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This book presents the evidence related to the use of injectable biologics to provide faster and better healing for musculoskeletal lesions and conditions. The authors discuss approaches, such as blood derivatives and cell concentrates, applied to lesions of muscles, ligaments, tendons, bones, meniscus and cartilage, as well as osteoarthritis. Chapters are written by some of the most influential opinion leaders in the field, with up-to-date review of the current literature, where the authors explore both the potential and the limitations of these minimally invasive and promising treatments.The first section is devoted to the formulations and rationale for the use of injectable orthobiologics, while the second section reviews current treatment methods applied to specific joints and pathologies – ranging from tendinopathies through non-unions to articular degenerative processes – as well as the results of these treatment approaches. The third section explores future perspectives, such as pluripotent stem cells, gene therapy, and the stimulation of intrinsic stromal cell niches. Appealing to a broad readership, this book will be of interest to both laboratory research scientists and clinicians, including orthopedists, sports physicians, physiatrists, and regenerative medicine experts.

The temporomandibular joint (TMJ) is a site of intense morbidity for millions of people, especially young, pre-menopausal women. Central to TMJ afflictions are the cartilaginous tissues of the TMJ, especially those of the disc and condylar cartilage, which play crucial roles in normal function of this unusual joint. Damage or disease to these tissues significantly impacts a patient's quality of life by making common activities such as talking and eating difficult and painful. Unfortunately, these tissues have limited ability to heal, necessitating the development of treatments for repair or replacement. The burgeoning field of tissue engineering holds promise that replacement tissues can be constructed in the laboratory to recapitulate the functional requirements of native tissues. This book outlines the biomechanical, biochemical, and anatomical characteristics of the disc and condylar cartilage, and also provides a historical perspective of past and current TMJ treatments and previous tissue engineering efforts. This book was written to serve as a reference for researchers seeking to learn about the TMJ, for undergraduate and graduate level courses, and as a compendium of TMJ tissue engineering design criteria. Table of Contents: The Temporomandibular Joint / Fibrocartilage of the TMJ Disc / Cartilage of the Mandibular Condyle / Tissue Engineering of the Disc / Tissue Engineering of the Mandibular Condyle / Current Perspectives

Cartilage injuries of the knee are common, and diagnosis and treatment options have continued to evolve. This book focuses on current non-operative and surgical treatment strategies for articular cartilage injuries, highlighting the controversies and different approaches from an international perspective. This book includes information on the basic science of cartilage structure and function, expert perspectives on imaging and diagnosing, as well as work-up of athletes and patients presenting with acute or chronic cartilage injury. It also provides an evidence base for current cutting-edge cartilage repair and restoration. Written by leading experts in the field, the book, published in collaboration with ISAKOS and ICRS, is vital reading for orthopaedic and sports medicine surgeons, fellows and residents. It is also of interest to sports trainers, physiotherapists, medical students, postgraduate students, and physical medicine and rehabilitation specialists.

Vascular diseases are the leading cause of death worldwide. Distinguished clinical and surgical approaches have attempted to overcome its morbidity and mortality; still 17.9 million people die every year due to vascular affections. Stem cell therapy has emerged as a promising therapeutic strategy. Stem cells synthesize and secrete cytokines that promote cell recruitment, immunomodulation, extracellular matrix remodeling, angiogenesis, and neuroregeneration, all of which promote regeneration. Besides that, stem cells are also capable of differentiating in various cell types, being employed in tissue engineering. Preclinical and clinical investigations have reported efficacy of stem cell therapy for various vascular diseases. Even though results are encouraging, the studies demonstrate variation in stem cell type and origin, route and protocol for administration, and concomitant use of other treatment strategies, impairing easy interpretation of results and clinical application. The purpose of this book is to compile and comprise the current state of the evidence regarding stem cell therapy for each vascular disease, elucidating possible clinical applications. More than an objective guide for readers on the use of this novel treatment strategy, this publication will advocate for stem cell therapy use and development and will be of significant interest to physicians in a wide range of disciplines as well as researchers.

While the management of meniscal pathology is addressed in many large sports medicine textbooks, this dedicated book on the topic is a major addition to the information currently available for orthopedic surgeons and sports medicine specialists, residents and fellows. As symptomatic meniscal tears remain among the most common musculoskeletal problems that are seen and treated, this up-to-date book on the evaluation and management of meniscal pathology, focused on current techniques and available evidence in the literature, is therefore extremely useful.To that end, The Management of Meniscal Pathology: From Meniscectomy to Repair and Transplantation is a comprehensive resource reviewing all aspects of managing symptomatic meniscal pathology. It is structured to proceed logically through an understanding of the anatomy and biomechanical importance of the meniscus in normal knee kinematics to the evaluation and treatment of meniscal tears and meniscalinsufficiency. The chapters dedicated to the surgical management of meniscal pathology - including partial meniscectomy, meniscus repair, meniscal root repair and meniscal allograft transplantation - include step-by-step descriptions of various operative techniques, including pearls and pitfalls for the reader in addition to classic case examples. Non-operative approaches, as well as novel and emerging strategies and materials, are also highlighted, providing a well-rounded presentation of available techniques and outcomes.

This volume provides a cutting-edge analysis concerning the biology and aetiology, classification, clinical assessment and conservative treatment of lower limb muscle injuries in athletes. Muscle injuries are the most common trauma both in team and individual sports and are responsible for most of the time lost both in training and in competition: in professional football (soccer), they account for 30% and in track and field for 48% of all injuries recorded. Despite the considerable interest in this topic among clinicians and researchers, there is still no consensus regarding the etiopathogenesis, classification, clinical examination and treatment of muscle lesions. Based on the first Italian Consensus Conference on guidelines for the conservative treatment of lower limb muscle injuries in athletes, which was held in April 2017 at Humanitas Clinic Institute in Milan, Italy under the auspices of the Italian Society of Arthroscopy, this comprehensive book addresses the main issues concerning muscle injuries, from biology and pathobiology to clinical evaluation and different treatment option, including the most frequently used physio-kinesitherapy therapies. It also presents a consensus classification of muscle injuries closely linked to prognostic factors. Written by international experts with diverse medical backgrounds, this book offers comprehensive practical guidance for orthopedic surgeons, sports physicians, athletic trainers, physiotherapists, sports science students, and physiatrists.

The present book is an attempt to provide a detailed review of studies that clarify our current understanding of the role of hypoxia in the progression of primary cancer to metastatic disease. It will enable researchers to discover the critical cellular changes that occur under hypoxic conditions and play a role in metastatic dissemination, from the activation of hypoxia-inducible factors, HIF-1 and HIF-2, to the transcriptional profile changes that occur in cancer cells and promote cancer cell survival under detrimental conditions. Readers will discover the methods and challenges involved in imaging and quantifying the degree of hypoxia in a primary tumor. We will provide an understanding of the hypoxia-induced phenotypes that influence heterogeneity, alter the secretome and tumor microenvironment, modify cellular metabolism, and promote immune suppression and resistance to chemotherapy. Finally, we will uncover the therapeutic strategies that are being devised to target the hypoxic microenvironment in the hopes of preventing metastasis and improving the efficacy of standard-of-care cancer treatments. This work is an up to date source of information on the challenges and complexity of the hypoxic tumor microenvironment. Basic and translational scientists, post-doctoral fellows, graduate students, and those interested in how tumors metastasize will find this book a reference that details how hypoxia influences metastatic disease.

This book introduces the exciting field of orthobiology, which will usher in a new array of therapeutic approaches that stimulate the body's natural resources to regenerate musculoskeletal tissues damaged by trauma or disease. The book addresses a range of key topics and discusses emerging approaches that promise to offer effective alternatives to traditional treatments for injuries to bone, cartilage, muscles, ligaments, and tendons. It explains in detail how a variety of innovative products, including biomaterials, growth factors, and autogenous cells, together provide the basis for the regeneration of these musculoskeletal structures and how recent scientific progress has created unique opportunities to address pathological situations that until recently have been treated with unsatisfactory results. The authors are experts from across the world who come together to provide a truly global overview. The book is published in collaboration with ISAKOS. It will be invaluable for all with an interest in this area of medicine, which has already attained huge popularity in Orthopaedics and Sports Medicine and has also attracted the attention of the lay public.

In three Volumes this mini book series presents current knowledge and new perspectives on cartilage as a specialized yet versatile tissue. This second volume is dedicated to basic pathologies of the two most common osteoarticular diseases affecting large segments of the Western population, osteoarthritis and chondrodysplasias. This book addresses Professors, researchers and PhD students who are interested in musculoskeletal and cartilage biology and pathobiology.

This book presents regenerative strategies for the treatment of knee joint disabilities. The book is composed of four main sections totaling 19 chapters which review the current knowledge on the clinical management and preclinical regenerative strategies. It examines the role of different natural-based biomaterials as scaffolds and implants for addressing different tissue lesions in the knee joint. Section one provides an updated and comprehensive discussion on articular cartilage tissue regeneration. Section two focuses on the important contributions for bone and osteochondral tissue engineering. Section three overview the recent advances on meniscus repair/regeneration strategies. Finally, section four further discusses the current strategies for treatment of ligament lesions. Each chapter is prepared by world know expert on their fields, so we do firmly believe that the proposed book will be a reference in the area of biomaterials for regenerative medicine.

​This book, published in cooperation with ESSKA, provides an exhaustive review of the meniscus and its pathology, covering all aspects from the basic science of the normal meniscus to clinical and imaging diagnosis, meniscus repair and meniscectomy, outcomes and complications, postoperative management, and emerging technologies. The book opens by examining in depth aspects such as anatomy, histology, physiology, biomechanics, and physiopathology. Clear guidance is offered on arthroscopy and the classification of meniscal lesions, with consideration of the full range of meniscal pathology, including traumatic lesions, degenerative lesions, root tears, meniscal cysts, and congenital lesions. Choice of treatment in different settings is explained, and the various surgical techniques – meniscectomy, meniscal repair, and reconstruction with allografts – are described in detail with the aid of accompanying videos and with presentation of long-term results. The concluding chapter takes a lookinto the future of meniscus reconstruction, for example through regeneration using mesenchymal stem cells.

This book provides an introductory overview of advancements in platelet-rich plasma (PRP), focusing on current technologies and methods, new challenges and controversies, and avenues for further research. With many studies demonstrating a role for PRP in improving response to injury, this book aims to facilitate the application of this rapidly growing treatment option for trauma patients. Platelet Rich Plasma in Musculoskeletal Practice is a highly informative and carefully presented book, providing scientific and clinical insight for specialists who utilize PRP in daily practice, and for readers who are seeking to learn more about this effective injury treatment.

This comprehensive volume on the blood-gas barrier (BGB) among vertebrates covers its structure and composition along with aspects of evolution, bioengineering, and morphometry. The book also discusses the embryological development of the BGB, including chronology of events and molecular control in vertebrates; modulation of the barrier function, including cyclic stretch-induced increases in alveolar epithelial permeability; mechanisms of lung vascular/epithelial permeability; transport mechanisms of the BGB, including sodium transport channels; factors affecting trans-barrier traffic of fluids, such as chronic elevation of pulmonary microvascular pressure; stress failure; regulation and repair in acute lung injury; chronic lung disease; and lung transportation. Ten authoritative chapters approach the blood-gas barrier holistically, from basic structure and development to pathology and treatment. Properties of the BGB are discussed in the earlier chapters, followed by prenatal and post-natal development and mechanisms of the healthy BGB. The latter half of the book delves into the pathology of the BGB, analyzing common afflictions and exploring options for treatment, including its alterations during lung transplantation. Intuitively structured and comprehensive, The Vertebrate Blood-Gas Barrier in Health and Disease is ideal for researchers and clinicians interested in pneumology and angiology.

This timely desk reference focuses on marine-derived bioactive substances which have biological, medical and industrial applications. The medicinal value of these marine natural products are assessed and discussed. Their function as a new and important resource in novel, anticancer drug discovery research is also presented in international contributions from several research groups. For example, the potential role of Spongistatin, Apratoxin A, Eribulin mesylate, phlorotannins, fucoidan, as anticancer agents is explained. The mechanism of action of bioactive compounds present in marine algae, bacteria, fungus, sponges, seaweeds and other marine animals and plants are illustrated via several mechanisms. In addition, this handbook lists various compounds that are active candidates in chemoprevention and their target actions. The handbook also places into context the demand for anticancer nutraceuticals and their use as potential anti-cancer pharmaceuticals and medicines. This study of advanced and future types of natural compounds from marine sources is written to facilitate the understanding of Biotechnology and its application to marine natural product drug discovery research.

Sports Injuries: Prevention, Diagnosis, Treatment and Rehabilitation covers the whole field of sports injuries and is an up-to-date guide for the diagnosis and treatment of the full range of sports injuries. The work pays detailed attention to biomechanics and injury prevention, examines the emerging treatment role of current strategies and evaluates sports injuries of each part of musculoskeletal system. In addition, pediatric sports injuries, extreme sports injuries, the role of physiotherapy, and future developments are extensively discussed. All those who are involved in the care of patients with sports injuries will find this textbook to be an invaluable, comprehensive, and up-to-date reference.

This volume represents a substantially revised and updated 2nd edition of a reference handbook on major structural components of soft connective tissues and a whole slew of heritable diseases of soft connective tissues. The number of clearly identifiable and distinct disorders has grown somewhat since the 1st edition in 2014, e.g., Ehlers-Danlos syndrome has now 13 entities. A brand new syndrome, Meester Loeys syndrome carrying the name of Bart Loeys was added as a companion to Loeys-Dietz syndrome. Numerous variations of cutis laxa and joint mobility disorders have been discovered taking advantage of recent advancements in genetic analysis. We have acquired better understanding of pathogenesis and biochemical changes in some other, more established entities, such as Marfan and collagen VI myopathies where better management and possible treatment are on the horizon. Even in the case of connective tissue diseases in domestic animals some progress has been made. All these updates werecontributed by a group of distinguished and preeminent physicians and scientists, all of them not just working in the field but making new discoveries described by them.Readers will notice that seemingly there is an overlap among many of these disorders. And indeed, many of them, if not most are interconnected because of the prominent roles of TGFβ, of fibrillin microfibrils and collagen fibril assembly (and other molecules) playing in connective tissues physiology, and by extension in pathogenesis of many disorders described in the book. What I found particularly helpful that author(s) of each chapter bring their own perspective even when described closely related mechanism of the disease. These observations should help with diagnosis and management of such cases.The first chapters are more general, concentrating more on the physiology, structure and biochemistry of normal soft tissues. That should help in better understanding of the pathophysiology. Last but notleast, the chapters are very readable, more like detective stories than dry description of genetic/biochemical defects. I do hope that basic scientists and clinicians with similar and diverse interests alike will appreciate this volume and will be inspired by it to develop their research in the field.

Platelet-Rich Plasma (PRP) has gained tremendous popularity in recent years as a treatment option for specialties including Orthopedics, Dentistry, Sports Medicine, Otorhinolaryngology, Neurosurgery, Ophthalmology, Urology, Vascular, Cardiothoracic and Maxillofacial Surgery, and Veterinarian Medicine. Nowadays, PRP and Stem Cell Science have added an exciting dimension to tissue repair. This book begins by giving the reader a broad overview of current progress as well as a discussion of the technical aspects of preparation and therapeutic use of autologous PRP. It is followed by a review of platelet structure, function and major growth factors in PRP (PDGF and TGFβ).The third chapter outlines the basic principles of biochemical cellular metabolism that increases the efficacy of PRP. Analogous to the preparation of soil for a garden, restoring cellular health should be the first consideration in Regenerative Medicine. Standardization of PRP preparation to clinical use still remains a challenging prospect. In this sense, a feasible strategy for studying PRP preparation is illustrated, which also allows to modulate and tailor the quality of PRP for further clinical applications. The science behind PRP and stem cells, on tissue regeneration, cell proliferation and mesenchyme stem-cells are emphasized and reviewed. Various specific uses of PRP are described with detailed illustrations of various personal experiences mainly in orthopedic injuries, ligament and tendon repair, degenerative diseases, sports medicine, chronic wound healing as well as rehabilitation aspects in tendinopathy. Expertly written by leading scientists in the field, this book provides for beginners and experienced readers scientific fundamentals, the state of art of PRP, specific uses and personal experiences with a practical approach and reference for current trends in use. Finally, this book paves the way for future developments.

Thoroughly discussing the varied elements of meniscal damage and repair, Meniscal Injuries: Management and Surgical Techniques includes the insights and expertise of over 20 leading surgeons and researchers on topics ranging from meniscal anatomy, physical examination, innovative resection and repair techniques, gene therapy, and tissue regeneration. This treatise offers wisdom aimed at assessing true surgical candidates, exploring the intricacies of meniscal composition and function, an overview of meniscal scaffolds and replacements, and patient examination pearls. Also discussed in depth is cutting edge research concerning meniscal repair enhancement, nanofiber technology as a means of meniscal replacement, and biologic agents directed toward chondral protection. All the science presented will direct the sports medicine practitioner to state-of-the-art treatment aimed at knee preservation. Meniscal repair and regeneration is a rapidly evolving science - earlyattempts at meniscal restoration or repair resulted in short-term gains which often sacrificed long-term joint integrity. Now, the practitioner is afforded numerous means of retaining or restoring meniscal tissue. Breakthroughs in scaffold and allograft replacement, as featured herein, offer the promise of articular cartilage preservation like never before. In addition, tissue regeneration and gene therapy techniques, featured throughout, offer a glimpse into emerging technologies aimed at preserving or replacing meniscal tissue in previously considered “hopeless” cases. As such, Meniscal Injuries will be an indispensible resource to orthopedic surgeons and sports medicine practitioners interested in providing the absolute most contemporary and evidence-based care to their patients.

In metastasis, tumor cells disseminate from the primary lesion and home to secondary organs where they may remain dormant for a long time. Metastasis formation is still the most feared manifestation for tumor patients and clinicians. Although improvements have been made concerning earlier detection and specific therapy, most of the cancer patients still die of distant metastases. The pu-rpose of these three volumes is to review the recent progress in molecular metas­ tasis research and to attempt to further understand the biol­ ogy of this multifocal process. With respect to present day molecular biology, the pioneers of metastasis research established the basic concepts of metasta­ sis formation in the 1970s and 1980s, namely, clonal selection of metastatic cells, heterogeneity of metastatic subpopulations, organ specificity of metastasis and the importance of angio­ genesis (Fidler, Kripke, Nicolson, Folkman and others). In the 1980s and 1990s, several of the molecules involved were identified and their network interactions elucidated. These three volumes of Current Topics in Microbiology and Immuno­ logy compile the most recent developments on these meta­ stasis-related molecules; their interactions, regulation, and ways to interfere with their action. It became evident that metastasis-related molecules are confined to distinct cellular compartments, such as the extracellular space, the cell membrane, the cytoplasmic signalling network, and the nuclear regulatory system. For the complex metastatic cascade, proteolysis and alterations in adhesive functions are the most obvious and thus one of the most thoroughly investigated processes.

Advances in molecular biology describing important enzyme systems involved in drug conjugation and deconjugation reactions and recent work indicating the importance of drug and xenobiotic conjugates as transport forms of biologically active compounds are reviewed comprehensively. Part One describes molecular events associated with the expression and regulation of transferases and hydrolases involved in Phase II drug conjugation and deconjugation. Part Two deals with the regulation of Phase II conjugation, and Part Three reviews critically the importance of drug conjugates in pharmacology and toxicology. This volume is an up-to-date source of information on this topic and will be of broad interest to pharmacologists and toxicologists.

Brain edema is found in a wide variety of clinical disorders including stroke, intracerebral haemorrhage, subarachnoid haemorrhage, head injury, brain tumors and hydrocephalus. This volume brings together clinical and basic scientists from all over the world. Their expertise in the understanding of brain edema and shifts in brain water compartments has led to a further significant step in our understanding of those diseases characterized by brain edema. This book has also drawn on the expertise of the International Advisory Board of the Brain Edema Society, who have carefully summarized each section, thus providing an easy-to-read summary of the latest advances in each subject. The book is therefore much more than a collection of papers: it represents a critical appraisal and puts each paper into modern scientific context. The greatest advances have come from the rapid development of modern imaging techniques, especially with magnetic resonance imaging (MRI). Imaging can now produce'water maps” and'metabolic profiles” that bring brain metabolism and water content right into every clinic with access to MRI. This book provides the background knowledge to understand these pathophysiological changes.

How to protect against ischemia/reperfusion damage is one of the most urgent problems in medicine. It is known that ischemic damage can be attenuated by improving the oxygen balance of the ischemic heart, but the damage-producing mechanism is not yet fully understood. This book provides the latest information on the pathophysiology of ischemia/reperfusion damage and presents new ideas for more effective methods for protection. In the first two sections, the roles of such factors as various ions and phospholipids that modulate ischemia/reperfusion damage are explored, providing a clear and updated explanation of the mechanisms involved. In the third section, the myocardial and vascular remodeling procedure in hearts that have undergone ischemia/reperfusion is explained in terms of signal transduction, enabling a new understanding of the remodeling process. In the final section, a new approach to protection against ischemia/reperfusion damage is presented.

Prophylaxis and treatment of thromboembolism have made one of the major impacts in medicine. Heparin has widely been used as the most effective drug during the last 50 years. However, its potential side effects have led to the search for equally effective but safer alternatives. At present, the low-molecular-weight heparins are the most promising steps in this direction. Considerable interest has been generated at the same time in exploring other gly­ cosaminoglycans of the nonheparin type for therapeutic use. The existence of these com­ pounds has been known for a long time and substantial information has been gathered on glycosaminoglycans such as heparinsulfate, dermatansulfate, and chondroitinsulfate. Many of these substances are derived from animal or plant sources, and some of them have now been synthesized. The aim of the Fourth Symposium on Glycosaminoglycan Research at Villa Vigoni in Loveno at Lake Comolltaly was to summarize the considerable new information in this field. The articles of the present volume are mainly based on a German-Italian collaboration supported by the Vigoni Program. The selected articles describe many different, nonheparin glycosaminoglycans, some of them already in clinical trials as antithrombotic agents. In particular, the interaction of glycosaminoglycans with some cellular elements of blood, especially leukocytes and platelets, are discussed. New methods for their identification and assays are described and considerable emphasis is placed on the pharmacokinetic aspects of these new compounds. Particularly, some nonanticoagulant activities of the glycosamino­ glycans are discussed in detail.

Resistance to treatment represents the final common outcome for far too many patients with cancer. Even our most promising new drugs fall victim to drug resistance. Hormones and newer biological therapies, though safe and active, also lose their activity over time. In this volume of Drug Resistance, leading investigators in the field have reviewed the most basic mechanisms of drug resistance, and have proposed ways to modulate resistance. This comprehensive volume should be of value for basic and clinical scientists who wish to delve more deeply into this intriguing problem in the laboratory and devastating problem in the clinic.

Endothelial cell biology has developed into a vibrant discipline and has become a critical instrument to study several disease processes on the cellular and molecular level. It is now widely recognized that dysfunctions of normal endothelial cell homeostasis are involved in some of the most important human diseases, including ischemic heart diseases, hypertension, atherosclerosis, tumors, diabetes, arthritis, and inflammation. Further, the increasing importance and recognition of the field of vascular biology in general requires in vitro and in vivo techniques in order to address the complex questions. Methods in Endothelial Cell Biology is a comprehensive practical'how-to'-guide summarizing the most relevant established techniques as well as a number of new emerging techniques. Easy-to-follow reliable protocols provide a useful lab bench resource for the experienced researcher and newcomer to the field.

Mammary Tumor Cell Cycle, Differentiation and Metastasis is the fifth volume since 1988 in a series designed to broadly examine current advances in the cellular and molecular biology of breast cancer. As in previous volumes, the editors have invited recognized experts in cutting-edge topics to provide a chapter focused on their area of research. The editors have turned to the researchers who study rodent models of the disease and to those who study the cellular and molecular basis of human breast cancer. The first section of the book is devoted to new mouse models of mammary development and tumorigenesis. The second section moves to studies of human breast cancer and focuses on receptors, signalling, and the cell cycle. The final section deals with defective tissue interactions in human breast cancer. We are now in a period of extremely rapid accumulation of data on the molecular and cellular biology of breast cancer. These findings are highlighted in chapters from Mammary Tumor Cell Cycle, Differentiation and Metastasis: Advances in Cellular and Molecular Biology of Breast Cancer.

There has been an explosion of research activity related to angiogenesis in recent years, and hundreds of laboratories worldwide are actively involved in many aspects of angiogenesiS. The literature on angiogenesis increases exponentially every year, and more than 16,000 peer-reviewed articles have been published the past 25 years, which are scattered in basic science and clinical journals. The complexity of the cascade of events leading to new vessel formation from preexisting ones has challenged scientists in cell biology, biochemistry, physiology, pharmacology, molecular biology, developmental biology, and other fields. With their multidisciplinary approach and the powerful new techniques that have been developed, the progress in understanding angiogenesis has been impressive indeed. Only 12 years ago the mention of an angiogenic factor caused skepticism. Today we have the complete amino-acid fiequence and their genes cloned for at least 9 angiogenic factors. Many laboratories are studying their role in angiogenesis, and several biotechnology firms have a keen interest in commercial developments relative to these molecules. The role of extracellular matrix components in angiogenesis and the interaction of endothelial cells with other cell types such as pericytes, smooth muscle cells, and inflammatory cells have been studied by other groups. This rapid expansion is the result of a realization that in many disease states a common underlying pathology is a derangement in angiogenesis.

This volume'Angiogenesis in Brain Tumors'is part of the book series'Cancer Treatment and Research'and offers a detailed overview of the biology of angiogenesis in the central nervous system, the role of angiogenesis in brain tumor development and growth, and anti-angiogenic therapeutic applications. Our understanding of the mutual relationship between tumor growth and concomitant neovascularization has provided important insights into the biology of brain tumors and contributed to the development of new treatment strategies. Many of the early experimental findings on angiogenesis were made using brain tumor models. This was largely due to the fact that brain tumors are among the highest vascularized tumors. In addition, until to date all efforts to develop efficient therapies for these highly malignant tumors have met with little if any success. The scientific evidence on the role of angiogenesis in tumor development accumulated until today has already let to the initiation of several clinical trials. Despite the fact that not all expectations have been fulfilled, the results available so far are promising and suggest that anti­ angiogenic therapeutic strategies may be of benefit to our brain tumor patients in the near future. The volume is comprised of four sections. The first section is dedicated to the principles of angiogenesis in the central nervous system and gives an overview on the cellular, physiological and developmental processes of angiogenesis.

Presenting patient- and problem-oriented review articles, this series is designed to keep the internist, general surgeon, and specialist in gastroenterology and hepatology abreast of the latest advances in the field.

Substantial data indicate the broad importance of vitamin D-based signaling in normal human physiology and the broad effects of vitamin D deficiency. Vitamin D may play a role not only in the control of bone and mineral metabolism, but also appears to be involved in immune function, cardiovascular health, thrombosis and vasculogenesis and neuromuscular function. Considerable epidemiologic data demonstrate that low vitamin D serum levels occur very commonly in normal adult populations and that vitamin D deficiency is associated with an enhanced risk of cancer death from lung, prostate, head & neck, colorectal and other gastrointestinal cancers. In addition, preclinical data provide evidence that calcitriol and other active analogues of calcitriol have anti-proliferative, pro-differentiative, pro-apoptotic and anti-angiogenic activity in numerous in-vitro and in-vivo models. It is quite clear that, while it requires high exposure to calcitriol to induce these effects, such exposure can be readily achieved when high dose intermittent therapy is given.

Knowledge of the extracellular matrix (ECM) is essential to understand cellular differentiation, tissue development, and tissue remodeling.This volume of the series “Biology of Extracellular Matrix” provides a timely overview of the structure, regulation, and function of the major macromolecules that make up the extracellular matrix. It covers topics such as collagen types and assembly of collagen-containing suprastructures, basement membrane, fibronectin and other cell-adhesive glycoproteins, proteoglycans, microfibrils, elastin, fibulins and matricellular proteins, such as thrombospondin. It also explores the concept that ECM components together with their cell surface receptors can be viewed as intricate nano-devices that allow cells to physically organize their 3-D-environment. Further, the role of the ECM in human disease and pathogenesis is discussed as well as the use of model organisms in elucidating ECM function.

Squamous epithelia form the lining surface of tissues in contact with the environment: the skin, oral mucosa, esophagus and respiratory tract, the genital tract, and several other specialized tissues. These tissues are at highest risk for exposure to environmental carcinogens such as UV, tobacco smoke and infectious agents. Cancers that form in squamous epithelia are among the most common human solid tumors and have high morbidity and mortality. These cancers include squamous cell carcinoma of the skin, oral cancer, head and neck and esophageal cancer, certain lung cancers and cervical cancer. We propose to organize the book so that the early chapters will focus on individual pathways and more specific mechanisms in both normal function and cancer, while the later chapters will be more integrative and include overviews of biomarkers and therapeutic development. This should increase interest for clinically oriented researchers. All authors will be encouraged to provide a balanced review in addition to highlighting their own work.

This book reviews the epidemiological associations between insulin resistance and cancer. This is followed by reviews of animal models which support this relationship and provide insight into potential mechanisms. Several chapters then provide detailed examination of the cellular and molecular changes characterizing the insulin resistant state, such as hyperinsulinemia, abnormal metabolism and hormone signaling, and how these interact with various tumor characteristics. For example some tumors present increased quantities of the fetal form of the insulin receptor, unique regulation of oxidative (Krebs'cycle) metabolism (Warburg effect), as well as mutations in various relevant signaling pathways. Finally, the clinical implications of these data are integrated with considerations of insulin “sensitization” and potential metabolic interventions to prevent and treat cancer. It should be noted that while a number of cancers are associated with obesity the authors here have focused primarily on breast cancer as a key and significant model.

Squamous cell carcinoma of the oral cavity (SCCOC) is one of the most prevalent tumors of the head and neck region. Despite improvements in treatment, the survival of patients with SCCOC has not significantly improved over the past several decades. Most frequently, treatment failure takes the form of local and regional recurrences, but as disease control in these areas improves, SCCOC treatment failures more commonly occur as distant metastasis. The presence of cervical lymph node metastasis is the most reliable adverse prognostic factor in patients with SCCOC, and extracapsular spread (ECS) of cervical lymph nodes metastasis is a particularly reliable predictor of regional and distant recurrence and death from disease. Decisions regarding elective and therapeutic management of cervical lymph node metastases are made mainly on clinical grounds as we cannot always predict cervical lymph node metastasis from the size and extent of invasion of the primary tumors. Therefore the treatment of the neck disease in the management of SCCOC remains controversial. The promise of using biomarker-based treatment decisions has yet to be fully realized due to our poor understanding of the mechanisms of regional and distant metastases of SCCOC. We will summarize the current status of investigations into SCCOC metastases and potential of these studies to impact basic research investigators and clinicians confronting SCCOC in the future.

This clinical guide provides a special focus on the normal meniscal mechanism, body and function. Meniscal pathology and therapy are depicted in detail, followed by the presentation of long-term experience of meniscal transplantation and a look into the future of meniscal surgery. During the last few decades, as the management of meniscal trauma has evolved, and knowledge gained on meniscal function, the orthopaedic surgeon has attempted to preserve the meniscus whenever possible. Arthroscopic meniscal repair has become the treatment of choice when the tear is located in the peripheral rim. Partial meniscectomy has become limited to such an extent that the deleterious effect of total meniscectomy is avoided. Meniscal allograft replacement, which has been available for the last two decades, is used when the patient is confronted with a painful total meniscectomy. Future research and experiments may suggest that partial meniscal replacement might be indicated in the presence of a painful knee compartment after failed meniscal repair or partial meniscectomy.

Glioblastoma is the most malignant brain tumor that still remains incurable. It is such a deadly disease that patients do not survive more than a few months after diagnosis. Our understanding of the histopathology and molecular mechanisms of formation of glioblastoma is rapidly advancing so as to provide us clues for devising rational therapeutic strategies for treatment of this malignancy. It is important that we continue to improve our knowledge about the pathogenesis of this devastating disease and explore new areas to find successful therapeutic strategies. Various approaches such as sophisticated imaging techniques, improved surgical procedures, ground-breaking strategies for radiotherapy, chemotherapy, immunotherapy, chemoimmunotherapy, and photodynamic therapy are being used for eradicating glioblastoma. Hopefully, this book will be an important source of information on glioblastoma and therefore be highly useful to the students, postdoctoral fellows, principal investigators, and clinicians involved in this field.

This book presents the latest findings in the field of research of mechanosensitivity and mechanotransduction in different cells and tissues. Mechanosensitivity and mechanotransduction of the heart and vascular cells, in the lung, in bone and joint tissues, in sensor systems and in blood cells are described in detail. This Volume focuses on molecular mechanisms of mechanosensitivity and mechanotransduction via cytoskeleton. Integrin-mediated mechanotransduction, the role of actin cytoskeleton and the role of other cytoskeletal elements are discussed. It contains a detailed description of several stretch-induced signaling cascades with multiple levels of crosstalk between different pathways. It contains a description of the role of nitric oxide in regulation of cardiac activity and in regulation of mechanically gated channels in the heart. In the heart mechanical signals are propagated into the intracellular space primarily via integrin-linked complexes, and are subsequently transmitted from cell to cell via paracrine signaling. Biochemical signals derived from mechanical stimuli activate both acute phosphorylation of signaling cascades, such as in the PI3K, FAK, and ILK pathways, and long-term morphological modii cations via intracellular cytoskeletal reorganization and extracellular matrix remodelling. Cellular and molecular effects of mechanical stretch on vascular cells are also discussed. This Volume highlights the role of mechanotransduction in the lung, in bone and joint tissues. For the first time mechanosensitivity and mechanotransduction in blood cells are discussed. It contains new insights into mechanosensitive K+ channels functioning in mouse B lymphocytes. This book is a unique collection of reviews outlining current knowledge and future developments in this rapidly growing field. Currently, investigations of the molecular mechanisms ofmechanosensitivity and mechanotransduction are focused on several issues. The majority of studies investigate intracellular signaling pathways. Knowledge of the mechanisms which underlie these processes is necessary for understanding of the normal functioning of different organs and tissues and allows to predict changes, which arise due to alterations of their environment. Possibly such knowledge will allow the development of new methods of artificial intervention and therapies. This book brings up the problem closer to the experts in related medical and biological sciences as well as practicing doctors besides just presenting the latest achievements in the field.

Pushed by the progress of biology, technology and biomechanics, knee surgery has dramatically evolved in the last decades. This book is a'state of the art'concerning all aspects of knee surgery from ligament reconstruction to Total Knee Arthroplasty. An international panel of renowned authors have worked on this didactic fully illustrated book. It will help young surgeons to understand basic sciences and modern sugical techniques. The experienced surgeon will find help to deal with difficult cases and clarifications in recent technologic advances such as cartilage surgery, navigation and mini invasive surgery.

The temporomandibular joint (TMJ) is a site of intense morbidity for millions of people, especially young, pre-menopausal women. Central to TMJ afflictions are the cartilaginous tissues of the TMJ, especially those of the disc and condylar cartilage, which play crucial roles in normal function of this unusual joint. Damage or disease to these tissues significantly impacts a patient's quality of life by making common activities such as talking and eating difficult and painful. Unfortunately, these tissues have limited ability to heal, necessitating the development of treatments for repair or replacement. The burgeoning field of tissue engineering holds promise that replacement tissues can be constructed in the laboratory to recapitulate the functional requirements of native tissues. This book outlines the biomechanical, biochemical, and anatomical characteristics of the disc and condylar cartilage, and also provides a historical perspective of past and current TMJ treatments and previous tissue engineering efforts. This book was written to serve as a reference for researchers seeking to learn about the TMJ, for undergraduate and graduate level courses, and as a compendium of TMJ tissue engineering design criteria. Table of Contents: The Temporomandibular Joint / Fibrocartilage of the TMJ Disc / Cartilage of the Mandibular Condyle / Tissue Engineering of the Disc / Tissue Engineering of the Mandibular Condyle / Current Perspectives

This volume presents the proceedings of the 7th Asian-Pacific Conference on Medical and Biological Engineering (APCMBE 2008). Themed'Biomedical Engineering – Promoting Sustainable Development of Modern Medicine'the proceedings address a broad spectrum of topics from Bioengineering and Biomedicine, like Biomaterials, Artificial Organs, Tissue Engineering, Nanobiotechnology and Nanomedicine, Biomedical Imaging, Bio MEMS, Biosignal Processing, Digital Medicine, BME Education. It helps medical and biological engineering professionals to interact and exchange their ideas and experiences.

Without metastasis, prostate cancer would be both tolerable and treatable. The high incidence of indolent and organ confined disease is testament to this sweeping generalisation. Equally, if molecular markers of metastatic spread can be identified, then the choice of treatment for many patients would be easier and more radical, even curative. However, should prevention and treatment of the primary tumors prove difficult or impossible, then a knowledge of the phenotype of advanced metastatic tumors should allow us to target these lesions for destruction by conventional (drug based) or more innovative means such as gene and/or immunotherapy (1). The process of metastasis has been reviewed many times (e. g., 2) and has been subdivided for ease of analysis into a number of discrete stages (see Figure 1). It has been suggested that at least 10 separate genetic 2. ECM degradation: migration MMP ; Integrin ; TIMP 3. Intravasation MMP TIMP 1. Cellular independence 4. Transport Adhesion loss and evasion (E Cadherin) of host immune system MHCClass1 ICAM-1 to block T cell receptor 5. Arrest of movement: endothelial adhesion CD44 or switch 6. Extravasation to colonise new site 7. Proliferation at Laminin R distant site to form Integrin switch METASTASIS Figure 1. Stages in prostate cancer metastasis. Basic processes in tumor metastases are indicated in the boxes with some key changes in gene expression indicated at each stage by the solid arrows.

In this book, a worldwide panel of leading experts discuss the role of inflammation in the pathogenesis of major chronic diseases and the current controversy regarding risk versus benefit of selective cyclooxygenase-2 (COX-2) inhibitors. The authors provide exciting and enlightening perspectives on COX-2 and related molecular targets in the future of medicine, including historical perspectives.

Epithelial phenotype is a dynamic stage of differentiation that can be modulated during several physiological or pathological events. The rapid conversion to a mesenchymal-like phenotype is called an epithelial-mesenchymal transition (EMT). The Rise and Fall of Epithelial Phenotype is the first book to comprehensively introduce the concept of EMT. The first part of this volume describes main examples and models and explains their physiological relevance. These examples include hydra morphogenesis, gastrulation in mouse, drosophila and sea urchin, as well as neural crest cell migration and heart morphogenesis in vertebrates. Part two reviews in detail, specific EMT molecular pathways covering extracellular induction, transduction and transcription response and modulation of cell-cell adhesion structures. It emphasizes new specific pathways with potential medical applications. EMTs can also be linked to pathological events such as wound healing and cancer progression, as detailed in this section of the book.

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