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.

Clinics in Developmental Medicine No.166

Ranging from epidemiology and neuroimaging through the general principles of surgery and radiotherapy/chemotherapy to issues of palliative care and quality of life, this concise, broad-ranging and practical text covers all clinical aspects of central nervous system tumours in children. It provides an overview of current important issues in diagnosis and management, and focuses on important areas of research, with an emphasis on the areas likely to impact on clinical practice. It will be essential reading for paediatric oncologists, medical and clinical oncologists, neurosurgeons, and paediatricians involved in the care of children with brain tumours, trainees in these and related specialties, specialist nurses and paramedical staff.

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.

It has become clear that tumors result from excessive cell proliferation and a corresponding reduction in cell death caused by the successive accumulation of mutations in key regulatory target genes over time. During the 1980s, a number of oncogenes were characterized, whereas from the 1990s to the present, the emp- sis has shifted to tumor suppressor genes (TSGs). It has become clear that oncogenes and TSGs function in the same pathways, providing positive and negative growth regulatory activities. The signaling pathways controlled by these genes involve virtually every process in cell biology, including nuclear events, cell cycle, cell death, cytoskeletal, cell membrane, angiogenesis, and cell adhesion effects. Mu- tions in tumor suppressor genes have been identified in familial cancer syndromes, and the same genes in many cases have been found to be mutationally inactivated in sporadically occurring cancers. In their normal state, TSGs control cancer development and progression, as well as contribute to the sensitivity of cancers to a variety of therapeutics. Understanding the classes of TSGs, the biochemical pa- ways they function in, and how they are regulated provides an essential lesson in cancer biology. We cannot hope to advance our current knowledge and to develop new and more effective therapies without understanding the relevant pathways and how they influence the present approaches to therapy. Moreover, it is important to be able to access not only the powerful tools now available to discover these genes, but also their links to cell biology and growth control.

Genetic susceptibility refers to how variations in a person 's genes increase or decrease his or her susceptibility to environmental factors, such as chemicals, radiation and lifestyle (diet and smoking). This volume will explore the latest findings in the area of genetic susceptibility to gastrointestinal cancers, focusing on molecular epidemiology, DNA repair, and gene-environment interactions to identify factors that affect the incidence of GI cancers. Topics will include germline susceptibility, including Mendelian patterns of inheritance and gene-environment interactions that lead to cancer etiology.

Oncological imaging has thoroughly changed in the past decade, especially due to the introduction of PET and 18FDG. In "Positron Emission Tomography," expert referring specialists and professional imagers seek to help bridge some of the knowledge gaps in several oncological domains. The book s goal is to aid in the improvement of communicative competences: to communicate scan findings so that the referring specialist receives proper advice from the imager, and that, alternatively, the referring one provides the imager with appropriate clinical details to allow for a proper interpretation, and that the referring specialist is aware of the possibilities and limitations of the requested technology. While it focuses on FDG PET, other radiopharmaceuticals are covered as well, where appropriate. Written for the highly respected "Methods in Molecular Biology " series, this volume provides the kind of detailed description and implementation advice that is crucial for getting optimal results.

Authoritative and convenient, "Positron Emission Tomography" serves as an excellent reference for oncologists, surgeons, radiotherapists, radiologists, nuclear medicine physicians, and pathologists desiring a stronger synergy within their vital efforts."

This timely revision of the authoritative handbook gives a wide range of providers practical insights and strategies for treating cancer survivors' long-term physical and mental health issues. Details of new and emerging trends in research and practice enhance readers' awareness of cancer survivor problems so they may better detect, monitor, intervene in, and if possible prevent disturbing conditions and potentially harmful outcomes. Of particular emphasis in this model of care are recognizing each patient's uniqueness within the survivor population and being a co-pilot as survivors navigate their self-management. New or updated chapters cover major challenges to survivors' quality of life and options for service delivery across key life domains, including: Adaptation and coping post-treatment. Problems of aging in survivorship, disparities and financial hardship. Well-being concerns including physical activity, weight loss, nutrition, and smoking cessation. Core functional areas such as work, sleep, relationships, and cognition. Large-scale symptoms including pain, distress, and fatigue. Models of care including primary care and comprehensive cancer center. International perspectives PLUS, insights about lessons learned and challenges ahead. With survivorship and its care becoming an ever more important part of the clinical landscape, the Second Edition of the Handbook of Cancer Survivorship is an essential reference for oncologists, rehabilitation professionals, public health, health promotion and disease prevention specialists, and epidemiologists.

¿Drs. Franco and Rohan bring together a timely and comprehensive set of reviews describing the biologic basis of carcinogenesis, issues related to measurement and interpretation of cancer precursors, site specific precancerous conditions, and control of cancer precursors ¿The book has several important strengths, most notably the wealth of current information on cancer precursors and related topics provided by an impressive cast of cancer researchers. ¿ it effectively provides specific and compelling reasons for studying cancer precursors, the most up-to-date and comprehensive collection of reviews on the topic, and a realistic picture of the complexities facing research of cancer precursors.¿ ¿American Journal of Epidemiology "In this book, Drs. Franco and Rohan have succeeded in preparing a comprehensive, timely, and critical review of the substantial progress that has been made in our understanding of cancer precursors. They have enlisted experts in the field who have contributed authoritative chapters to a wide variety of cancers with emphasis on the etiology and natural history, including the role of environmental and heritable factor that provoke normal cells to undergo malignant transformation. Epidemiologic data are linked whenever possible to molecular as well as clasical cellular pathology, providing a fuller understanding of the casual events and mechanisms that initiate the carcinogenic process." -From the Foreward by Joseph F. Fraumeni, Jr., M.D., M.S. Director, Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville, MD This book provides an overview of the progress made in the last few years on the epidemiology, detection methods, and preventive stategies for cancer precursors. Contributors to the 25 chapters are among the world's most knowledgeable scientists in the areas of molecular pathology, epidemiology, and control of cancer precursors. Their reviews of the topic are accessible to a large professional base that includes basic cancer researchers, clinical oncologists, pathologists, molecular biologists, epidemiologists, nurses, health professionals working on policy implications, and graduate students in cancer-related fields. Divided into five sections, the book begins with brief overviews of the molecular basis of carcinogenesis and of the histological aspects of cancer precursors. Issues related to the measurement, interpretation, and the study of precursor lesions are addressed in Part II, including timely chapters on epidemiologic approaches to studying intermediate endpoints, the impact of measurement error, and methods of processing biological specimens for molecular epidemiology studies. The main section of the text is found in Part III, with chapters on cancer precursors at the most important anatomical sites at which solid tumors occur, including the lung, breast, colon, esophagus, and prostate. The site-specific reviews include discussions of the epidemiology of those lesions, and, where appropriate, aspects of their detection and prevention. The final sections of the book feature valuable overviews on screening and prevention strategies and the role of evidence-based medicine in judging the value of such strategies for national and international policy guidelines on cancer control.

The majority of cancers present at a relatively advanced stage in which invasion within the primary organ is well established and metastases to lymph and distant organs are either clinically apparent or present at the microscopic level. However, it is increasingly recognized that the natural history of cancer formation is a long and complex path taking many years to develop to a clinically apparent stage in most cases. Furthermore, for most solid tumours there is a pre-invasive or intraepithelial stage of disease. This affords the opportunity for early detection and prevention of invasive disease and hence a cure. However, with this advancing knowledge comes a whole plethora of questions which will be explored in this monograph. Firstly, we need to understand the global burden of pre-invasive disease and what the public health implications might be for wide-scale screening programmes. In the western world we already have experience of screening for cervical, breast, prostate and more recently colon cancer. As well as their potential benefits these programmes have financial and psychosocial implications which need to be carefully weighed. This is especially true since many pre-invasive lesions will not progress to cancer in a individual's lifetime. In addition, there are questions concerning whether screening reduces the cancer burden or in fact distorts the survival figures through lead-time bias. Secondly, at the level of epidemiology and molecular pathogenesis there are important questions regarding the aetiology of pre-invasive lesions; an understanding of which might lead to possible chemopreventive strategies. For example, it would be helpful to know the extent to which the likelihood of developing a pre-invasive lesion is influenced by lifestyle or genetic factors and how these factors influence the risk of progression to invasive disease. At the molecular level we need to understand the pathways and molecular mechanisms, both genetic and epigenetic, by which cells achieve the capacity to invade. Thirdly, in order make clinical progress we need biomarkers to identify and risk stratify individuals with pre-invasive lesions. These biomarkers might be applied to the serum as in Prostate Specific Antigen in prostate cancer or be applied to tissue samples, such as oestrogen receptor status in breast cancer. In order to utilize biomarkers in the context of a screening programme there are issue around the invasiveness of the test as well as its positive and negative predictive value. With advances in molecular imaging there is now the exciting possibility of incorporating a molecular tag to a non-invasive imaging modality. Fourthly, in order to justify screening early detection must be coupled to a treatment strategy. If the chemopreventive agent is very well tolerated, then as well as targeting high risk groups, one might consider treatment at the population level. Aspirin is one such drug which has been extensively assessed in the context of colon cancer chemoprevention trials. Trials of aspirin chemoprevention are now being applied to other cancers such as oesophageal adenocarcinoma and since many individuals take aspirin for .chemoprevention of cardiovascular disease the cancer incidence can be ascertained in these populations. In order to understand the more general issues raised from the discussions above it is useful to consider disease specific examples. Our understanding of pre-invasive disease varies according to the organ site and there are lessons to be learned from these experiences. For example, there is now the prospect of a vaccine for cervical cancer with important questions about how this might be applied to the high incidence areas of the developing world. On the other hand, ductal carcinoma in situ is currently treated by mastectomy which is more radical than the treatment received by many women with invasive disease. Oesophageal adenocarcinoma, which is my own area of expertise is interesting because of the rapid rise in incidence in the western world and the clinically accessible pre-invasive lesion called Barrett's oesophagus. However, most cases of Barrett's oesophagus remain undiagnosed and it is not yet clear how to effectively diagnose, monitor and treat this condition without recourse to mass endoscopy with substantial cost implications. In conclusion, in an era in which preventive medicine is a major concern for consumers, health-policy makers and politicians pre-invasive disease is likely to become a major part of cancer medicine.

One of the most important developments in the field of cardiovascular medicine over the last two decades has been recognition of the key role played by arterial thrombosis in the pathogenesis of acute coronary syndromes, ischemic complications of percutane- ous coronary revascularization, and coronary and peripheral atherosclerosis. The phar- macologic armamentarium directed against vascular thrombosis has thus expanded substantially during that time, with development of new fibrinolytic agents, low-molecu- lar-weight heparins, direct thrombin inhibitors, antagonists to platelet activation, and the platelet glycoprotein lIb/IlIa inhibitors. Though clinical investigations of these com- pounds have been marked by failures as well as successes, there is little doubt that enhanced antithrombotic therapies have markedly improved the outcome of patients undergoing coronary revascularization or with acute coronary syndromes. Glycoprotein IIblIlIa receptor antagonists were introduced into clinical practice to overcome the limitations of approaches that inhibit only individual pathways of platelet activation. Multiple mechanisms of platelet activation in response to different agonists converge on the platelet membrane glycoprotein IIblIlIa complex, the "final common pathway" of platelet aggregation. The clinical hemorrhagic syndrome caused by a rare inherited defect in this receptor (Glanzmann' s thrombasthenia), characterized by muco- cutaneous and postsurgical bleeding, but infrequent spontaneous organ (particularly central nervous system) bleeding, suggested that therapeutic inhibition of this receptor might be a potent, yet well-tolerated means of treating thrombotic disorders.

Leading investigators and clinicians detail the different mechanisms used by tumors to escape and impair the immune system and then spell out possible clinical strategies to prevent or reverse tumor-induced immune dysfunction. The authors review the mechanisms of immune dysfunction and evasion mechanisms in histologically diverse human tumors, focusing on tumor-induced molecular defects in T cells and antigen-presenting cells (dendritic cells and tumors), that may serve as biomarkers for patient prognosis. They discuss the means by which these immune functions may be protected or restored in order to more effectively support the process of tumor rejection in situ. Cutting-edge techniques are outlined with the capacity to monitor the strength and quality of patients' immune responses using immunocytometry, MHC-peptide tetramers combined with apoptosis assay, ELISPOT assay, and detection of MHC-TAA peptide complexes on tumor cells.

The possibility of treating cancer, a disease frequently defined by
genetic defects, by introducing genes that target these very
alterations has generated tremendous enthusiasm. This enthusiasm,
however, has been tempered by an increasing number of obstacles to
successful therapy, including vector systems that do not reach systemic
metastases, therapeutic genes with redundant mechanisms allowing for
cellular resistance, and toxicities in clinical trials that result in
premature closure. The three comprehensive sections of this volume
present currently available cancer gene therapy techniques, with
specific attention to these trouble spots. Part I describes the various
aspects of gene delivery including vehicles, or vectors, and their
respective characteristics and production methods. In Part II, the
contributors discuss strategies and targets for the treatment of
cancer, including methods for cell-death therapies, correction of
underlying genetic defects at the molecular level, and activation of
the immune system or tumor microenvironment. The contributors provide a
succinct framework for understanding the basic underlying oncogenic
changes, which encourages the development of vectors engineered to
exploit these gene mutations through selective spread of the vector in
tumor cells with the specific changes. Finally, in Part III, experts in
clinical gene therapy trials discuss the difficulties inherent in
bringing gene therapy treatment for cancer to the clinic, and principal
investigators present gene therapy approaches in the clinical testing
stage and the results that have reached the stage ofclinical
testing.of these trials.

This work presents the most advanced discoveries from translational research laboratories directly involved in identifying molecules and signalling pathways that play an instrumental role in metastasis. In contrast to other works, conventionally focused on a single type of tumour, the various chapters in this book provide a broad perspective of the similarities and discrepancies among the dissemination of several solid malignancies. Through recurrent and overlapping references to molecular mechanisms and mediators, the readers will gain knowledge of the common ground in metastasis from a single source. Finally, an introductory chapter provides a clinical perspective of the problems presented by metastatic tumours for diagnosis and treatment. The work presented here is directed to researchers in tumour biology with a developing interest in metastatic dissemination as well as medical and graduate students seeking to expand and integrate the notions acquired in basic cancer biology and oncology courses.

With the coming of the new millennium we are witnessing a revolution in our understanding of cancer genetics. These are very exciting times. Today we have at our disposal the technology to diagnose abnormalities in our cancer genes and the means to correct the deficit and very soon we will have the complete sequence of the human genome. With the use of gene chip technology the way doctors will be able to assess patients will change completely. Today we can diagnose abnormalities in ten thousand genes and within a short period of time we will be able to screen through our genome and discover potential abnormalities in our proto-oncogenes, tumour suppressor genes, differentiating genes, apoptotic genes and pro-inflammatory genes. In this book various authors have highlighted specific genes that could be expressed, overexpressed, neutralised or h- nessed to achieve cancer control. The problem of transferring the therapeutic gene into the cancer cell has been partly addressed with major developments in the field of naked plasmid DNA, adenovirus, retrovirus and adeno-associated viruses. However, further improvements are yet to be made to achieve significant gene transfer. Gene expression, in particular specificity of gene transfer, is obviously an important issue and one which is highlighted in this book by the use of specific promoter.

This book is a simple guide to the diagnosis, investigation, and treatment of all gynaecological cancers. It discusses the management of patients with gynaecological malignancies; considers the principles of chemotherapy, radiotherapy, and surgery; explains when and why each modality is used in treatment; covers the pathology of gynaecological cancer; discusses treatment of the advanced disease; and includes a chapter on the role of palliative care. The multidisciplinary approach reflects the cooperative practice in combined clinics.

Antifolates are an important class of anticancer drugs originally developed as anti leu- kemic agents, but now used, usually in combination with other drugs, for the treatment of a wide range of tumors, notably carcinomas of the head and neck, breast, germ cell tumors, non-Hodgkin's lymphoma, acute lymphoblastic leukemia, and osteogenic sar- comas. 5-Fluorouracil and its prodrugs also target, in part, the folate-dependent enzyme, thymidylate synthase. Furthermore, folate supplementation in the form of leucovorin, modulates 5-fluororuacil activity. 5-Fluorouracil is widely used in the treatment of colorectal and gastric cancer and in combination for other solid tumors such as breast and head and neck cancers. Ongoing clinical trials with the newer antifolates suggest that the range of solid tumors where these agents will be of use may broaden further. Half a century ago, interesting scientific and clinical discoveries suggested that folie acid was a vitamin involved in vital cellular metabolic processes. The folate analogs, aminopterin and methotrexate, were synthesized by the American Cyanamid Company in an attempt to interfere with these processes and were shown to have anticancer activity by Farber and his colleagues. Hence, the principle of antimetabolite therapy for the treatment of cancer was established. Biomedical research over the following years led to a deeper understanding of the complex biochemical pharmacology of folates and antifolates. Selective antimicrobial agents were discovered, but more tumor-selective anticancer agents did not immediately emerge.

This volume provides a biological and pharmacological background for regional cancer therapy, strategies and techniques for regional therapies, and specific indications and results for different tumor entities. Clinical trial concepts and detailed treatment protocols are also presented. This book is essential reading for researchers and clinicians engaged in seeking advanced therapeutic options for cancer patients worldwide.

This volume, Biological and Hormonal Therapies of Cancer, which is part of the series Cancer Treatment and Research, presents selected new information concerning biologic and hormonal therapy of cancer. We have attempted to provide the reader with topics of major interest in a timely fashion. There is renewed interest in biologic therapy of cancer. Two chapters review the role of interferon in the hematologic malignancies and in solid tumors. Vaccine therapies have come to the forefront of cancer therapy re cently, and two chapters approach different strategies of vaccine therapies; one reviews the cellular vaccine therapies and another the anti-idiotype ap proach. The hormonal therapy chapters focus on current uses of endocrine therapy in endometrial, breast, and prostate cancer. In addition, hormonal strategies for the prevention of breast cancer and endometrial cancer, including excit ing information relating to phytochemicals, are presented. The effects of tamoxifen on endometrium is a topic of major interest and is discussed in detail. Finally, there is a chapter on estrogen receptor expression and regula tion in human breast cancer. These chapters are all written by experts in the field and contain timely and relevant information of interest to laboratory and clinical scientists and practitioners alike. Biologic and endocrine therapies represent major areas of cancer research interest. The advent of newer biologic therapies, including new antibody targeted treatments, and the use of biologics as tumor modulators to enhance the effects of other treatment regimens is an exploding avenue of research."