This is the ideal book for anyone contemplating starting a career in, or shifting their career to, studying the dynamics that drive cancer progression and its response to therapy. Topics include the theory and population genetics of cancers, genetic diversity within tumors (intra-tumor heterogeneity), understanding how mutant clones expand in tissues, the role of cancer stem cells in the dynamics of tumors, the evolution of metastasis, and how to improve cancer therapy by addressing the evolution of cancers in response to our interventions. There are also chapters on the patterns of cancer susceptibility in humans due to a mismatch between our modern environment and the environment in which our ancestors evolved, as well as a chapter on the evolution of cancer suppression mechanisms that have evolved in different species, particularly the large long-lived animals like elephants and whales that are better at suppressing cancers than humans. This book serves as a primer on the evolutionary and ecological theory of cancer- the framework upon which all the details of cancer may be hung. It is ideal for oncologists and cancer researchers interested in evolutionary theory, and evolutionary biologists and ecologists interested in gaining insights into cancer development and prevention.

Following 50 years of glucocorticoid use in a clinical setting, an international body of expert scientists and physicians presents the most expansive survey of glucocorticoid pharmacology to date. This work traces the history of glucocorticoid biology from the seminal description of glucocorticoid insufficiency by Thomas Addison in the mid-19th century, up to current advances in elucidating the molecular basis of glucocorticoid action. Important discoveries are presented, as well as milestones in drug development, a survey of current clinical practice, and prospects for novel glucocorticoid-based therapeutics. Scientists and clinicians will appreciate the scope of this work, which is of special interest to workers in the fields of endocrinology, inflammation and autoimmune disease.

The chemistry of phenols tends to be ignored in organic chemical textbooks and to be lost amongst the many classes of functional derivatives. This volume is not intended to provide a textbook approach but rather to give an account of developments in phenol chemistry in the last two decades.

Features of this book:

- Numerous phenolic systems have been covered in detail, e.g. phenolic propanoids.

- The emphasis throughout has been on synthesis, on what can be achieved by the use of phenolic intermediates and in the construction of phenolic end products.

- Many chapters enable the reader to refer to the original literature wherever possible.

- Various chapters provide a fund of tutorial material and problems for undergraduate studies and further, which will encourage perusal of the literature. Some 2000 references to applied and academic papers are given.

Phenols are ubiquitous substances and now it is more widely accepted that there are pros and cons connected with their usage. The pros for compounds are well-known and are illustrated by perennial panaceas such as aspirin, paracetamol, codeine, etc. The cons are less obvious because they are also materials deeply entrenched in our standard of living and in most cases inherent hazards have only recently come to light. The book will be of interest to postgraduate students in academic and industrial work.

The book deals with various clinical aspects of cytochrome P450 2E1 (CYP2E1), which is a potent source for oxidative stress. Oxidative stress is critical for pathogenesis of diseases and CYP2E1 is a major contributor for oxidative stress. Several clinical disorders are associated with changes in regulation of CYP2E1 and the consequent abnormalities, which include alcoholic liver disease, alcoholic pancreatitis, carcinogenesis, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, obesity, hepatitis C virus infection, reproductive organ toxicity, hepatocellular and cholestatic liver cirrhosis, inhibition of bone repair, cross- tolerance in smokers and people treated with nicotine, disorders of the central nervous system, changes in metabolism of protoxicants in the circulatory system and susceptibility to human papillomavirus infection. Hence, CYP2E1 emerges as a new and potent player in aggravating injury and furthering disease complications.

In response to the tremendous increase in the number of protein and peptide drugs, this treatise critically reviews transport and metabolism mechanisms relating to the delivery of endogenous and recombinant proteins to mammalian organs, tissues, and cells. It will promote fruitful collaboration among academic and industrial scientists in the fields of pharmacology, cell biology, biochemistry, physiology, and immunology.

This fully updated volume utilizes the expertise of scientists currently engaged in immunotoxicity testing to provide the reader with lab-ready procedures and the background information needed to identify effective testing approaches. Dedicated to identifying and describing exogenous agents that can modify immune function, uncovering modes and mechanisms of action for such agents, and translating data from the laboratory and from the clinic to better predict health risks as well as benefits to those who are exposed to immunomodulatory agents, immunotoxicity testing continues to be a vital field of study, and this collection highlights both the "tried and true" methods as well as alternative protocols that have been more recently developed. Written in the highly successful Methods in Molecular Biology format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Immunotoxicity Testing: Methods and Protocols, Second Edition serves as a valuable contribution to the continued evolution and the application of immunotoxicity testing.

This volume gathers the latest exciting findings on ADP-ribosylation from renowned experts in the field. It includes ten chapters, organized into the following three thematic sections: * Evolution and detection of endogenous ADP-ribosylation * ADP-ribosylation by the ARTC family of ADP-ribosyltransferases (R-S-E ARTs) * ADP-ribosylation by the ARTD family of ADP-ribosyltransferases (H-Y-E ARTs) The book will provide readers a better understanding of ADP-ribosylating toxins and their endogenous relatives. This provides a basis for developing novel toxin-neutralizing drugs and drugs targeting endogenous ADP-ribosyltransferase relatives.

Fighting Multidrug Resistance with Herbal Extracts, Essential Oils and their Components offers scientists a single source aimed at fighting specific multidrug-resistant (MDR) microorganisms such as bacteria, protozoans, viruses and fungi using natural products. This essential reference discusses herbal extracts and essential oils used or under investigation to treat MDR infections, as well as those containing antimicrobial activity that could be of potential interest in future studies against MDR microorganisms. The need to combat multidrug-resistant microorganisms is an urgent one and this book provides important coverage of mechanism of action, the advantages and disadvantages of using herbal extracts, essential oils and their components and more to aid researchers in effective antimicrobial drug discovery

Addresses the need to develop safe and effective approaches to coping with resistance to all classes of antimicrobial drugs Provides readers with current evidence-based content aimed at using herbal extracts and essential oils in antimicrobial drug development Includes chapters devoted to the activity of herbal products against herpes, AIDS, tuberculosis, drug-resistant cancer cells and more "

This book provides multidisciplinary reviews of the mechanism of action and uses of methotrexate in the treatment of cancer, psoriasis, gynecologic and inflammatory diseases. The intended audience is composed of clinicians involved in the care of patients suffering from oncologic, gynecologic, rheumatic diseases as well as scientists involved in research into the pathogenesis and treatment of these diseases. This book is unique in that it provides a single, state-of-the-art source for information regarding the mechanism and use of methotrexate in many different areas of medicine.

This book provides a comprehensive review of both traditional and cutting-edge methodologies that are currently used in computational toxicology and specifically features its application in regulatory decision making. The authors from various government agencies such as FDA, NCATS and NIEHS industry, and academic institutes share their real-world experience and discuss most current practices in computational toxicology and potential applications in regulatory science. Among the topics covered are molecular modeling and molecular dynamics simulations, machine learning methods for toxicity analysis, network-based approaches for the assessment of drug toxicity and toxicogenomic analyses. Offering a valuable reference guide to computational toxicology and potential applications in regulatory science, this book will appeal to chemists, toxicologists, drug discovery and development researchers as well as to regulatory scientists, government reviewers and graduate students interested in this field.

The role that placebos play in many treatments is clear: they not only play a complimentary role in various treatment options but they can sometimes be the only beneficial option for treatment. Brain imaging studies over the past decade have shown that placebo-treated patients undergo some of the same changes in brain activity as those treated with pharmacologically active substances. Yet this important component of healing is not yet harnessed in clinical settings. The Placebo Effect in Clinical Practice brings together what we know about the mechanisms behind the placebo response, as well as the procedures that promote these responses, in order to provide a focused and concise overview on how current knowledge can be applied in treatment settings. An introductory chapter documents the ubiquity and extent of the placebo response and discusses the history of the placebo response in relation to medical treatment. Several subsequent chapters focus on how placebos work and how the placebo effect can be enhanced. Expectation, conditioning and elements of the treatment situation are covered in separate chapters. The relationship between psychotherapy and placebo treatment is covered as is the ethics of deliberate use of the placebo effect. Because placebo effects are particularly prominent in some psychiatric conditions, particular attention is given to the role of the placebo response in psychiatric treatment. The final chapter summarizes what we currently know and offers concrete suggestions for how what we know of the placebo effect can be used to enhance the benefit of all treatments.

Classical natural product chemistry is transitioning to modern day metabolomics as a result of the advent of comprehensive analytical platforms and sensitive analytical instrumentation. Therefore, it is worthwhile to summarize recent developments with current analytical platforms and highlight how metabolomics is being integrated into this classical field to dereplicate and profile natural product extracts. Metabolomics Tools for Natural Product Discoveries: Methods and Protocols aims to unite diverse and recently developed methodologies and protocols in order to identify bioactive secondary metabolites for the purpose of drug discovery. Some topics covered in this volume include applications for the extraction of selected natural products from less common sources such as bryophytes and hard corals, various biological assays, comprehensive applications and strategies for GC-MS, LC-MS, and NMR, as well as protocols and strategies for the structure elucidation of isolated natural products. Written in the successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible Metabolomics Tools for Natural Product Discoveries: Methods and Protocols seeks to serve both professionals and research students with its well-honed methodologies for natural product isolation, biomarker discovery, dereplication, biological assays, and comprehensive metabolomic platforms available for high-throughput analyses.

This book describes applications of acridines for the treatment of various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and various prion diseases, and discusses the potential of acridines in neuro-regenerative medicine. Using modern data-mining software, it presents structures of acridines with nucleic acids and proteins and compares them with the native structures. Furthermore, the book presents modern methods of acridine synthesis, comparing them with the most useful conventional methods. Acridines interact with both nucleic acids and proteins, and due to their direct interactions with various enzymes, they can be suitable for the treatment of neurodegenerative diseases, inflammation, immunological disorders, and protozoal diseases. The characteristic spectral properties of acridines can be employed in labeling proteins, nucleic acids, lipids, and even cells and their compartments. Moreover, they can be applied in photodynamic therapy.

This book highlights the importance of the choroid plexus, which forms the blood-cerebrospinal fluid barrier and is the site of the major production of the cerebrospinal fluid (CSF). The authors show that this barrier is crucial for maintaining important compositional differences between the blood plasma and the CSF. The choroid plexus epithelial cells also prevent the spread of infectious agents and other blood-borne entities to the brain tissue. Chapter topics range from the production of CSF by electrolyte regulation in the choroid plexus, to details on the selectively transporting nature of this barrier. Further, the authors elaborate on the important roles of CSF in sustaining brain health by providing hydration, solutes, and nutrients to the brain tissue. Readers will also learn how CSF circulates signaling molecules within the compartments of the brain and removes waste products from the brain tissue. Elucidating the regulation of these processes in the choroid plexus is not only important for the readers' understanding of normal brain development and function, but is also crucial for resolving a variety of cerebral challenges that lead to brain edema, as well as developing treatments for diseases. The book discusses disease models like hydrocephalus, sleep disorders, and age-related dementia. Its comprehensive coverage makes this volume a valuable resource for researchers in cell and neurophysiology, as well as graduate students of the neurosciences.

The environment is prone to suffer pollution and toxic insult from generations of nanomaterials as well from accidental releases during production, transportation, and disposal operations. The NMs could interact with and cause adverse biological effects at cellular, subcellular, and molecular levels. Assessing potential environmental/ecological risks requires quality information on transport and fate of nanoparticles in the environment, exposures and vulnerabilities of organisms to the nanomaterials and standard methods for assessing toxicity for aquatic or terrestrial organisms and human health. The systematic risk characterization and evaluation of the safety of nanomaterials require a multidisciplinary approach and convergence of knowledge and efforts from researchers and experts from toxicology, biotechnology, materials science, chemistry, physics, engineering, and other branches of life sciences. Although studies are beginning to appear in the literature addressing the toxicity of various nanomaterials and their potential for exposure, at this stage definitive statements regarding the impacts of nanomaterials on human health and the environment remain sketchy requiring an increased level of precautions with regard to nanomaterials, as has happened with other emerging contaminants and technologies (e.g., biotechnology). The need for an increased level of understanding the perception of risk and of benefits will vary and is likely to influence public, regulatory, and non-governmental activities regarding risk and benefit evaluations. Systematic identification and assessment of the risks posed by any new technology are essential. A prudent, integrated, and holistic approach is required to develop best practices based on the scientific understanding about what we know and what we don't know but need to know. Nanomaterials addresses key issues of ecotoxicological actions and effects of nanomaterials on life and environment, their threats, vulnerability, risks, and public perception. The readers learn to read bad news objectively and think about and search for ecological 'green' solutions to current environmental and ecological problems with blue, grey, brown, and red shades for building a sustainable ecosystem. It shows how this molecular terrain is a common ground for interdisciplinary research and education that will be an essential component of science, engineering and technology in the future. The book is divided into three sections. Section I includes general topics related to ecotoxicity of nanomaterials to microbes, plants, human and environment. Section 2 incorporates risks generated by the use of nanomaterials. Section 3 discusss safety issues and the public.

The field of oligonucleotide therapeutics research is ripe with the prospect of new discoveries. In "Therapeutic Oligonucleotides: Methods and Protocols," a selection of established and emerging methods for the application of oligonucleotides as therapeutics are presented, all providing the tools needed to inspire great changes in the field. Divided into twenty-one chapters, this detailed volume meticulously describes vital protocols for optimizing and improving cell uptake, such as photochemical internalization, modified cell penetrating peptides, antibody conjugates, and nanoparticles. Other chapters address quantitation of RNA therapeutics in cells, assaying gene knockdown, selecting the best target site and synthesis of various modified oligonucleotides. Written in the successful "Methods in Molecular Biology " series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls.

Authoritative and easily accessible, "Therapeutic Oligonucleotides: Methods and Protocols "serves as a timely resource for both professionals and novices pursuing research in this exciting and pioneering field."

Dendritic Cells; J.M. Austyn. The Multiple Accessory Cell Concept; M. Van Rooijen. Sythetic Peptides and the Role of T-Helper Cell Determinants; M.J. Francis. Carriers for Peptides; M.J. Francis. Co-Entrapment of T-Cell and B-Cell Peptides in Liposomes Overcomes Genetic Restriction in Mice and Induces Immunological Memory; G. Gregoriadis, et al. Preparation and Characterization of Stable Liposomal Hepatitis B Vaccine; D. Diminsky, et al. Initiation of Immune Response with ISCOM; B. Morein, et al. Nanoparticles as Potent Aduvants for Vaccines; J. Kreuter. Optimization of Carriers and Adjuvants; A. Snidjders, et al. Immunotargeting as an Adjuvant Independent Subunit Vaccine Design Option; D.L. Skea, B.H. Barber. BCG Vaccine; M.J. Groves, et al. Significance of Virulence Factors and ImmunoEvasion for the Design of Gene-Deleted Herpesvirus Marker Vaccines; S. Kit. Eradication of Sylvatic Rabies Using a Live Recombinant Vaccinia-vRabies Vaccine; M.P. Kieny, et al. 7 additional articles. Index.

This book was conceived from a simple question as to why cancer is so difficult to treat. Ultimately we want to find ways to cure cancers, but that may be an elusive dream at least with the technologies we have now and expect to have in the near future. This leads the question of whether it is possible to improve current cancer treatment methods, especially from the perspective of enhancing targeted drug delivery to tumors. This volume is designed to provide information related to the difficulties in treating cancers through targeted drug delivery, our current understanding of cancer biology, and potential technologies that might be used to achieve enhanced drug delivery to tumors. An ideal drug delivery system for treating cancers would maximize the therapeutic efficacy with minimal side effects in clinical applications. The seemingly improved anticancer efficacy of the current nanoparticle-based formulations needs to be viewed from the context of very poor success rates for translation to human applications. The results of in vitro cell culture models and small animal in vivo experiments have not been extrapolated to clinical applications. Finding the reasons for the lack of successful translation is required if we are to discover approaches to substantially extend the survival time of cancer patients, and hopefully identify cures. Cancer Targeted Drug Delivery: Elusive Dream describes some answers of achieving the so far elusive dream of treating cancers like other chronic diseases with therapies that focus using improved drug delivery systems designed to better align with the unique biological and physiological properties of cancer.

This book explores pain in a number of ways. At the heart of the book is an extension of Melzack's neuromatrix theory of pain into the social, cultural, and economic fields. Specific assemblages involving varied institutions, flows of capital, encounters, and social and economic structures provide a framework for the formation of pain, its perception, experience, meaning, and cultural production. Complementing the extended neuromatrix is a second theory, focussed on the propensity of western market capitalism to seek out new areas of life to subsume to capital. Pain is one such life area that is now ripe for exploitation. Although the book has theory at its heart, it draws extensively on case studies to identify the contradictions and complexities. Case studies are drawn from accounts of drug use in varied contexts such as prescription drugs, methamphetamine use, oxycodone use in North America, and the global rise of the medicinal cannabis marketplace.

This book addresses the highly relevant and complex subject of research on drugs from natural products, discussing the current hot topics in the field. It also provides a detailed overview of the strategies used to research and develop these drugs. Respected experts explore issues involved in the production chain and when looking for new medicinal agents, including aspects such as therapeutic potential, functional foods, ethnopharmacology, metabolomics, virtual screening and regulatory scenarios. Further, the book describes strategic methods of isolation and characterization of active principles, biological assays, biotechnology of plants, synthesis, clinical trials and the use of tools to identity active principles.

The action of antimicrobial peptides (AMPs), ranging from direct killing of invading pathogens to immune response modulation and other complex biological responses, has stimulated research and clinical interest for more than two decades, but the area is still burgeoning due to emerging discoveries in the functions, roles, and regulation of AMPs, thus making the study of antimicrobial peptides a multi-disciplinary and rapidly evolving field. In Antimicrobial Peptides: Methods and Protocols, leading investigators present a broad, up-to-date collection of current research and experimental methods for the isolation, characterization, production, and optimization of antimicrobial peptides. Additional chapters detail methodologies in several microscopy techniques, high-throughput screening, QSAR modeling, and computer-aided design used to study these compounds, while key review articles survey potential medical applications of antimicrobial peptides as innovative anti-infective and immunomodulatory agents, as well as emerging discoveries in their function, regulation, and roles in innate immunity. As a volume in the highly successful Methods in Molecular Biology (TM) series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and wide-ranging in its applications, Antimicrobial Peptides: Methods and Protocols provides both an authoritative guide for lab work on AMPs or related substances and a useful collection of thought stimuli to inspire further scientific endeavours in a wide array of vital fields.

Psychophysiology is an ever expanding field. The application of psychophysiological investigations to psychiatric disorders is likewise expanding and has in fact shed much light on some of the neural processes contributing to the development of psychiatric symptoms and/or their amelioration following treatment. In the first part of this volume, we have selected a number of conditions where psychophysiological investigations have recently provided some insight into the pathophysiology of a particular manifestation (e.g., dissociation) or a disorder. Although this volume has a main focus on electrophysiological investigative modalities where neuroimaging was complimentary this added insight was included. The second part of the volume focuses on novel uses of psychophysiological measures, combining it with neuropsychology and imaging where possible, in the context of neuropsychiatric research and describes advanced analytical tools. Both basic and clinical investigators in this field should find the reviews and interpretations provided clear and informative. Clinicians will find this volume easy to assimilate. While direct clinical applications may be down the road, the insights provided should help the practicing clinicians to have firmer understanding of the complexity of the disorder they manage in everyday practice.