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.

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...

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

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 book covers the molecular and cellular aspects of cancer metastasis, and discusses the clinical aspect of micro- and macro-metastases, which result in the death of the majority of patients with cancer. The current edition attempts to examine the current status of the basic scientific and clinical research in the area, and is a very useful reference for clinicians, oncologists, and biologists. It is intended for undergraduates as well as postgraduates in the area of medicine, oncology, and cancer biology.

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.

Here in a single source is a complete spectrum of ideas on the development of new anticancer drugs. Containing concise reviews of multidisciplinary fields of research, this book offers a wealth of ideas on current and future molecular targets for drug design, including signal transduction, the cell division cycle, and programmed cell death. Detailed descriptions of sources for new drugs and methods for testing and clinical trial design are also provided.
KEY FEATURES:
* One work that can be consulted for all aspects of anticancer drug development
* Concise reviews of research fields, combined with practical scientific detail, written by internationally respected experts
* A wealth of ideas on current and future molecular targets for drug design, including signal transduction, the cell division cycle, and programmed cell death
* Detailed descriptions of the sources of new anticancer drugs, including combinatorial chemistry, phage display, and natural products
* Discussion of how new drugs can be tested in preclinical systems, including the latest technology of robotic assay systems, cell culture, and experimental animal techniques
* Hundreds of references that allow the reader to access relevant scientific and medical literature
* Clear illustrations, some in color, that provide both understanding of the field and material for teaching

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.

Malignant mesothelioma is an aggressive and fatal neoplasm of serous membranes that still shows a rising incidence worldwide. This book covers all the important aspects of the disease by bringing together contributions from selected experts in the fields of epidemiology, imaging, pathological diagnosis, therapy, genetics, and screening. Special emphasis is placed on the latest diagnostic techniques and current therapy standards. In addition, the mineralogy of asbestos is reviewed and clear advice is included on the analysis of tissue mineral fiber content. By providing a compact, scientifically based, and up-to-date overview of the management of malignant mesothelioma, this volume will be invaluable for all clinicians and pathologists who are engaged in the diagnosis and treatment of the disease or in related research.

Invasive bladder tumors affect the muscle wall, and have a propensity to metastasize and spread to other areas of the body, and are more likely to be fatal. This book presents state-of-the-art diagnoses and treatments available for bladder cancer that has metastasised into the body. A thorough review of current practice is presented in a full color volume with more than 40 tables and 50 illustrations. The book offers a comprehensive review of the subject, covering epidemiology, screening, diagnostic factors, surgery, chemotherapy and post-operative monitoring. Most chapters are jointly written by a basic researcher and a clinician.

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 suppressor and oncogenic roles of TGF-b and its signaling pathways in tumorigenesis, hereditary diffuse gastric disease, the role of heparan sulfate proteoglycans in cell signaling and cancer, V-gene mutations in B-cell-derived human malignancy, MHC antigens and tumor escape from immune surveillance, the role of selection in progressive neoplastic transformation, and the genomic stability, neuronal development, and cancer cross paths of ATM.
*Suppressor and Oncogenic Roles of TGF-aand Its Signaling Pathways in Tumorigenesis
*Hereditary Diffuse Gastric Disease
*Role of Heparan Sulfate Proteoglycans in Cell Signaling and Cancer
*The Occurrence and Significance of V-Vene Mutations in B Cell-Derived Human Malignancy
*MHC Antigens and Tumor Escape from Immune Surveillance
*Foundations in Cancer Research: The Role of Selection in Progressive Neoplastic Transformation
*ATM: Genomic Stability, Neuronal Development, and Cancer Cross Paths

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.

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.

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.

The tiny microRNAs (miRNAs) can have huge impacts on the regulation of a variety of genes and play crucial roles in the fundamental cellular processes. Recent miRNA studies change the landscape of cancer genetics by scrutinizing the alterations of genome-wide miRNA expressions in most common cancers and their regulatory functions during the development of cancer. The connections between miRNAs and cancer are widespread enough to warrant more comprehensive investigations in the systems biology perspective. In MicroRNA and Cancer: Methods and Protocols, internationally renowned experts provide the latest miRNA knowledge, the various techniques and methodologies currently available for cancer research application. Ranging from the fundamental concepts to practical applications, this book presents: * Overview of microRNA biogenesis, computational prediction of new miRNAs in the cancer genome, and miRNA-based therapeutic approaches for cancer treatment * Detailed experimental protocols in miRNA detection with novel and high-throughput technology, miRNA library cloning, miRNA epigenetic regulation, and miRNA pathway study * Stepwise computational and bioinformatic procedures for miRNA complex networks in cancer genomes with a variety of softwares and programs * Cross-cited notes on troubleshooting and avoiding known pitfalls Authoritative and cutting-edge, MicroRNA and Cancer: Methods and Protocols serves researchers with the basic principles of experimental and computational methods for microRNA study in cancer research and provides a firm grounding for those who wish to further develop their own applications and tailor them to their own specific research needs.

The concomitance of cancer and pregnancy is a biological paradox and one of the greatest challenges in the lives of young patients, their partners, and their families. It is also a challenge to oncologists, because the management of the pregnant cancer patient involves both mother and fetus. Ideally, oncologists, reproductive endocrinologists, obstetricians and neonatologists, nurses, and psychologists work within a dedicated multidisciplinary team to deliver optimal cancer therapy to the mother, while assuring fetal well-being.

This book, written by oncology experts with knowledge and clinical expertise on diagnosis, treatment, and follow-up of women with different types of cancer during pregnancy, provides a comprehensive review of existing data on cancer during pregnancy and a general overview of its psychological, ethical, and social aspects. Chapters address the diagnosis, treatment, and follow-up of young women with specific solid or hematologic cancers during pregnancy. The safety of subsequent pregnancy after cancer treatments and the alternatives to maintain or enhance fertility in women undergoing cancer therapy are also addressed. While not intended as a practical guideline, the book contains clinical suggestions, bibliography, and references to available online sources about referral centers, ongoing clinical trials, and tumor registries to help oncologists in the clinic.

This volume provides a general overview of the therapeutic potential of the essential oils in cancer and highlights some promising future directions. It integrates chemistry, pharmacology, and medicine while discussing bioactive essential oils in experimental models and clinical studies of cancer. The book is a valuable resource for all engaged in the study of natural products and their synthetic derivatives, particularly for those interested in academic research and pharmaceutical and food industries dedicated in the discovery of useful agents for the therapy or prevention of cancer.

From humble beginnings over 25 years ago as a lipid kinase activity associated with certain oncoproteins, PI3K (phosphoinositide 3-kinase) has been catapulted to the forefront of drug development in cancer, immunity and thrombosis, with the first clinical trials of PI3K pathway inhibitors now in progress. Here we give a brief overview of some key discoveries in the PI3K area and their impact, and include thoughts on the current state of the field, and where it could go from here

This volume gathers the leading research on antibody-drug conjugates and immunotoxins. Following a rigorous overview, the volume delves into focused sections on all aspects of ADCs and ITs from clinical development through to targeted therapeutic applications and the latest technologies.

Patients with advanced breast or prostate cancers usually develop bone metastases. The principal complications resulting from metastatic bone disease are pain, spinal cord compression, pathologic fractures and bone marrow suppression. Improving the management of bone metastases is crucial to quality of life for patients with breast and prostate cancer.

Advances in understanding of the molecular mechanisms underlying the pathophysiology of bone metastasis are driving the development of new therapeutic strategies.

Over the years of cancer investigation a lot of discoveries in this field were made, and many associations between various biological carcinogens and cancer were revealed. Some of them are credibly determined, thus these infectious agents (human papilloma virus, hepatitis B virus, hepatitis C virus, Epstein-Barr virus, human herpes virus 8, human T-cell lymphotropic virus 1, human immunodeficiency virus, Merkel cell polyomavirus, Helicobacter pylori, Opisthorchis viverrini, Clonorchis sinensis, Schistosoma haematobium) are recognized as carcinogens and probable carcinogens by International Agency for Research on Cancer (IARC). The problem is of large importance, since share of infectious agents-related cancer cases is steadily increasing, reaching 25% according to certain estimates. It is worth noting that many of cancer cases are caused by infectious agents other than -conventional ones- like HPV, EBV, HBV, HCV, H.pylori etc. In recent years, a number of significant breakthroughs in the field were performed, such as the discovery of the microbiota role in cancer causation."

During the last 20 years it has become increasingly clear that the tumor micro-environment, the tumor stroma with its cellular end extracellular components, plays an crucial role in regulating tumor growth and progression. This book on "Tumor-associated fibroblasts and their matrix" as part of the series on "Tumor-Microenvironment" is the first comprehensive discussion of these two main players of the tumor microenvironment. The best experts in this new area of tumor research and therapy review the role of these major components in the tumor stroma in the process of tumor development and progression. They discuss their interaction with other players such as blood vessels and immune cells, and show novel perspectives for tumor therapy. This compilation of excellent contributions of the best known experts in this important field in cancer research and therapy is a must for all scientists engaged in basic and clinical research. Increasing evidence of successful targeting of both cellular and matrix components in tumor therapy renders this book of particular interest for scientists engaged in pharmaceutical industry searching for new components for cancer therapy.