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Taurine, or 2-aminoethanesulfonic acid, is one of the most abundant sulfur-containing amino acids in the human body. It is found in the heart, brain, retina, and skeletal muscles, and is synthesized in the pancreas. Studies have revealed that taurine is of high physiological importance: it protects against pathologies associated with mitochondrial diseases, and linked processes like aging, metabolic syndrome, cancer, cardiovascular diseases, and neurological disorders. It is also used as a nutritional supplement. Taurine and the Mitochondrion: Applications in the Pharmacotherapy of Human Diseases explores the significance of taurine in the biology of mitochondria. It also explains its role as a pharmacological agent for treating different diseases. Readers will gain an insight into the crucial role it plays in human physiology and the benefits of taurine supplements.Topics covered in this reference include- Synthesis of taurine and its dietary sources- The Role of taurine in mitochondrial health- Taurine as a neurotransmitter- Beneficial effects of taurine in physiological systems such as the reproductive system, renal system, and the gastrointestinal tract- Hepatoprotective and anti-inflammatory properties of taurine- The anti-aging promise of taurine supplementation- Role of taurine supplementation in obesity

Much research has focused on the basic cellular and molecular biological aspects of stem cells. Much of this research has been fueled by their potential for use in regenerative medicine applications, which has in turn spurred growing numbers of translational and clinical studies. However, more work is needed if the potential is to be realized for improvement of the lives and well-being of patients with numerous diseases and conditions.This book series'Cell Biology and Translational Medicine (CBTMED)'as part of Springer Nature's longstanding and very successful Advances in Experimental Medicine and Biology book series, has the goal to accelerate advances by timely information exchange. Emerging areas of regenerative medicine and translational aspects of stem cells are covered in each volume. Outstanding researchers are recruited to highlight developments and remaining challenges in both the basic research and clinical arenas. This current book is the 20th volume of acontinuing series.

This book focuses on both high-density lipoproteins (HDL) metabolism and related diseases from the perspectives of the world-class experts in HDL. Several chapters in this book provide the overall information about HDL metabolism via detailed discussion of HDL structures as well as several key molecules involved in its functions, such as SR-B1 and Cholesteryl Ester Transfer Protein Inhibitors and so on. The rest of this book illustrates the connection between HDL and several diseases that are the major concerns of people's health in many countries, and devotes to exploring the therapies of HDL related diseases. With a better understanding of the HDL metabolism and diseases, this book will benefit the audiences with interest in HDL from biomedicine to clinical practice.

Applications of Nanovesicular Drug Delivery provides thorough insights and a complete and updated discussion on the preparation, properties and drug delivery applications of various nanovesicles. This volume will discuss target-specific drug application, such as ocular, transdermal, nasal, intravenous and oral delivery. This title is a valuable resource for academics, pharmaceutical scientists, including industrial pharmacists and analytical scientists, health care professionals and regulatory scientists actively involved in pharmaceutical products and process development of tailored-made polysaccharides in drug delivery applications. Recently, there have been a number of outstanding nanosystems in nanovesicular carrier-forms (such as nanoemulsions, self-nanoemulsifying systems, nanoliposomes, nanotransferosomes, etc.), that have been researched and developed for efficient drug delivery by many formulators, researchers and scientists. However, no previously published books have covered all these drug delivery nanovesicles collectively in a single resource. - Provides thorough insights and up-to-date discussions about the various systems of nanovesicular drug delivery - Covers advanced trigger-assisted systems (such as iontophoresis, ultra-sound triggering, etc.) and how they have been used for improved drug delivery by nanovesicles - Presents recent advances in drug delivery fields by global leaders and experts from academia, research, industry and regulatory agencies - Includes an updated literature review of relevant key topics, good quality illustrations, chemical structures, attractive flow charts and well-organized tables

Interest in RNA nanotechnology has increased in recent years as recognition of its potential for applications in nanomedicine has grown. Edited by the world's foremost experts in nanomedicine, this comprehensive, state-of-the-art reference details the latest research developments and challenges in the biophysical and single molecule approaches in RNA nanotechnology. In addition, the text also provides in-depth discussions of RNA structure for nanoparticle construction, RNA computation and modeling, single molecule imaging of RNA, RNA nanoparticle assembly, RNA nanoparticles in therapeutics, immunorecognition of RNA nanomaterials, RNA chemistry for nanoparticle synthesis, and conjugation and labeling. Presents the latest research and discoveries in RNA nanotechnology Features contributions from world-class experts in the field Covers RNA nanoparticles in therapeutics Describes self-assembled RNA nanoparticles

Frontiers in Clinical Drug Research - Anti-Cancer Agents is a book series intended for pharmaceutical scientists, postgraduate students and researchers seeking updated and critical information for developing clinical trials and devising research plans in anti-cancer research. Reviews in each volume are written by experts in medical oncology and clinical trials research and compile the latest information available on special topics of interest to oncology and pharmaceutical chemistry researchers.The sixth volume of the book features reviews on these topics:· Immunomodulating Agents in The Treatment of Acute Myeloid Leukemia· Potential Natural Products for Prostate Cancer Management· Inhibition of Key Protein-Protein Interactions by Small Molecules for Cancer Drug Design· Efficacy of Hepatic Arterial Infusion Chemotherapy (HAIC) For Advanced Hepatocellular Carcinoma· Targeting Cancer Stem Cells: Implications in Health and Disease

This book provides a comprehensive coverage of the state of the art in precision medicine in stroke. It starts by explaining and giving general information about precision medicine. Current applications in different strokes types (ischemic, haemorrhagic) are presented from diagnosis to treatment. In addition, ongoing research in the field (early stroke diagnosis and estimation of prognosis) is extensively discussed. The final part provides an in-depth discussion of how different interdisciplinary areas like artificial intelligence, molecular biology and genetics are contributing to this area.Precision Medicine in Stroke provides a practical approach to each chapter, reinforcing clinical applications and presenting clinical cases. This book is intended for all clinicians that interact with stroke patients (neurologists, internal medicine doctors, general practitioners, neurosurgeons), students and basic researchers.

Systemic Drug Delivery Strategies: Delivery Strategies and Engineering Technologies in Cancer Immunotherapy, Volume 2 examines the challenges of delivering immuno-oncology therapies, focusing specifically on the multiple technologies of affective drug delivery strategies. Immuno-oncology (IO) is a growing field of medicine at the interface of immunology and cancer biology leading to development of novel therapeutic approaches, such as chimeric antigen receptor T-cell (CAR-T) and immune checkpoint blockade antibodies, that are clinically approved approaches for cancer therapy. Although currently approved IO approaches have shown tremendous promise for select types of cancers, broad application of IO strategies could even further improve the clinical success, especially for diseases such as pancreatic cancer, brain tumors where the success of IO so far has been limited. This volume of Delivery Strategies and Engineering Technologies in Cancer Immunotherapy discusses methods of targeting tumors, CRISPR technology, and vaccine delivery among many other delivery strategies. Systemic Drug Delivery Strategies: Delivery Strategies and Engineering Technologies in Cancer Immunotherapy, Volume 2 creates a comprehensive treaty that engages the scientific and medical community who are involved in the challenges of immunology, cancer biology, and therapeutics with possible solutions from the nanotechnology and drug delivery side. - Comprehensive treaty covering all aspects of immuno-oncology (IO) - Novel strategies for delivery of IO therapeutics and vaccines - Forecasting on the future of nanotechnology and drug delivery for IO

Leading researchers are specially invited to provide a complete understanding of a key topic within the multidisciplinary fields of physiology, biochemistry and pharmacology. In a form immediately useful to scientists, this periodical aims to filter, highlight and review the latest developments in these rapidly advancing fields.​Chapter “Stationary and Non-Stationary Ion- and Water Flux Interactions in Kidney Proximal Tubule. Mathematical Analysis of Isosmotic Transport by a Minimalistic Model“ is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

Volume Immunodeficiency Diseases in Springer's gold-standard reference work on medical immunology focuses on infectious diseases. In tandem with its three counterpart volumes it offers the most wide-ranging and authoritative repository of knowledge on infectious diseases, with readily accessed contributions by the world's leading authorities on the subject. The encyclopedia covers the material from all angles, with more than 1000 pages of essays on the genetics, physiology, metabolism, pathogenesis and applied microbiology of all known infectious diseases, and includes access to an e-reference work that will include ongoing updates reflecting the latest advances in the field.An outstanding new resource of immense value to a wide range of medical researchers and practitioners, the encyclopedia features a user-friendly subdivision of diseases according to their affective locus in the human body. The sections cover integumentary, skeletal, respiratory, digestive, urinary, and reproductive transmissible pathogens. This high-profile encyclopedia will be an essential addition to academic libraries worldwide.

During the last two decades, stem cells have progressed from merely a concept to a vibrant field of regenerative medicine which is aimed at addressing the root cause of the problem rather than conventional methods of intervention that mostly provide symptomatic relief.Stem cell therapy either alone or in combination with the other established treatment strategies is a hope for patients who suffer from the'incurable'diseases such as Alzheimer, diabetes, myocardial infarction etc. Besides aspirations in the clinical perspective, stem cells provide excellent in vitro disease models for drug development.Given the significance of the field, the proposed book will be a compilation of the bench experience of experts from various research labs involved in the cutting edge area of stem cell research.

Lipids are an integral part of cell membrane architecture, are intermediaries in cell metabolism, and are involved in transmitting cell signals from hormones, growth factors and nutrients. A number of lipases and phospholipases, lipid kinases, lipid phosphatases, sphingosine kinases, and their reaction products have been implicated in fundamental cellular processes including cell proliferation, division and migration. These enzymes and their products underlie the molecular mechanisms of numerous human diseases, in particular metabolic disease (diabetes), cancer, neurodegenerative disease and cardiovascular disease.Over the last decade, studies have advanced to the point that a number of inhibitors for these enzymes have been developed to attempt to ameliorate these conditions; some of the inhibitors are currently in human clinical trial. The need for this book is to review the current status of this field and the prospect for the inhibitors to be clinically important.

This book illuminates mechanisms of resilience. Threats and defense systems lead to adaptive changes in gene expression. Environmental conditions may dampen adaptive responses at the level of RNA expression. The first seven chapters elaborate threats to human health. Human populations spontaneously invade niche boundaries exposing us to threats that drive the resilience process. Emerging RNA viruses are a significant threat to human health. Antiviral drugs are reviewed and how viral genomes respond to the environment driving genome sequence plasticity. Limitations in predicting the human outcome are described in “nonlinear anomalies.” An example includes medical countermeasures for Ebola and Marburg viruses under the “Animal Rule.” Bacterial infections and a review of antibacterial drugs and bacterial resilience mediated by horizontal gene transfer follow. Chapter 6 shifts focus to cancer and discovery of novel therapeutics for leukemia. The spontaneous resolution of AML in children with Down syndrome highlights human resilience. Chapter 7 explores chemicals in the environment. Examples of chemical carcinogenesis illustrate how chemicals disrupt genomes. Historic research ignored RNA damage from chemically induced nucleic acid damage. The emergence of important forms of RNA and their possible role in resilience is proposed. Chapters 8-10 discuss threat recognition and defense systems responding to improve resilience. Chapter 8 describes the immune response as a threat recognition system and response via diverse RNA expression. Oligonucleotides designed to suppress specific RNA to manipulate the immune response including exon-skipping strategies are described. Threat recognition and response by the cytochrome P450 enzymes parallels immune responses. The author proposes metabolic clearance of small molecules is a companion to the immune system. Chapter 10 highlights RNA diversity expressed from a single gene. Molecular Resilience lists paths to RNA transcriptome plasticity forms the molecular basis for resilience. Chapter 11 is an account of ExonDys 51, an approved drug for the treatment of Duchenne muscular dystrophy. Chapter 12 addresses the question “what informs molecular mechanisms of resilience?” that drives the limits to adaptation and boundaries for molecular resilience. He speculates that radical oxygen, epigenetic modifications, and ligands to nuclear hormone receptors play critical roles in regulating molecular resilience.

This book reviews current science and applications in fields including thrombosis and hemostasis, signal transduction, and non-thrombotic conditions such as inflammation, allergy and tumor metastasis. It is a detailed, up-to-date, highly referenced text for clinical scientists and physicians, including recent developments in this rapidly expanding field. More than a scientific resource, this is also an authoritative reference and guide to the diagnosis.

Stem Cell and Gene Therapy for Cardiovascular Disease is a state-of-the-art reference that combines, in one place, the breadth and depth of information available on the topic. As stem cell and gene therapies are the most cutting-edge therapies currently available for patients with heart failure, each section of the book provides information on medical trials from contributors and specialists from around the world, including not only what has been completed, but also what is planned for future research and trials. Cardiology researchers, basic science clinicians, fellows, residents, students, and industry professionals will find this book an invaluable resource for further study on the topic. - Provides information on stem and gene therapy medical trials from contributors and specialists around the world, including not only what has been completed, but also what is planned for future research and trials - Presents topics that can be applied to allogeneic cells, mesenchymal cells, gene therapy, cardiomyoctyes, iPS cells, MAPC's, and organogenesis - Covers the three areas with the greatest clinical trials to date: chronic limb ischemia, chronic angina, and acute MI - Covers the prevailing opinions on how to harness the body's natural repair mechanisms - Ideal resource for cardiology researchers, basic science clinicians, fellows, residents, students, and industry professionals

This comprehensive volume focuses on anti-inflammatory nutraceuticals and their role in various chronic diseases. Food and Drug Administration (FDA) approved drugs such as steroids, non-steroidal anti-inflammatory drugs (NSAIDS), statins and metformin have been shown to modulate inflammatory pathways, but their long-term intake has been associated with numerous side effects. This means that there is enormous potential for dietary agents that can modulate inflammatory pathways in humans. Leading experts describe the latest research on the role of anti-inflammatory nutraceuticals in preventing and treating chronic diseases.

This book provides an unprecedented overview of'Targeted Therapies'for acute myeloid leukemias. It aims at an almost comprehensive coverage of the diverse therapeutic strategies that have been developed during the last decade and are now being evaluated in early clinical trials. Paired and authoritative chapters by leading research scientists and clinicians explain basic concepts and clinical translation of topics that include the underlying genetic and proteomic abnormalities of AML, the development of novel nucleoside analogues, the roles of microRNAs, apoptosis regulators Bcl-2 and p53 and of critical cell signaling proteins such as PIM, FLT3, Raf/MEK, PI3K/AKT/mTOR and aurora kinases. Chapters on epigenetic mechanisms, nuclear receptors, cell surface antigens, the hypoxic leukemia microenvironment, stem cells and leukemia metabolism provide insights into leukemia cell vulnerabilities. Cell therapies utilizing T-, NK- and mesenchymal stem cells and progress in hematopoietic transplantation strategies round up this overview of the multi-dimensional therapeutic landscape in which leukemia specialists develop treatment strategies that are expected to make'leukemia history'in the near future.

The tumor environment is a dynamic network that includes cancer cells, immune cells, fibroblasts, endothelial cells, extracellular matrix, cytokines and receptors. The aim of this book is to summarize the role of these components, especially immune cells, in tumor suppression and/or progression and describe in detail why tumor cells can survive and spread in spite of the antitumor response of immune cells. Since immunotherapy is an attractive approach to cancer therapy, this book also provides information on the two main strategies: monoclonal antibodies and adaptive T cell immunotherapy, with a focus on recent human clinical trials. The book provides a state-of-the-art, comprehensive overview of immune cells in cancer and is an indispensable resource for scientists and medical doctors working and/or lecturing in the field of cancer research and immunology. ​

“Frontiers in Anti-Cancer Drug Discovery” is an Ebook series devoted to publishing the latest and the most important advances in Anti-Cancer drug design and discovery. Eminent scientists write contributions on all areas of rational drug design and drug discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, recent important patents, and structure-activity relationships. The Ebook series should prove to be of interest to all pharmaceutical scientists involved in research in Anti-Cancer drug design and discovery. Each volume is devoted to the major advances in Anti-Cancer drug design and discovery. The Ebook series is essential reading to all scientists involved in drug design and discovery who wish to keep abreast of rapid and important developments in the field.

As the field of medical biotechnology grows with new products and discoveries, so does the need for a holistic view of biotechnology in medicine. Biotechnology in Medical Sciences fulfills that need by delivering a detailed overview of medical biotechnology as it relates to human diseases and epidemiology, bacteriology and antibiotics, virology and

Bioencapsulation (or microencapsulation) of cells and their implantation into a body of immunoprotected cells allows researchers to revive a missing or defective function in the cells. Microencapsulated cells have reached the clinic where they have been shown to be safe and efficacious in numerous clinical trials. Cell types that have been encapsulated for therapeutic purposes include hybridomas, islet cells,'platform'cell lines e.g. HEK293 and CHO cells as well as an increasing focus on the encapsulation of stem cells. This e-book explains the different methods used for achieving cell bioencapsulation based on different polymers e.g. alginate, cellulose sulphate and agarose. Other chapters in this book subsequently describe the use of cell encapsulation in cancer therapy to improve on existing chemotherapies by reducing doses and thus side effects while increasing efficacy for long term in vivo production of (i) tumoricidal or virus neutralising antibodies, (ii) insulin to achieve a self regulating treatment for diabetes and (iii) neuron nurturing factors to treat CNS diseases such as epilepsy, disorders like Parkinson's disease, Alzheimer, Amyotrophic lateral sclerosis, Huntington's disease and pathologies caused by trauma and/or ischemic processes. The book also includes a chapter reviewing the genetic engineering of cells to allow controlled production of biotherapeutics from encapsulated cells. This is a unique and timely book which brings together contributions from some of the leading researchers in the field of cell encapsulation. Interested readers are provided an overview of the exciting developments and clinical experiences of researchers with cell bioencapsulation.

For 10 years the book series Acute Leukemias has been providing updates on the rapid progress being made internationally concerning this group of diseases. The fifth volume mainly addressed experimental approaches, but the present issue presents both therapeutic and prognostic aspects of the most recent results from major multicenter clinical trials. Additional chapters report new trends in leukemia cell biology,the monitoring of minimal residual disease, and secondary leukemias, as well as new antileukemic drugs, antimicrobial strategies, and the use of cytokines. The combined efforts against acute leukemias described in this book explain the recent improvements in the outcome of patients suffering from acute leukemias.

Heparin has been widely used in the medical community as an anti-coagulant. More recently, heparin has been shown to possess other biologically and medically relevant characteristics such as modulation of cell proliferation, inflammation, and cytokine production. In this book, the authors present current research in the study of the properties, uses and side effects of heparin, including the pharmacology of oral heparin; the possible antimetastatic, anti-inflammatory, and suppression of membrane vesiculation effect of heparin; heparin monitoring; searching for heparin binding patterns and heparin-related nanomaterials.

Antiplatelet therapy is the cornerstone of treatment of ischemic cardiovascular disease and over the last few years spectacular advancements in this field have been recorded. This is the first comprehensive handbook entirely dedicated to all the aspects of antiplatelet therapy. The book is divided into three main sections, pathophysiology, pharmacology and therapy, for a total of 23 chapters. A large group of leading experts from different European countries and from the USA, both from academia and industry, have contributed to the book. Besides a detailed overview on the pharmacology and clinical applications of all the currently used or of the novel antiplatelet agents, innovative approaches (e.g. intracellular signalling as an antiplatelet target, small RNAs as platelet therapeutics, etc.) or unconventional aspects (e.g. pharmacologic modulation of the inflammatory action of platelets are also treated. The book is oriented to both basic investigators and to clinicians involved with research on platelet inhibition or with the clinical use of antiplatelet therapies.

This volume arose from the scientific program of the XIIth International Congress of Pharmacology, held in Montreal, Canada, July 24-29, 1994. The scientific program included plenary lectures and symposia, in addition to poster presentations and colloquia. The abstracts of the Congress presentations were published as.supplement 1 of volume 72 by the Cana­ dian Journal of Physiology & Pharmacology. The Congress organizers sought a more expansive treatment of the Congress proceedings and appointed Dr. A. Claudio Cuello to coordinate preparation of the present volume; Dr. Brian Collier was chair of the scientific program committee and, thus, also collaborated on this work. The objective that we pursued was to produce a volume of reasonable size which would feature all of the plenary lectures and symposia from those authors who agreed to participate. To this end, we solicited mini­ reviews from plenary lecturers and asked symposia organizers to coordi­ nate a single short-review covering the individual topics within their event. Those who accepted this challenge are evident in this volume. We express our gratitude to these authors for doing so, and for exercising considerable ingenuity in completing their task within a reasonable time.

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.

Granulocyte colony-stimulating factor (G-CSF or GCSF) is a secreted glycoprotein that stimulates the proliferation and differentiation of granulocyte precursor cells, and induces mobilization of peripheral blood progenitor cells from the bone marrow. Development of recombinant human G-CSF has had a profound impact on the treatment of many diseases, including severe chronic neutropenia and cancer, and has enabled peripheral stem cell transplantation to supplant bone marrow transplantation in the autologous setting. This Milestones in Drug Therapy volume describes the experience of the last 20 years of treatment with recombinant human G-CSF, including the basic science, the use of recombinant human G-CSF in both the oncology and nononcology settings, and the safety and economics of its use. Many of the authors were the original investigators of recombinant human G-CSF and other authors are key researchers who provide their outlook for the next 20 years for use of and research with recombinant human G-CSF.

Antisense technology may result in dramatic changes in the therapy of many diseases and may provide tools to dissect pharmacological processes and to confirm the roles of various genes. In this volume, progress in the understanding of antisense technology and its use in creating new drugs is discussed. Potential caveats, pitfalls and limitations of the technology are also presented. In the next few years the pace at which new molecular targets will be identified will increase exponentially as the sequencing of the human genome and of other genomes proceeds.

This book covers the unique application of flow cytometry in drug discovery and development. The first section includes two introductory chapters, one on flow cytometry and one on biomarkers, as well as a chapter on recent advances in flow cytometry. The second section focuses on the unique challenges and added benefits associated with the use of flow cytometry in the drug development process. The third section contains a single chapter presenting an in depth discussion of validation considerations and regulatory compliance issues associated with drug development.

MicroRNAs (miRNAs), endogenous noncoding regulatory mRNAs of - nucleotides, have rapidly emerged as the central players in gene expression regulation. Owing to their ever-increasing implications in the control of various biological and pathological processes, miRNAs have now been considered novel biomarkers of various human diseases including, cancer, viral disease, cardiov- cular disorders, metabolic disturbances, etc. Particular expression pro?les have been associated with particular pathological states. Expression pro?ling of miR- NAs have therefore become extremely important not only for fundamentalists but also for clinicians. However, the methodologies used for detecting protein-coding mRNAs cannot be directly applied to miRNAs because of their small size. Over the past years, researchers have made great efforts to developing techniques suitable for miRNA detection and quanti?cation; a wide spectrum of creative and inno- tive techniques (more than 30 different methods) have been invented and validated. It has come to the time now to summarize these methods and present them in an orderly manner for better understanding and utilization of these methods to miRNA research and applications. In particular, the development of methods for quantifying circulating miRNAs opens up a fascinating opportunity for realizing miRNA as diagnostic and prognostic biomarkers of human disease. A book on this subject may help boosting up the passion of researchers to further improve the existing techniques and develop more new methods to?t to new application needs. These considerations prompted us and urged us to undertake the work: writing a book focusing on miRNA expression detection methods.

Cancer was thought to originate from alterations in intercellular signaling that resulted in the transformation of cells, their uncontrolled proliferation and metastasis. There is now an increasing body of evidence demonstrating that the surrounding matrix and cell-matrix interactions are also major players in this process. Cells adhere and receive signals from various extracellular matrices via transmembrane receptors, the best known of which are the heterodimeric glycoproteins, integrins.

Chemokine Receptors and NeuroAIDS: Beyond the Co-receptor Function and Links to Other Neuropathologies focuses on unresolved or emerging issues concerning the role of chemokine receptors in neuronal injury and HIV neuropathology, including their ability to regulate fundamental neuronal and glial functions and their role in neurovirulence and neurotoxicity. Although the importance of these molecules in the CNS physiology and pathology is now apparent, these issues are still matter of debate, and further research is required to design effective pharmacological agents that specifically target the brain chemokine system without major side effects. To this end, specific topics have been selected and are reviewed by international experts within the basic science/medical community. This book encourages investigation in the most controversial areas and fosters interaction between clinicians and basic scientists. The book also increases awareness about differences in disease progression among different parts of the world as well as selected patient populations, which may also help identifying novel therapeutic strategies.

An expert guide to targeting protein kinases in cancer therapy Research has shown that protein kinases can instigate the formation and spread of cancer when they transmit faulty signals inside cells. Because of this fact, pharmaceutical scientists have targeted kinases for intensive study, and have been working to develop medicinal roadblocks to sever their malignant means of communication. Complete with full-color presentations, Targeting Protein Kinases for Cancer Therapy defines the structural features of protein kinases and examines their cellular functions. Combining kinase biology with chemistry and pharmacology applications, this book enlists emerging data to drive the discovery of new cancer-fighting drugs. Valuable information includes: Comprehensive overviews of the major kinase families involved in oncology, integrating protein structure and function, and providing important tools to assist pharmaceutical researchers to understand and work in this dynamic area of cancer drug research Focus on small molecule inhibitors as well as other therapeutic modalities Discussion of kinase inhibitors that have entered clinical trials for the treatment of cancer, with an emphasis on molecules that have progressed to late stage clinical trials and, in a few cases, to market Providing a platform for further study, this important work reviews both the successes and challenges of kinase inhibitor therapy, and provides insight into future directions in the war against cancer.

The fact that tumors are composed of both tumor cells and host cells has long been known. These tumor-associated cells include vascular endothelial cells and pe- cytes, as well as inflammatory cells such as neutrophils, monocytes, macrophages, mast cells and eosinophils, and lymphocytes. The tumor cells also interact with stromal cells and with elements of the tissue extracellular matrix. What has been less appreciated is the role that these cells could have in modulating the growth, invasion, and metastasis of the tumor. Early on, the elements of what we now call the tumor microenvironment were considered to be more or less innocent bysta- ers to the role of the tumor cells as they grew and invaded local sites. Today, there is an increased understanding of the critical role of the tumor microenvironment as dramatically influencing the course of tumor development and dissemination. This volume represents a superb compilation of the latest thoughts and data regarding the role of each essential component of the tumor microenvironment in cancer development and progression. Perhaps, the earliest recognition of the role of nonmalignant cells as cancer re- lators was the recognition that lymphocytes can participate in what was termed “immune surveillance” in the 1960s. Our understanding of tumor immunity has improved markedly since then, and there are now successful clinical studies sh- ing the potential use of immune-based therapies in cancer treatment.

Significance of Stem Cells to Tumor Development Cancer stem cells remain a controversial topic and the criteria that define cancer stem cells are continuing to evolve. A recent surge in stem cell research has ignited a field of discovery into many human diseases including diabetes, neuropathologies, and cancer. By replacing specific differentiated cells that have either been lost or died, stem cell therapy proves to be a very promising approach to the treatment of many debilitating diseases. Though stem cells may provide therapeutic benefit under certain conditions, they are also often implicated in the initiation, progression, and therapeutic resistance of malignant disease. This first edition of Stem Cells and Cancer is intended to give a current perspective on the role of stem cells in cancer and strategies for novel therapies directed toward tumor stem cells. The current cancer stem cell hypothesis is presented in several chapters with distinctions made between the hierarchical and stochastic models of tumor cell development.'Stemness,'self-renewal, pluripotency, clonality, and tumorigenicity are important concepts applied towards defining cancer stem cells. Signaling pathways such as Wnt, Sonic Hedgehog, Notch, and Bmi-1 that are involved in differentiation, proliferation, and survival are implicated in the malignant process. Additional chapters address the identification of cancer stem cell populations through the evaluation of molecular markers such as CD133, CD44, and CD24, for example, or by Hoescht dye exclusion to recognize ‘side populations.'Mesenchymal and hematopoietic stem cells are described as well as mouse models that are employed to elucidate the properties and functionality of stem cells in cancer and the stem cell niche. This book encompasses a wide variety of human cancers that include but are not limited to leukemia, gliomas, breast, and prostate cancers. Resistance to conventionaltherapies, genetic versus epigenetic changes that affect therapeutic response and strategies to prevent disease recurrence are challenges have been incorporated into this volume. Stem Cells and Cancer represents a compendium of cutting edge research by experts in the field and will be instrumental in the study of this intriguing line of investigation for many years to come. Rebecca Bagley is a senior scientist at Genzyme Corporation and has worked in the biotechnology industry for 20 years with degrees in biology from Wellesley College and Harvard University. Her expertise in drug development spans a wide range of approaches including immunotherapies, gene and protein therapies, and small molecule delivery with publications in journals such as Molecular Cancer Therapeutics, Cancer Research, and Microvascular Research. Her current research focuses on stem cells, tumor vasculature, and target validation. Dr. Beverly A. Teicher is Vice President of Oncology Research at Genzyme Corporation. Dr. Teicher completed a PhD in Bioorganic Chemistry at the Johns Hopkins University and postdoctoral training at Yale University School of Medicine. Dr. Teicher joined Dana-Farber Cancer Institute as an Assistant Professor of Pathology and rose to Associate Professor of Medicine and Radiation Therapy, Harvard Medical School at Dana-Farber Cancer Institute and Joint Center for Radiation Therapy. Dr. Teicher is an active member of the international scientific community having authored or co-authored more than 400 scientific publications. She has edited eight books, is senior editor for the journal Clinical Cancer Research and is series editor for the Cancer Drug Discovery and Development book series.

In the past two decades, enormous strides have been made These tools for exploring brain biochemistry at the cellular in our understanding of the relationships between inflamma- level opened new vistas for understanding brain functioning tion, innate immune responses, adaptive immune responses, and the pathogenesis of human disease. Using these tools, and degenerative human diseases. The developing informa- our laboratory and that of Joseph Rogers in Sun City d- tion has mostly appeared in specialty journals that have dealt onstrated that HLA-DR was strongly expressed on activated only with isolated aspects of these tightly related fields. As microglia. The identification of HLA-DR, a well-known a result, contemporary scientists have had a difficult time leukocyte marker displayed by antigen presenting cells, on finding sources, even in review articles, that provide an these cells vindicated both Hortega and van Furth. The way integrated picture. This volume, by assembling chapters waspaved for many productive investigations exploring the that demonstrate the relationship between these historically properties of microglial cells and their relationship to infl- separated fields, overcomes that difficulty. There are sec- mation and immune responses. This example of a conju- tions on immunology of the nervous system, diseases that tion between a fundamental concept and technical advances result from immunological dysfunction, current therapeutic to establish its validity has been repeated many times since, approaches, and prospects for the future. Overall, it inte- as the chapters in this volume illustrate.

A clear, straightforward resource to guide you through preclinical drug development Following this book's step-by-step guidance, you can successfully initiate and complete critical phases of preclinical drug development. The book serves as a basic, comprehensive reference to prioritizing and optimizing leads, dose formulation, ADME, pharmacokinetics, modeling, and regulations. This authoritative, easy-to-use resource covers all the issues that need to be considered and provides detailed instructions for current methods and techniques. Each chapter is written by one or more leading experts in the field. These authors, representing the many disciplines involved in preclinical toxicology screening and testing, give you the tools needed to apply an effective multidisciplinary approach. The editor has carefully reviewed all the chapters to ensure that each one is thorough, accurate, and clear. Among the key topics covered are: • Modeling and informatics in drug design • Bioanalytical chemistry • Absorption of drugs after oral administration • Transporter interactions in the ADME pathway of drugs • Metabolism kinetics • Mechanisms and consequences of drug-drug interactions Each chapter offers a full exploration of problems that may be encountered and their solutions. The authors also set forth the limitations of various methods and techniques used in determining the safety and efficacy of a drug during the preclinical stage. This publication should be readily accessible to all pharmaceutical scientists involved in preclinical testing, enabling them to perform and document preclinical safety tests to meet all FDA requirements before clinical trials may begin.

Antiangiogenesis remains a dynamic and evolving field in oncology. New therapeutic targets continue to emerge followed by the rapid development of new therapeutic agents to be investigated in clinical trials. Optimizing the therapeutic potential of antiangiogenic agents in combination with the other therapies in the armamentarium to fight cancer will be an on-going challenge. Antiangiogenic Agents in Cancer Therapy, Second Edition provides a current, up-dated perspective on the state of the art of angiogenesis and therapy with a compendium of scientific findings and approaches to the study of angiogenesis in cancer. Leaders in the field present chapters on such topics as the environmental influences and the genetic and physiologic abnormalities that mediate angiogenesis and its role in the progression of malignant disease, working models of tumor angiogenesis, and the role of angiogenesis inhibition in the therapy of malignant disease in humans. Comprehensive and cutting-edge, Antiangiogenic Agents in Cancer Therapy, Second Edition is an ideal, valuable guide to the most recent advances in the field, and a collection that will be useful for many years to come.

The ambitious goal of this volume is to provide – in chapters written by accomplished scientists and experts in their field – a comprehensive overview of the currently available information related to the therapeutic utility of adult bone marrow-derived cells. With excitement generated almost daily about the possible uses of stem cells to treat human disease, but the controversy surrounding their use still raging, adult bone-marrow derived cells are more readily available, and have a staggering range of uses.

This volume reviews advances in cancer chemotherapy research over the last 10 years. Chapters written by leading experts in their field reflect a range of current medicinal chemistry approaches to small molecule drugs. Each chapter covers the drug target and biological rationale, chemotypes, clinical status and future prospects in this rapidly developing area of drug research.

G-protein coupled receptors (GPCRs) constitute a large superfamily of proteins that have been historically well represented as drug targets. As such, many of the volumes within The Receptors series have focused their attention on rec- tor subfamilies in the GPCR superfamily (e. g., adrenergic, serotonergic, do- minergic). While chemokine receptors are relatively young, in terms of the knowledge that has accumulated regarding their roles in physiology and pat- logy, it is clear that this GPCR subfamily is dwar? ng all others with respect to the total number of receptors and their functional diversity. The breadth of the chemokine? eld was not fully appreciated in the early days of chemokine d- covery, when the characterization of these molecules was largely a curiosity of a small set of biologists primarily interested in in? ammation. Presently, the? eld of chemokinology is quite diverse, and it is nearly impossible to stay informed on all aspects of chemokine biology. Nonetheless, this book seeks to distill information regarding the molecular and cell biology, physiology, and pathology of chemokines and their receptors into a single volume, providing an excellent resource for those entering the? eld or the most experienced c- mokinologist seeking new insights. In the chapters, leading authorities consider structural and cellular aspects of chemokines and chemokine receptors, and more notably, discuss the roles of these molecules in a variety of disease states that transcend their classically de? ned role(s) in in? ammation.

Developments over the past few years have revealed the remarkable versatility of RNA in any compartment of the cell, tasks that had been thought to be exclusively in the realm of proteins and even beyond. The chapters in this book written by leading investigators in the field provide insight into various promising avenues where RNA and nucleic acid derivatives including antisense RNAs, such as siRNA, miRNAs, amplification/selection (SELEX) generated aptamers as well as ribozymes are at the threshold of impacting medicine.

This, the fifth volume in the Proteases in Biology and Disease series, is devoted to Proteases in Gastrointestinal Tissues. Of course, proteases play an important role in the digestion and utilization of ingested proteins, but besides that they elicit a wide range of physiological and pathological effects. Proteases have been recognized as essential regulators, acting both locally and systemically, of normal development, growth and functioning. Dysregulation of protease expression and/or enzymatic activity is often associated with the onset or progression of disease and, thus, proteases represent interesting targets for the pharmacological therapy of e. g. cancer, chronic inflammation, graft rejection, fibrosis, diabetes, vascular disease, and viral or bacterial infections. In addition, changes in the localization, abundance or activity of proteases may serve as informative diagnostic or prognostic markers. This volume focuses on stomach, gut, pancreas, and liver and highlights the role of proteases in normal physiology and disease processes involving these tissues. The first chapter by Nigel W. Bunnett and Graeme S. Cottrell reviews the current knowledge about the protease-activated receptors (PARs) in gastrointestinal tissues. Starting with the mechanisms of activation, signal transduction, and regulation of PAR, their role in controlling gastrointestinal functions and the possible involvement in gastrointestinal diseases are summarized. In Chapter 2, Nikhil I. Khushalani and Nithya Ramnath review the role of matrix metalloproteases (MMPs) and their natural inhibitors, TIMPs, in different types of gastric cancer.

This state-of-the-art reference provides comprehensive coverage of the development of antisense oligonucleotides to inhibit cancer cells as well as those involved in infectious, inflammatory, and immune-mediated diseases-highlighting new tools and technologies in medicinal chemistry, RNA biochemistry, and molecular and cellular biology to produce new therapeutic compounds.Presents previously unpublished data on the use of antisense technology to dissect pharmacological processes and confirm the roles of various genes!Showcasing the benefits of antisense drug use, including reduced toxicity and earlier disease detection, Antisense Drug Technology discussesnovel formulations of antisense drugs practical methods to design effective isotype selective inhibitors molecular mechanisms of antisense drugs mRNA as a current biological template modern postreceptor binding mechanisms and more!With contributions by over 60 seasoned experts in the field and containing more than 3000 helpful references, tables, drawings, and photographs, Antisense Drug Technology is an illuminating source for organic, medicinal, and pharmaceutical chemists; biochemists; geneticists; hematologists; oncologists; molecular and cell biologists; virologists; immunologists; and medical school and graduate students in these disciplines.

Cancer drug discovery has been and continues to be a process of ingenuity, serendip­ ity, and dogged determination. In an effort to develop and discover better therapies against cancer, investigators all over the world have increased our knowledge of cell biology, biochemistry, and molecular biology. The goal has been to define therapeuti­ cally exploitable differences between normal and malignant cells. The result has been an increased understanding of cellular and whole-organism biology and an increased respect for the flexibility and resiliency ofbiologically systems. Thus, as some new therapeutic targets have been defined and new therapeutic strategies have been attempted, so have some new biological hurdles resulting from tumor evasion of the intended therapeutic attack been discovered. Historically, anticancer drugs have originated from all available chemical sources. Synthetic molecules from the chemical industry, especially dyestuffs and warfare agents, and natural products from plants, microbes, and fungi have all been potential sources of pharmaceuticals, including anticancer agents. There is no shortage of molecules; the challenge has been and continues to be methods of identifying molecules that have the potential to be therapeutically important in human malignant disease.'Screening'remains the most important and most controversial method in cancer drug discovery. In vitro screens have generally focused on cytotoxicity and have identified several highly cytotoxic molecules. Other endpoints available in vitro are inhibition of proliferation, 3 inhibition of [ H]thymidine incorporation into DNA and various viability assays, based most frequently on dye exclusion or metabolism.