it bucks the trend of virtually all other breast cancer books by addressing specifically the breast cancer experience of women of African descent and their lifestyle counterparts in other societies of the world.

Myelodysplastic syndromes are to the bone marrow what pneumonia is to the lungs; the response of an organ to a variety of etiologic insults like aging, toxic exposure, infections and auto-immunity. Among infectious causes alone, pneumonia could be the result of a variety of possible pathogens including bacterial, viral, tuberculous or fungal agents. Similarly, MDS cannot be treated as a single disease. Attempts to harness the inherent complexity of MDS by devising classifications' which group the various syndromes as one disease is as misguided as saying that a pneumonia is not infectious because it did not respond to antibiotics. Progress in the field will occur faster when we re-analyze this premise. Therefore, until a clearer picture of the disease emerges it is best to treat each of the MDS syndromes as a separate entity. Having no classification is better than a misleading one. Cancer research has been notable for its periodic cycles of promise and hope, followed by defeat and disappointments. It is not that there is no solution, but that the problem has not been identified precisely. This book is our attempt to define the most crucial questions related to MDS that need to be addressed immediately through logic, analysis and rigorous experimentation. If the emerging problems appear daunting, then instead of being overwhelmed by them, we should follow the advice of the great 20th century thinker Antonio Gramsci, pessimism of the intellect must be faced with the optimism of will'.

MALT Lymphomas is a multidisciplinary book that covers all the aspects of MALT lymphomas, from the molecular biology, the aetiology and the pathology, to all the possible therapeutic approaches. Extranodal marginal zone B cell lymphoma of MALT type (MALT lymphoma) is one of the lymphoma subtypes that has allowed us some of the most interesting steps forward in the understanding and treatment of human cancers.

The eight contributions have been written by a team of international experts and represent an essential reading for oncologists, haematologists, gastroenterologists, pathologists and all the other physicians and researchers involved in cancer. The book is also supported by a series of figures illustrating the histology and the clinical features and the treatment.

The thoroughly updated and revised third edition of Management of Prostate Cancer provides concise and authoritative guidance to today's best therapeutic regimens for the diagnosis and treatment of prostate cancer. Highlighting the latest major advances in the field, the book includes chapters on the most controversial areas of prostate cancer - screening, chemoprevention, and active surveillance; updated chapters on genetic risk and progression, biopsy schemes, treatment of complications, and comparative treatment outcomes for surgery; and new chapters on risk factors, new markers, nomograms, and focal therapy. This volume also features overviews of new and emerging drugs and treatment paradigms for castrate resistant disease, advances that promise to extend life and perhaps even cure a subset of men with metastatic disease. With its comprehensive illustrations and contributions from renowned experts in the field, Management of Prostate Cancer, 3rd Edition is an invaluable resource for practitioners in the treatment of prostate cancer.

Tumour-Associated Macrophages are of interest to the cancer research community, and this book is among the first to discuss a definitive theory on the role of macrophage in tumour development. It includes research and intensive discussion of Ik-B and NF-kB.

This thesis focuses on the synthesis and vaccine evaluation of the prostate tumor- associated carbohydrate antigen RM2. The author first presents the use of the [1+2+3] one-pot sequential strategy to successfully synthesise the RM2 antigen and its analogues as single stereoisomers in every glycosylation step, producing good yields and stereoselectivity. He then introduces the conjugation of the synthetic RM2 antigen to the carrier protein CRM197 in an average number of 1-10 to create the prostate cancer vaccine candidate, which is combined with -galactosylceramide C1, its analogue C34, or Alu. The results of the vaccination studies in mice are also described and indicate that the strongest anti-RM2 antigen titer is exhibited when one molecule of diphtheria toxin (DT) is conjugated with an average of 4.7 molecules of RM2 antigen (DT-RM4.7) and adjuvanted with the glycolipid C34. More importantly, the induced mouse antibodies mediate the effective complement-dependent cytotoxicity (CDC) against the prostate cancer cell line LNCap. The study presented in this thesis is the first ever to successfully synthesize this complex glycan molecule. Owing to the steric hindrance of the adjacent sialyl moiety, the introduction of two sialic acid units to the compact and rigid 3,4 di branched galactoside unit is very challenging and the -selective and efficient glycosylation of the galactosamine moiety at the 4-position of di branched galactose is also problematic.

A link between inflammation and cancer has been established many years ago, yet it is only recently that the potential significance of this connection has become apparent. Although several examples of chronic inflammatory conditions, often induced by persistent irritation and/or infection, developing into cancer have been known for some time, there has been a notable resistance to contemplate the possibility that this association may apply in a causative way to other cancers. Examples for such progression from chronic inflammation to cancer are colon carcinoma developing with increased frequency in patients with ulcerative colitis, and the increased incidence of bladder cancer in patients suffering from chronic Schistosoma infection. Inflammation and cancer have been recognized to be linked in another context for many years, i.e., with regards to pathologies resembling chronic lacerations or 'wounds that do not heal.' More recently, the immunology of wound healing has given us clues as to the mechanistic link between inflammation and cancer, in as much as wounds and chronic inflammation turn off local cell-mediated immune responses and switch on growth factor release as well the growth of new blood vessels - angiogenesis. Both of these are features of most types of tumours, which suggest that tumours may require an immunologically shielded milieu and a growth factor-rich environment.

Having been a fairly dormant specialty for many decades, in recent years there has been a remarkable increase in activity in Neuro-oncology from basic science through to the clinics. Reflecting this there have been considerable advancements in the understanding of the biology of CNS malignancies which have infirmed the development of many novel and successful therapies. This work aims to bring together the scattered literature on the new concepts in neuro-oncology for the benefit of those in the field. The book moves from concepts in the scientific basis of neuro-oncology, through to modelling techniques and finishing on the translation into clinical practice.

Chromosomes Today, Volume 13 includes the plenary lectures presented at the 13th International Chromosome Conference, covering the most recent advances in the studies on chromosomes. The contributions in this volume were presented by some of the world's leaders in cytogenetic and molecular research and outline the present status of knowledge on the composition, structure, function and evolution of chromosomes, including, among others, the advancement of the human genome project. The use of cytogenetic studies has greatly increased in the last few years, resulting in a progressive improvement in the available methods that has consequently allowed a more detailed analysis of the molecular organization of eukaryotic chromosomes and a precise in situ localisation of specific gene sequences. This volume of Chromosomes Today provides up-to-date information regarding the topics at the forefront of chromosome research: genetic regulation, imprinting, DNA duplication, meiotic pairing, and the regulation of the...

This book provides a comprehensive and up-to-date review of the relationship between obesity and cancer. It opens with a global perspective on obesity and cancer incidence, followed by in-depth discussions of those cancers for which we have sufficient evidence of a causal relationship with obesity. It addresses topics such as the effects of obesity on cancer incidence and cancer survival, the effects of weight gain and weight loss in adulthood on cancer risk, the effects of childhood and adolescent obesity, and the role of body fat distribution in cancer risk. Individual chapters discuss potential pathways for the observed associations and explore possible mechanisms from both an epidemiological and an experimental perspective. It concludes with a population perspective on the cancer risk that is attributable to obesity and is thus potentially avoidable. This book is of particular value to researchers and epidemiologists and is also of interest to public health workers and clinicians.

approaches to the experimental problems that still face us in understanding this most fascinating of organs. Too many people contributed to the completion of this volume to allow acknowledg ment of all the individual efforts, but we particularly thank the reviewers whose input into the editorial process was invaluable and the authors of these chapters who revised their text, sometimes more than once, to bring it to the high standards set by the Editors. The Com mittee gratefully acknowledges the support ofVysis, Inc. , in the publication of a color figure in Chapter 19, by S. Weber-Hall and Trevor Dale. Finally, we wish to express our heartfelt appreciation to Margot Ip and Bonnie Asch, who worked long and hard to bring this volume to fruition. Margaret C. Neville for the Committee on Mammary Gland Biology Preface One of the most exciting and beneficial developments in research on mammary gland biology and breast cancer has been the influx of increased funding to support this work. This influx, which has been due primarily to the tireless efforts of breast cancer activists to gamer addi tional money from various federal and state sources, has led to a rapid expansion of research efforts by attracting numerous new investigators into the field. These new investigators include students, postdoctoral fellows, and scientists from other fields.

Electroporation is the forefront in tumor ablation. This book presents the basic principles and clinical applications of electroporation, including the latest research results and patient data. A comprehensive approach to the basic science behind the development of this ground-breaking technique and its introduction into clinical practice, the book discusses the entire spectrum of currently available reversible treatments, the emerging irreversible applications, and their impact on patient care. Clinical Aspects of Electroporation is the first book intended for clinicians on this extremely important and rapidly developing field.

The Advances in Cancer Research series provides invaluable information on the exciting and fast-moving field of cancer research. This volume presents outstanding and original reviews on a variety of topics, including gene expression in inherited breast cancer, multiparameter analyses of cell cycle regulation in tumorigenesis, Rho GTPases in transformation and metastasis, the myc oncogene, genetic requirements for the episomal maintenance of oncogenic herpesvirus genomes, treatment of Epstein-Barr virus-associated malignancies with specific T cells, the role of glycogen synthase kinase-3 in cancer, chronic immune activation and inflammation in the pathogenesis of AIDS and cancer, and molecular biology of Hodgkin's lymphoma.
* Gene Expression in Inherited Breast Cancer
* Multiparameter Analyses of CellCycle Regulatory Proteins in Human Breast Cancer: A Key to Definition of Separate Pathways in Tumorigenesis
* Rho GTPases in Transformation and Metastasis
* The "myc" Oncogene: Marvelously Complex
* Genetic Requirements for the Episomal Maintenance of Oncogenic Herpevirus Genomes
* Treatment of Epstein-Barr Virus-Associated Malignancies with Specific T Cells
* Role of Glycogen Synthase Kinase-3 in Cancer: Regulation Wnts and Other Signaling Pathways
* Chronic Immune Activation and Inflammation in the Pathogenesis of AIDS and Cancer
* Molecular Biology of Hodgkin's Lymphoma

Leading experts survey the currently available technologies designed to improve the delivery of today's cancer chemotherapeutic agents. The authors review both the theoretical and practical considerations governing conventional and nonconventional methods of drug administration, and identify promising opportunities for product development. In their outline and discussion of the use of novel formulation technologies-including synthetic polymers and biomaterials for prolonged or sustained drug release to achieve potentially greater therapeutic effect-they profile those technologies that have resulted in a number of approved and late-stage clinical products.

This volume documents this unique family of cell surface proteins. Despite masquerading as intractable and difficult to clone and characterize, ENOX proteins have and continue to offer remarkable opportunities for research, commercial development and outside confirmation of therapeutic, diagnostic and new paradigms to help explain complex biological processes.

Recently the CXCR4/CXCL12-axis has been recognized as one of the pivotal adhesion pathways by which hematopoietic stem cells are retained in the bone marrow. CXCR4 antagonists with different chemical specification are being developed. Pharmacology research guides the way to the rational development effective antagonists. One antagonist, plerixafor, is clinically approved now for stem cell mobilization of lymphoma and myeloma patients. This allows patients to receive potentially life-saving treatment which could not have been administered otherwise. Through early clinical studies it was recognized that CXCR4 antagonists also mobilize malignant hematopoetic cells, i.e. leukemia cells. In preclinical studies a sensitization of mobilized leukemic cells to standard cytotoxic chemotherapy could be shown. Clinical studies are under way. CXCR4 antagonists are an exciting new class of compounds which are also employed for the mobilization of angiogenic cells or for the treatment of solid tumors. In this book a concise review of the current status of knowledge and future developments will be presented.

This book provides a concise, yet comprehensive overview of the many facets relating to human health risk assessments in relation to chemical exposure problems. It presents some very important tools and methodologies that can be used to address chemical exposure and public health risk management problems in a consistent, efficient, and cost-effective manner. On the whole, the book represents a collection and synthesis of the principal elements of the risk assessment process that may be used to more effectively address issues pertaining to human exposures to chemicals found in modern societies. This also includes an elaboration of pertinent risk assessment concepts and techniques/methodologies for performing human health risk assessments. Written for both the novice and the experienced, the subject matter of this book is an attempt at offering a simplified and systematic presentation of public health risk assessment methods and application tools - all these facilitated by a layout that will carefully navigate the user through the major processes involved. A number of illustrative example problems are interspersed throughout the book, in order to help present the book in an easy-to-follow, pragmatic manner.

It has been over a decade since the First International Symposium on Hormonal Carcinogenesis convened in 199 1. Since then, the field has rapidly expanded with considerable progress in both breast and prostate cancers; while ovarian and endometrial cancer have been hampered, in part, due to the absence of suitable hormone-mediated animal models. While knock-out, transgenic, and cell-culture systems have been extremely useful in identifying specific genelprotein alterations and the ensuing pathways affected, the precise molecular mechanisms whereby sex hormones elicit their oncogenic effects still remain elusive. Moreover, despite the considerable progress made in breast cancer research, the exact role of progestins in the presence or absence of estrogen in breast growth, differentiation, and malignant transformation is lacking. Elucidating the incipient molecular alterations in earlylpre-invasive lesions elicited by these hormones is a growing important focus of this field. The main purpose of these Symposia has been to address vital questions that impact our understanding of the causation, dependency, progression, resistance, and prevention of hormonally-associated cancers. We are indebted to the Scientific Advisory Board members who worked with us reviewing and offering suggestions to finalize the scientific program. We offer special thanks for the guidance and support of Dr. Gerald Mueller. His wisdom played an indispensable role in maintaining the excellence of these Symposia. We also acknowledge the numerous external reviewers that worked diligently to revise and improve the quality of the manuscripts. We are very grateful to Ms. Tandria Price.