Much work over the last two decades has firmly established that loss of cell cycle checkpoint regulation, and resultant unabated cellular proliferation, is an inherent characteristic of cancer. This loss may occur through aberration in any single component involved in signal transduction pathways that orchestrate checkpoint regulation, which may manifest through either a failure to activate the checkpoint or a failure to respond to the activated checkpoint. In normal cells, checkpoint pathways are activated when genetic or cellular homeostasis is compromised, and signals are then transduced to re-stabilize homeostasis, and, failing this, to activate the apoptotic machinery to induce a cellular suicidal response. This implies that both survival and cell death pathways are induced following checkpoint activation, and that the final decision is dependant on the net result of integrating the two sets of signals.

It is intriguing that checkpoint pathways are also critical in cancer therapy to provide an apoptotic stimulus when cellular damage induced by the therapeutic agent is detected by the sensor system. Therefore, it is not surprising that failure in pro-survival checkpoint response will render tumor cells hypersensitive to cytotoxics and, conversely, failure in pro-apoptotic checkpoint response will induce genetic instability and/or therapeutic resistance. Understanding the intricacies of checkpoint response is, therefore, central to the design of therapeutic regimen that will enhance antitumor effects. Although early versions of this design entail combination of cytotoxic agents with cell cycle or checkpoint inhibitors, a greater understanding of the concepts could make such combinations clinically more effective. The contributions in this book will consolidate the current state of knowledge on checkpoint responses that may lay the foundation for hypothesis-driven rational approaches in advancing the management of cancer.

The immediate attraction of the book to the scientific community is that it represents a timely opportunity to build upon existing concepts of checkpoints to expand our understanding of the inner workings of the critical checkpoint machinery. The present understanding has provided ample appreciation that response to checkpoint activation is manifested through coordinated inhibition of cyclin-dependent kinase (CDK) complexes in G1, S and/or the G2 phase in order to arrest the cell cycle. Kinase inhibition can occur through several mechanisms, including inhibitory phosphorylation of CDK, destruction of the cognate cyclins, and recruitment of CDK inhibitors from the INK and WAF1/CIP1 families. However, the wealth of information from recent discoveries needs to be examined critically to consolidate our conceptual knowledge of checkpoints. At the same time, there is acute awareness in the diversity of checkpoint response between cytotoxic agents, and this serves as a reminder of the magnitude of complexity that is inherent in checkpoint regulation. This volume is intended to bring the cancer research community closer toward an improved understanding of this regulation, how checkpoint abnormalities can impact negatively on cancer therapy, and emerging strategies to target checkpoint response as a therapeutic end-point.

At the time of the first edition of Principles of Cancer Biotherapy in 1987, this book represented the first comprehensive textbook on biological therapy. In 1991, when the second edition was published, there was still some doubt on the part of many oncologists and cancer researchers as to the therapeutic value of these new approaches. By 2003 and the fourth edition, it was generally agreed that biopharmaceuticals were producing major opportunities for new cancer therapies. Cancer biotherapy has now truly matured into the fourth modality of cancer treatment. This fifth revised edition describes the tremendous progress that has been made in recent years using biologicals in cancer treatment.

This book summarizes an evolving science and a rapidly changing medical practice in biotherapy. In this new millennium, it is now possible to envision a much more diversified system of cancer research and treatment that will afford greater opportunities for a patient s personalized cancer treatment. This was first envisioned in the 1987 initial edition of this textbook and is now a new and popular approach to cancer treatment. Some forms of cancer biotherapy use the strategy of tumor stabilization and control through continued biological therapy, akin to the use of insulin in the treatment of diabetes.

This textbook illustrates new methods of thinking and new strategies for control of cancer. It is always difficult to move from past dogma to future opportunity, but this fifth edition of Principles of Cancer Biotherapy illustrates why it is so important to the patients for researchers and clinicians to explore and quickly apply these new opportunities in cancer biotherapy."

This book provides a comprehensive overview of the latest research on the molecular players in the tumor microenvironment, including MicroRNAs, estrogen, Caveolin-1, Nitric Oxide, RANK/RANKL signaling, , COX-2 Signaling, Renin-angiotensin system, and more. Taken alongside its companion volumes, Tumor Microenvironment: Molecular Players - Part B updates us on what we know about the tumor microenvironment, as well as future directions. This book is essential reading for advanced cell biology and cancer biology students as well as researchers seeking an update on research in the tumor microenvironment.

This volume will be the first to provide a comprehensive description of tumor dormancy. It will define the clinical and biological aspects of this phenomenon, as well as the cellular and molecular mechanisms associated with tumor dormancy. Chapters will be authored by world-renewed experts who are conducting cutting-edge research in the field. A unique feature will be a conclusive paragraph detailing future development and foreseeable clinical applications at the end of each chapter. The volume will serve as a fundamental instrument for every researcher and clinician interested in the field of tumor dormancy as well as a means of disseminating stimulating concepts and prompting the development of innovative technological solutions.

In 2000 the Department of Health issued a number of initiatives, with improving cancer treatment and research, and providing greater resources for cancer care being made a priority. Nurses and their colleague will be at the forefront of these changes. The book presents specialised biological information on what cancer is, how it damages the body, and how cancer treatments work. Engaging, accessible and illustrated throughout, this unique text: -explains the basic biology of cancer -discusses the biology of wide range of common cancers -identifies and explains the biological causes of cancer -explains drug action in chemotherapy and analgesia -explains the link between diet and cancer, and how diet is important in cancer therapy -discusses the biological basis of a range of nursing skills linked to cancer. This book will provide nurses with the essential knowledge required for working with cancer patient and their families, and will enable them to work with current and new forms of cancer treatment. It will also be of great use to clinical staff and nurse educators.

Progress in the treatment of cancer over the past two decades has been rapid with many new and novel therapeutic modalities arriving at an unprecedented pace. Overall cancer mortality rates have actually begun to fall in parallel with progress in the diagnosis and treatment of malignant disease. Despite our advances in the understanding of the biology and molecular genetics of cancer, as well as the availability of an increasing array of effective therapies, cancer treatment today and for the foreseeable future will include the traditional modalities of surgery, radiation therapy and chemotherapy. Myelosuppressive agents with their potential hematopoietic toxicities remain the mainstay of systemic treatment for both metastatic and early stage cancer. The complications of cancer chemotherapy have serious impact on a patient's well being and overall quality of life. Fortunately, advances in cancer treatment have been accompanied by equally impressive progress in the availability of a wide array of supportive care modalities which have greatly enhanced the ability of oncologists to minimize the impact of cancer and its treatment on patient quality of life as well improve delivery of potentially curative cancer treatment. Despite the increasing complexity of modern cancer treatment, it is the obligation of the oncologist as well as the entire cancer care team to be certain that cancer patients receive the optimal supportive care available for their disease and its treatment. Among the most serious and potentially life threatening toxicities of cancer treatment are the hematologic toxicities accompanying myelosuppression including anemia and associated asthenia and fatigue, neutropenia and fever associated with infection in the immunocompromised patient and thrombocytopenia and accompanying risk of bleeding. Special supportive care needs arise in the very elderly care patient that may tax the ability of even the most skilled clinician. Despite the considerable progress that has been made with more effective and safer treatment strategies, myelosuppressive chemotherapy will remain the mainstay of systemic treatment for cancer for the foreseeable future. While considerable progress has occurred, better methods and broader application of supportive care measures are needed to reduce the symptomatic effects of cancer and the associated toxicities associated with cancer treatment. No area of cancer supportive care better illustrates the progress that has resulted from advances in our understanding of cellular and molecular biology, genetic engineering and the development of more effective yet often more toxic cancer treatments than that of the hematopoietic growth factors. This volume will review and integrate the major advances in our understanding of the underlying molecular biology and pharmacology of these agents along with the results of well designed and executed randomized controlled trials of the erythroid stimulating agents, the myeloid growth factors and the new thrombopoietic agents each addressing a major threat associated with bone marrow suppression accompanying cancer treatment. The current clinical utilization of these agents is based on numerous randomized controlled trials and meta-analyses along with evidence-based clinical practice guidelines developed by professional societies guiding their appropriate and cost-effective use in clinical care.

A comprehensive review of the recent developments in DNA repair that have potential for translational and clinical applications. The authors explain in detail the various mechanisms by which cancer cells can circumvent anticancer therapy and limits its usefulness in patients. They also review the clinical impact of such novel inhibitors of DNA repair mechanisms as methylguanine-DNA-methyltransferase. Also examined are inhibitors of other DNA repair enzymes such as PARP and DNA-PK, now under development and close to clinical trials. The book captures-for both cancer researchers and practicing oncologists dealing with hallmark "relapse" or "drug resistance" phenomena on a daily basis-the many exciting new uses of DNA repair inhibitors, either alone or in combination with anticancer therapies.

This volume, in discussing resistance to ibritumomab, will focus on the mechanism, hematological aspects, radiological and nuclear medicine aspects, and medical physics that deal with radiation dosimetry, and will outline future prospects for overcoming resistance and enhancing efficacy of ibritumomab.

This volume will explore the latest findings in research into the genetics of breast and reproductive cancers, covering the epidemiological aspects of these cancers, their etiology, the effect of environment on genes and cancer etiology, and how research in this area can lead to development of preventative measures and treatments.

Presenting contributions by 66 experts representing 13 countries, Volume 10 of the series Stem Cells and Cancer Stem Cells synthesizes current understanding of the causes, diagnosis, and therapy of major human diseases and debilitating tissue and organ injuries, using cell-based treatment. This volume presents contemporary research into generation, preservation, and uses of stem cells in fighting disease and tissue/organ injuries.

The contents of the volume are organized into five sections. Mesenchymal Stem Cells section includes chapters on the use of stem cells in bone regeneration, studies and trials of stem cells in autoimmune diseases, and differences between adipose tissue-derived mesenchymal stem cells and bone marrow-derived mesenchymal stem cells as regulators of immune response. Induced Pluripotent Stem Cells section offers chapters on drug discovery using human IPSC-based disease models, and on generation of antigen-specific lymphocytes from IPSCs. Neural Cells and Neural Stem Cells section discusses use of bacterial artificial chromosomes in the genetic identification of stem cell-derived neural cell types, and use of moderate low temperature to preserve the stemness of neural stem cells. The section, Role of Stem Cells in Disease, discusses stem cell support in high-dose chemotherapy of Non-Hodgkin s Lymphomas; potential targets for drug resistant leukemic stem cells, bone marrow stem cell therapies for diabetes mellitus. This section also discusses the use of stem cells in treating thyroid, breast and bone cancers, hempophilia and Parkinson s Disease. The section, Stem Cell Transplantation, includes chapters on reducing fungal infection in allogenic stem cell transplantation patients, use of Bulsufan/Fludarabine for conditioning in haematopoietic stem cell transplantation, and interleukin-7 receptor alpha polymorphisms in allogeneic stem cell transplantation.

The editor, M.A. Hayat, is a Distinguished Professor in the Department of Biological, Sciences at Kean University, Union, New Jersey, USA.

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The gastrointestinal track provides one of the distinct systems where multiple malignancies, including adenocarcinoma of the pancreas, esophagus and colon are each associated with obesity. This unique association is covered in this volume of Energy Balance and Cancer from the epidemiologic, biologic and potential etiologic viewpoint. The focus on possible dietary contribution as well as the role of exercise in prevention and therapy is presented in both animal model and patient based studies. Special focus is provided also on the role of genetic mutations and inflammatory pathways as drivers of these obesity related gastrointestinal malignancies. Overall, this volume on Energy Balance and Gastrointestinal Malignancies should be valuable to Epidemiologists, Gastroenterologists and Oncologists, as well as to students and researchers from multiple disciplines interested in understanding and disrupting the association between obesity and cancer.

In this book, clinicians and basic scientists from USA, India, and other countries discuss the rationales and clinical experiences with targeted approaches to treat, prevent, or manage cancer. Cancer is a hyperproliferative disorder that is regulated by multiple genes and multiple cell signaling pathways. Genomics, proteomics, and metabolomics have revealed that dysregulation of dozens of genes and their products occur in any given cell type that ultimately leads to cancer. These discoveries are providing unprecedented opportunities to tackle cancer by multi-faceted approaches that target these underpinnings. This book emphasizes a multi-targeted approach to treating cancer, the focus of the 5th International Conference on Translational Cancer Research that was held in Vigyan Bhawan, Delhi (India) from Feb 6-9, 2014.

Despite tremendous recent advances in the treatment of most malignancies, there remain several critical questions for each cancer. This particularly true for the surgical management of solid-organ malignancies. Comparative effectiveness is a relatively new term which encompasses the age-old concepts of how best to treat cancer patients. Comparative effectiveness is defined as the direct comparison of healthcare interventions to determine which work best for which patients when considering the benefits and risks. The Institute of Medicine has defined comparative effectiveness research(CER) as the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care. CER is certainly best done with well-conducted randomized controlled trials. Unfortunately, clinical trials are not always feasible owing to the impracticality of conducting the trial, the considerable cost, and the time required to complete the trial. These challenges are even more pronounced with respect to surgical treatment. Thus alternative approaches may need to be considered in order to address pressing questions in the care of the oncology patient. These approaches may include well-conducted retrospective cohort studies from cancer registries and other data sources, decision and cost-effectiveness analyses, and other novel methodologies. This book lays out the current critical questions for each major malignancy and proposes approaches to gain answers to these pressing questions.

Mast cells are versatile, tissue-homing secretory cells, which were first described by Paul Ehrlich in 1878. Mast cells have long been implicated in the pathogenesis of allergic reactions and certain protective responses to parasites. Their functional role, however, has been discovered to be increasingly complex and multifarious. Mast cells have been implicated in various cell-mediated immune reactions, being found in tissues from multiple disease sites, and as a component of the host reaction to bacteria, parasite, and even virus infections. They have also been shown to participate to angiogenic and tissue repair processes after injury. The importance of a possible functional link between chronic inflammation and cancer has long been recognized. As most tumours contain inflammatory cell infiltrates, which often include plentiful mast cells, the question as to the possible contribution of mast cells to tumour development has progressively been emerged. In this book, the general biology of these cells, their development, anatomical distribution and phenotype as well as their secretory products will first be discussed. The biology of tumour cells, their structural and molecular characteristics, the specificity of the tumour microenvironment and the development of a vascular network in the tumour context will be analyzed. The involvement of mast cells in tumour biology and tumour fate will then be considered, with particular emphasis on the capacity of these cells to stimulate tumour growth by promoting angiogenesis and lymphangiogenesis. The last chapter suggest that mast cells may serve as a novel therapeutic target for cancer treatment.

This volume describes up-to-date techniques used in understanding the molecular biology of acute myeloid leukemia (AML) and addressing advances in diagnosis, classification, prognostication, and therapeutic strategies to potentially impact overall patient survival. The chapters in this book cover topics such as: cytochemical staining, single-cell mass cytometry of AML and Leukemia stem/progenitor cells, microsphere-based assessment of DNA methylation for AML prognosis, a zebrafish model for evaluating the function of human leukemic gene IDH1 and its mutation, and the isolation of biologically active exosomes from plasma of patients with cancer. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and practical, Acute Myeloid Leukemia: Methods and Protocols is a valuable resource for scientists and researchers to further their studies and advancements in the field of AML.

The increase in new medical technology and experimental treatments has made the study of medical ethics essential for practitioners on all levels. This book brings together experts in the fields of pediatric hemotology/oncology, ethics, and law to examine legal and ethical issues surrounding the treatment of children with cancer or blood disease. The contributors present thoughtful discussions of ethical considerations of such practices as bone marrow transplantation, caring for hemophiliacs, preventing sickle cell disease, informing patients of treatment side effects, the statistical design of clinical trials, and the activities of the Institutional Review Board.

A collection of both well-established and cutting-edge methods for investigating breast cancer biology not only in the laboratory, but also in clinical settings. These readily reproducible techniques solve a variety of problems, ranging from how to collect, store, and prepare human breast tumor samples for analysis, to analyzing cells in vivo and in vitro. Additional chapters address the technology of handling biopsies, new methods for analyzing genes and gene expression, markers of clinical outcome and progress, analysis of tumor-derived proteins and antigens, validating targets, and investigating the biology of newly discovered genes.

This volume provides a comprehensive treatise on the latest studies linking prostate cancer with energy balance, which together constitute a major challenge and opportunity for research scientists and clinicians especially those dealing with the expanding population of older men confronted with obesity and associated comorbidities. This volume should be a valuable resource to physicians, oncologists, urologists, endocrinologists, nurses, nutritionists, dieticians, and exercise therapists dealing with men with energy balance issues and/or questions regarding the linkage between energy balance and cancer. Moreover, this volume should serve as an important resource for cancer researchers especially for scientists studying lifestyle modification and prevention strategies to better understand and disrupt the linkage between obesity and cancer.

Recent studies have shown that cells from adipose tissue are capable of trafficking to tumors, thus enabling paracrine action of adipokines from within the tumor microenvironment. Increased tumor vascularization, immune system suppression and direct effects on malignant cell survival and proliferation have been investigated as mechanisms regulated by adipokines. The goal of this book is to discuss data pointing to the role of adipose tissue in cancer and to dissect individual mechanisms through which adipose tissue excess or restriction could influence cancer progression.

As cells mature they naturally stop dividing and enter a period called senescence. But cellular senescence can also be induced prematurely by certain oncogenes involved in cancer development. Cellular senescence, a growth-arrest program that limits the lifespan of mammalian cells and prevents unlimited cell proliferation, is attracting considerable interest because of its links to tumor suppression.

The study of viruses necessarily involves dissecting the intimate details of cellular pathways. Viruses have often been employed as tools in studying cellular pathways, as was done by early retrovirologists such as Peyton Rous in attempting to understand the mechanism of cellular transformation and oncogenesis. On the other side of the coin, virologists seek to de?ne those cellular elements interacting intimatelywiththeir virus ofinterestinorder to better understand viral replication itself, and in some cases to develop antiviral strategies. It is in the intersection of virology and cell biology that many of us ?nd the most rewarding aspects of our research. When a new discovery yields insights into basic cellular mechanisms and presents new targets for int- vention to ?ght a serious pathogen, the impact can be high and the excitement intense. HIV has been no exception to the rule that viruses reveal many basic aspects of cellular biology. In recent years, in part because of the importance of HIV as a major cause of human suffering, numerous cellular processes have been elucidated through work on processes or proteins of this human retrovirus. The excitement in this ?eld is especially well illustrated by the discovery of new innate means of resisting viral replication, such as the work on APOBEC3G, TRIM5a, and BST-2/ tetherin presented in this volume.

This volume contains information on the diagnosis, therapy, and prognosis of spinal tumors. Various aspects of different major types of spinal tumors (astrocytomas, ependymomas, and oligodendroglioma) are discussed. Insights into the understanding of molecular pathways involved in tumor biology are explained. Classification of intradural spinal tumors, including the percentages of each of the three major types, is detailed. Symptoms, radiological features, and clinicopathological parameters of spinal cord tumors are explained. Diagnosis, outcome, and prognosis of primary spinal cord and oligodendroglioma are discussed. Diagnosis of some other spinal tumors (e.g., pilomyxoid and chordomas) is also explained. The useful role of neuroimaging in diagnosing spinal teratoid/rhabdoid and gangliogliomas is included. A wide variety of treatments of a number of spinal cord tumor types are presented in detail. Therapies discussed include chemotherapy, surgery, radiosurgery, stereotactic radiosurgery, Cyberknife stereotactic radiotherapy, standard radiation alone, and rhenium-186 intracavity radiation. Also are duiscussed embolozation and spondylectomy. The usefulness of transplantation of human embryonic stem cells-derived oligodendrocyte progenitors and motoneuron progenitors in the repair of injured spinal cord is emphasized. Symptoms of the advent of spinal tumors are pointed out. Introduction to new technologies and their applications to spinal cord tumor diagnosis, treatment, and therapy assessment are explained.

With the explosion of information on autophagy in cancer, this is an opportune time to speed the efforts to translate our current knowledge about autophagy regulation into better understanding of its role in cancer. This book will cover the latest advances in this area from the basics, such as the molecular machinery for autophagy induction and regulation, up to the current areas of interest such as modulation of autophagy and drug discovery for cancer prevention and treatment. The text will include an explanation on how autophagy can function in both oncogenesis and tumor suppression and a description of its function in tumor development and tumor suppression through its roles in cell survival, cell death, cell growth as well as its influences on inflammation, immunity, DNA damage, oxidative stress, tumor microenvironment, etc. The remaining chapters will cover topics on autophagy and cancer therapy. These pages will serve as a description on how the pro-survival function of autophagy may help cancer cells resist chemotherapy and radiation treatment as well as how the pro-death functions of autophagy may enhance cell death in response to cancer therapy, and how to target autophagy for cancer prevention and therapy what to target and how to target it.

PARP Inhibitors for Cancer Therapy provides a comprehensive overview of the role of PARP in cancer therapy. The volume covers the history of the discovery of PARP (poly ADP ribose polymerase) and its role in DNA repair. In addition, a description of discovery of the PARP family, and other DNA maintenance-associated PARPs will also be discussed. The volume also features a section on accessible chemistry behind the development of inhibitors. PARP inhibitors are a group of pharmacological inhibitors that are a particularly good target for cancer therapy. PARP plays a pivotal role in DNA repair and may contribute to the therapeutic resistance to DNA damaging agents used to treat cancer. Researchers have learned a tremendous amount about the biology of PARP and how tumour-specific defects in DNA repair can be exploited by PARPi. The "synthetic lethality" of PARPi is an exciting concept for cancer therapy and has led to a heightened activity in this area.