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Peritoneal Tumor Microenvironment of Cancers on Cancer Hallmarks: Perspectives of Translational Medicine provides readers with cutting-edge knowledge on tumor microenvironment. By exploring multiple aspects on tumor microenvironment, it gives an integrative insight on cancer diseases ranging from diagnosis to prediction of prognosis and individualized treatment.The book discusses topics such as clinical significance of tumor microenvironment, tumorigenesis and cancer progression, histopathological features of cancer in peritoneum, immune cells in tumor, exosomal cell-to-cell interactions, and therapeutic approaches to target tumor microenvironment. Additionally, it discusses tumor evolution during chemotherapy and metastasis, and future perspectives on identification and validation of biomarkers using liquid biopsy.This book is a valuable resource for cancer researchers, oncologists, medical doctors, and several members of biomedical field who want to understand the complex microenvironment of peritoneal tumors. - Discusses how to apply tumor microenvironment knowledge to diagnosis, prediction of prognosis, and individualized treatment of cancer - Provides readers with up-to-date knowledge on translational medicine, focusing on bench-to-bedside approach for cancer treatment and diagnosis - Presents collaborative research works from the perspectives of medical doctors, cancer researchers, basic biological scientists, and bioinformaticians to provide integrative insights on tumor microenvironment

Sinusoidal Cells in Liver Diseases: Role in their Pathophysiology, Diagnosis, and Treatment provides a state-of-the-art review on recent advances surrounding the role of liver sinusoidal cells (LSECs, HSCs, macrophages, and other non-parenchymal cells) in acute and chronic liver diseases. Coverage emphasizes disease pathophysiology, novel mechanisms, unmet clinical questions, development of biomarkers and treatment opportunities. By focusing on the role of sinusoidal cells in human liver diseases, this reference provides a comprehensive overview of the role of sinusoidal cells in acute and chronic liver diseases, in its pathophysiology and mechanisms, and in the development of novel biomarkers and new therapeutics. Cells of the liver vasculature play an essential role in the pathophysiology of acute and chronic liver diseases and are considered key therapeutic targets to treat most of human hepatopathies. Coverage in this reference includes the phenotypic changes occurring in liver vascular cells and how cells contribute to the development of microcirculatory dysfunction, fibrosis, inflammation, and liver failure. Provides a comprehensive update on the role of sinusoidal cells in acute and chronic liver diseasesCovers our current understanding of the role of sinusoidal cells as therapeutic targets to improve liver diseasesPresents the latest research in the development of novel biomarkers of liver diseases that derive from sinusoidal cells

Biochemistry of Drug Metabolizing Enzymes: Trends and Challenges is a complete and well-integrated reference on their mechanisms of action, their role in diseases, agents responsible for their deactivation, and their malfunction. Chapters explain the biochemistry of DMEs, including biochemical activation, functions, computational approaches, different contaminants on the action and function of DMEs, and describe the importance of DMEs in the drug development process. Conditions covered include metabolic diseases, cardiovascular diseases, neurological diseases, physiological diseases, xenobiotics and inflammatory responses, and their contribution in the malfunctioning of drug metabolizing enzymes. This book is the perfect resource for pharmacology and biochemistry researchers to understand the principles of DMEs. Researchers in the corporate environment will also benefit from the comprehensive list of diseases associated with malfunction of DMEs. - Includes extensive classification of DMEs, their mechanism of action and computational analysis - Covers the biotransformation of drug by DMEs and the possible impact of environmental contaminants - Discusses the activity of DMEs in different clinical conditions such as cardiovascular disease, metabolic disorders, inflammation and neurotoxicity - Includes modern and novel bioanalytical techniques to predict the effect of DMEs

Nanotechnology seeks to exploit distinct technological advances controlling the structure of nanoscale biomaterials at a nanodimensional scale approaching individual molecules and their aggregates or supramolecular structures. The term'nanomedicine'is used to describe those technologies under the umbrella of nanotechnology that have therapeutic applications in human health. This book presents recent trends and research achievements in the field of pharmaceutical nanotechnology and advanced drug delivery nanosystems, especially for theranostic purposes. The applications of drug delivery nanosystems considered carriers of active pharmaceutical ingredients (APIs) (e.g., proteins, peptides, and nucleic acids) are analyzed on the basis of technology, preparation protocols, and biomedical applications. The book also extensively reports on the principles, design protocols, and applications of nanosystems in drug delivery, imaging, and targeting of active molecules of pharmaceutical interest.

HCC is the most common primary cancer of the liver and according to the WHO report, the fourth commonest cause of death. The estimated incidence of new cases worldwide is about 500,000-1,000,000 per year causing 600,000 deaths globally per year. Although there are large areas of the world where the incidence of HCC is still unknown, several countries in East Asia and some Sub-Saharan African regions are affected by a very high prevalence of HCC (over 20 cases/100,000 population). Areas with a moderately high risk (11-20 cases/100,000 population) include Italy, Spain and Latin America, while France, Germany and the United Kingdom have instead an intermediate risk (5-10 cases/100,000 population). A relatively low prevalence (less than 5 cases/100,000 population) is found in the United States, Canada and Scandinavia. The incidence of HCC has been rising in developed western countries in the last two decades, along with the emergence of the hepatitis C virus infection and due to the rise of immigration rates from HBV-endemic countries. In addition, even though the incidence of HCC reaches its highest peak among persons over 65 years, an increased incidence among younger individuals has been noted in the last two decades both in USA and Europe. A multidisciplinary approach should be taken when assessing patients with HCC; stage of HCC and liver disease should always be taken into account and the best treatment should be offered. Liver resection and ablative treatments should never be denied to patients, and curative procedures should be performed in hepato-biliary-pancreatic centers. Each HCC patient has to be evaluated singularly, stratifying each time the risk for the procedure so as to determine which treatment is the best treatment. It is also important to analyze all the possibilities that can be offered. This similar approach showed a good efficacy and safety in all “frail” patient categories, such as elderly patients or patients with HCC and HIV infection. Early diagnosis of HCC and retreatment for HCC recurrence have a key role in the survival of patients. Therefore, regular screening programs for HCC should be extended to all patients according to proposed guidelines, together with a greater proclivity for treatment and retreatment options in cases of an HCC diagnosis or recurrence. This may be an important and needed breakthrough for this rising problem.

In the last few years, human metabolic disorders have become some of the most prevalent and prejudicial diseases worldwide. Hepatic steatosis, among many health problems, has several risk factors related to the disease prognosis such as obesity, nutritional problems, diabetes, hypertension, hyperuricemia and even sleep apnea. Alcohol abuse also can lead to a severe liver-steatosis state. The progression of hepatic steatosis can lead to complications such as cryptogenic cirrhosis and hepatocellular carcinoma. Drug therapy has instead been focused on the mitigation of risk factors, however, new potential therapeutic perspectives are being discussed. This book presents the origins, diagnosis and epidemiology of hepatic steatosis with new perceptions. The authors also aim to show the molecular basis and signaling involved in liver disorders, discussing the inflammatory process, lipid metabolism and angiogenesis mechanisms. The role of nutrition in the treatment and development of steatosis was also presented and new advances were highlighted. Recent studies revealed the need for the use of bariatric surgery, functional foods and the modulation of endogenous systems, such as the sirtuins and renin-angiotensin systems, to treat liver disease. In this context, we aimed to introduce, review and discuss one of the most widespread metabolic disorders in the world: hepatic steatosis and its repercussions.

This book presents recent findings on the role of oxidative stress in chronic diseases. Understanding the mechanisms behind it enables readers to comprehend the rationale which underlies intervention in such conditions. The book places special emphasis on genetic polymorphism-an important issue related to this field of study. It covers the role of

Calcium Binding Proteins explains the unique and highly diverse functions of calcium in biology, which are realized by calcium binding proteins. The structures and physical characteristics of these calcium binding proteins are described, as well as their functions and general patterns of their evolution. Techniques that underlie the description of proteins are discussed, including NMR, circular dichroism, optical rotatory dispersion spectroscopy, calorimetry,and crystallography. The book discusses the patterns of bochmical phenomena such as calcium homeostasis, mineralization, and cell signaling that involve specific proteins. It summarizes ongoing research and presents general hypotheses that help to focus future research, and also provides a conceptual framework and a description of the underlying techniques that permits someone entering the field to become conversant.

The hepatitis C virus (HCV) is a significant public health problem of international importance. HCV is capable of establishing chronic infections resulting in progressive liver damage and other problems. Current drug therapies are ineffective highlighting the need for better antiviral drugs. Recent research in HCV genetics and molecular biology have led to significant advances in our understanding of the life cycle of this important pathogen and may ultimately lead to better antiviral strategies. The editors of this book have recruited experts from around the world to produce a timely and well-compiled review of current HCV research with an emphasis on antiviral drug development. The chapters provide in-depth reviews of the most critical areas of research. Topics covered include: the HCV life cycle, HCV assays, HCV resources, HCV databases, HCV infection systems, models of hepatitis C infections, overview of the drug pipeline, clinical trial design, clinical virology and drug development, NS3 protease inhibitors, NS3-NS4A complex inhibitors, NS3 helicase inhibitors, NS4B targets and inhibitors, NS5A inhibitors, nucleoside inhibitors, NS5B polymerase inhibitors, glycoprotein-dependent entry, host cell targets and inhibitors, and innate immunity for HCV antiviral therapy. An essential book for scientists involved with HCV and anyone interested in antiviral drug development. A recommended text for all virology libraries.

This book covers important advances in enzymology, explaining the behavior of enzymes and how they can be utilized to develop novel drugs, synthesize known and novel compounds, and understand evolutionary processes. Advances in Enzymology focuses on enzymes, the primary catalysts of life processes. The explanation of the behavior of enzymes can be found via studies of their chemical mechanisms and can be utilized to develop novel drugs, synthesize known and novel compounds, and understand evolutionary processes. The transglutaminases, first described in 1957, are a large, widely-distributed family of enzymes canonically responsible for the amidation/transamidation of protein side chains. The extraordinary diversity of names associated with various enzymatic activities now recognized and aggregated as transglutaminase bears witness to the remarkable diversity of biological roles associated with the activity, including myriad human diseases.

Natural Killer Cells explains the importance of killer cells and how they are produced. It mentions that the most likely explanation for killer cell production is that they serve as a complementary system for T cells as a primary defense against viruses. However, these cells defend against certain viruses only, such as herpes viruses and influenza viruses. The book also explains the primary functions of killer cells, and it discusses how these cells help recognize damaged tissues, limit further damage to tissues, and regenerate damaged tissues. It discusses how these cells mature and develop, and it covers the different isolation, culture, and propagation methods of these cells. Furthermore, it focuses on the different killer cells that are present in various parts of the human body. The book concludes by explaining that natural killer cells are utilized for clinical therapy of malignancies, and that they have led to positive outcomes in the field of biology and medicine. - Provides a broad, detailed coverage of the biology and interactions of NK cells for students, fellows, scientists, and practitioners - Includes figures, histologic sections, and illustrations of the ontogeny of NK cells

By 2030, an estimated 47 million women will be undergoing menopause each year. With the progressive increase in life expectancy, the number of women older than 50, and consequently in menopause, is much higher today than in previous decades. In the United States, the average life expectancy for women is about eighty years, indicating not only a greater number of postmenopausal women but also that these women will live more than one third of their lives deprived of estrogen. The authors investigate the levels of the two important hormones, FSH and E2 during perimenopause. Levels of thyrotropin (TSH) in association with reproductive hormone are examined as well. Moreover, the physiopathogenesis of the sex- and menopause-associated differences in chronic liver disease are discussed, which are important to developing new approaches to prevention, diagnosis and treatment. The authors of this book also analyze the gender differences in the epidemiology, symptoms and progression of cardiovascular disease, which increases most markedly in women at the time of menopause. Furthermore, the management of the vasomotor symptoms, including hormonal replacement therapy (HRT) that constitutes the basis of the treatment of menopause symptoms are discussed.

Published since 1953, Advances in Virus Research covers a diverse range of in-depth reviews providing a valuable overview of the current field of virology. The impact factor for 2008 is 4.886, placing it 4th in the highly competitive category of virology. - Contributions from leading authorities - Informs and updates on all the latest developments in the field

Sex does matter. One of the most compelling reasons for understanding the biological differences, which are not so explained at this time, is that there are striking differences in human disease. The most obvious and best-studied differences between the sexes are in the reproductive systems. Much less study has been done on sex differences in non-reproductive areas of biology. Liver cancer is undoubtedly predominant in men and postmenopausal women. Almost anyone may “feel,” but not recognize the sex-associated difference in liver cancer as a fact. How does sex matter in the incidence of liver cancer? After considering the data and examples presented in this book, anyone will be provided unique opportunities to obtain a better understanding of differences of chronic liver disease between the sexes. Some of these differences can be explained by what we now know. Some are unexplained and point to important questions for future study. Being female or male is an important basic human variable that affects health and liver disease throughout the life span. A better understanding the biological mechanisms underlying the sex-associated differences in chronic liver disease would provide valuable information to design care of health and liver disease more effectively for individuals, both females and males.

Estrogens are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone. Estrogens are used as part of some oral contraceptives, in estrogen replacement therapy of postmenopausal women, and in hormone replacement therapy for transwomen. Like all steroid hormones, estrogens readily diffuse across the cell membrane; inside the cell, they interact with estrogen receptors. Additionally, estrogens have been shown to activate a G protein-coupled receptor. This new book gathers leading research from around the world.

Advances in Cancer Research provides invaluable information on the exciting and fast-moving field of cancer research. Here, once again, outstanding and original reviews are presented on a variety of topics, including nitric oxide-induced apoptosis in tumor cells, detection of minimal residual disease, immunity to oncogenetic human papillomavirus, and modeling prostate cancer in the mouse.

Rapid advances on molecular studies, manipulation of the mouse genome, the development of a number of animal models, and using these in studies of nonalcoholic fatty liver disease (NAFLD) have provided important insights into the pathogenesis of this relatively common disorder. One of the most crucial advances was to recognize the links among obesity, insulin resistance, inflammation and NAFLD. A growing body of literature has shown that insulin resistance and its liver-related consequence, NAFLD, could be the result of generalized inflammation. Genetic and behavioral factors contribute to increased visceral adipose tissue where increased oxidative stress and lipid peroxidation may contribute to dysregulated production of adipocytokines, fatty acids, and bioactive lipids. This chain of these events may contribute to local and peripheral insulin resistance, a central underlying pathophysiological process that may both cause and result from increased peripheral lipolysis and elevated free fatty acid concentrations in the circulation. Abnormally elevated free fatty acids taken up by organs other than adipose tissue, such as liver and skeletal muscle, contributes to steatosis of these organs (ectopic lipogenesis). Increased muscle and hepatocellular lipid content provides substrates for oxidative stress and lipid peroxidation, and also promotes insulin resistance in both liver and muscle by disturbing their downstream insulin signaling cascades. Insulin resistance further increases peripheral lipolysis in adipose tissue, further elevates circulating free fatty acids, inhibits hepatic fatty acid â-oxidation and increases de novo synthesis of both fatty acids and triglycerides in the liver. Excessively produced triglycerides in the liver are either stored as fat droplets or secreted into the plasma as very-low-density lipoproteins. If this complex mechanism of hepatic fat synthesis and secretion capacity is overwhelmed, excessive triglycerides accumulate within the hepatocytes and manifests as NAFLD. A fatty liver is sensitive to hepatocellular injury and sustained injury can manifest as nonalcoholic steatohepatitis (NASH), NASH-associated cirrhosis, and NASH-associated hepatocellular carcinoma. Specific depletion of hepatic natural killer T cells with consequent proinflammatory cytokine polarization of liver cytokine production might be one reason for this increased hepatic sensitivity against various stimuli. Only a minority of patients with NAFLD have the necroinflammatory changes of NASH. The development of NASH in patients with NAFLD may be the consequence of secondary abnormalities such as injured and dysfunctional mitochondria, generation of reactive oxygen species with down-regulation or consumption of antioxidants causing oxidative stress and lipid peroxidation, increased activity of cytochrome P450 2E1, disturbed production of adipocytokines, and the effects of gut-derived cytotoxic products. The dynamic interplay of these processes in the pathogenesis of NAFLD remains incompletely understood and is an area of active research.

The book discusses in detail new aspects of the metabolic basis of important chronic liver diseases. Entities such as non-alcoholic fatty liver disease (fatty liver and Non-Alcoholic SteatoHepatitis - NASH), diabeties in chronic hepetitis C, hemochromatosis, Wilson's disease, Gaucher disease, porphyria, as well as liver cirrhosis and its metabolic consequences will be discussed in detail. These clinical conditions are highly prevalent and affect millions of patients in the USA and worldwide. For example, non-alcoholic fatty liver disease is the most common cause of elevated liver enzymes in the general population. This field has been practically transformed over the last few years, with many new insights gained, regarding both pathogenesis and effective novel treatments.

Carrying on the high standards of the first edition of Differential Display Methods, Peng Liang et al. have based their second edition on a new mathematical model of differential display (DD) that takes advantage of automation, as well as digital data acquisition and analysis. These well-versed authors explain and highlight all the recent methodological refinements, including automated liquid handling of hundreds of DD PCR reaction setups combined with capillary electrophoresis, a prototype computer program to automatically allow positive band identification from a fluorescence differential display image, and restriction fragment-based DD screenings that can link any cDNA fragment directly to a given gene once the sequence information of all transcripts becomes available. Other improvements discussed are combining DD and DNA microarrays by reducing the complexity of cDNA probes while increasing the sensitivity of detection, and a DD approach to detect prokaryotic mRNA expression. The authors also demonstrate the power of DD technology with a collection of outstanding examples of DD applications and detailed experimental procedures. The elegant studies described here have led to the discovery of many important genes involved in viral infection, Prion disease, cancer, ovulation, circadian clock, floral color, transcription repression gene silencing, mRNA polymorphism, and protein-RNA interaction. State-of-the-art and highly practical, Differential Display Methods, Second Edition offers gene hunters the possibility of genome-wide comprehensive DD screening, as well as a proven road map for any successful'gene fishing'expedition

Despite the availability of an effective vaccine, there are still 400 million people worldwide who are chronically infected with the hepatitis B and D viruses (HBV and HDV), and more work still needs to be done in all of the key areas of managing the disease. In Hepatitis B and D Protocols, leading investigators and clinicians have joined forces to create a broad-ranging collection of core techniques for the study of HBV and HDV infections and for the development of therapies to treat them. In this first of two volumes Detection, Genotypes, and Characterization, the authors focus on readily reproducible molecular methods for the identification and quantification of viral markers, the detection and impact of viral variants, and the study of the viral life cycle. Each fully tested protocol is described in step-by-step detail by an established expert in the field and includes a background introduction outlining the principle underlying the technique, equipment and reagent lists, and tips on troubleshooting and avoiding known pitfalls. An accompanying second volume, Immunology, Model Systems, and Clinical Studies, contains user-friendly protocols for the study of host immune responses to infection, in vitro and in vivo models of infection, and the development of antivirals. Taken together, Hepatitis B and D Protocols, Volume 1: Detection, Genotypes, and Characterization and Volume 2: Immunology, Model Systems, and Clinical Studies offer both new and experienced investigators an encyclopedic collection of powerful tools for studying HBV and HDV infections, as well as an essential resource for finding new therapies to treat chronically infected patients.

Familiarity with nitric oxide is essential to a modern understanding of pathophysiologic mechanisms of infectious disease. Recent research has established nitric oxide and related reactive nitrogen intermediates to be important molecular mediators of diverse physiologic processes such as control of vascular tone, regulation of the immune system, and microbial and tumor cell growth. This book contains chapters by the leading researchers in the field and examines the biology and biochemistry of nitric oxide and its role in a variety of specific infections ranging from sepsis, tuberculosis and malaria to viral myocarditis, influenza, and AIDS.

Nitric oxide (NO) is a gas that transmits signals in an organism. Signal transmission by a gas that is produced by one cell and which penetrates through membranes and regulates the function of another cell represents an entirely new principle for signaling in biological systems. NO is a signal molecule of key importance for the cardiovascular system acting as a regulator of blood pressure and as a gatekeeper of blood flow to different organs. NO also exerts a series of other functions, such as acting a signal molecule in the nervous system and as a weapon against infections. NO is present in most living creatures and made by many different types of cells. NO research has led to new treatments for treating heart as well as lung diseases, shock, and impotence. Scientists are currently testing whether NO can be used to stop the growth of cancerous tumors, since the gas can induce programmed cell death, apoptosis. This book is the first comprehensive text on nitric oxide to cover all aspects--basic biology, chemistry, pathobiology, effects on various disease states, and therapeutic implications. - Edited by Nobel Laureate Louis J. Ignarro, editor of the Academic Press journal, Nitric Oxide - Authored by world experts on nitric oxide - Includes an overview of basic principles of biology and chemical biology - Covers principles of pathobiology, including the nervous system, cardiovascular function, pulmonary function, and immune defense