The imbalance between rapidly proliferating tumor cells and inadequate and inefficient tumor vasculature leads to a decrease in oxygen levels (hypoxia and/or anoxia) in tumor tissues. Intra-tumor hypoxia profoundly affects the biological behavior of cancer cells, which become resistant to conventional therapies and acquire a more invasive and metastatic phenotype.Hypoxia is a hallmark of the malignant phenotype and a key feature of the tumor microenvironment. Hypoxia Inducible Factor 1 (HIF-1) is a master regulator of the transcriptional response to oxygen deprivation.HIF triggers the expression of genes whose products induce angiogenesis, decrease oxygen consumption, switch metabolism to glycolysis, maintain a stem cell phenotype and select for more invasive and metastatic cells. Therapeutic approaches targeting HIF, directly or downstream mediators of its transcriptional activity, are being developed. Intra-tumor hypoxia is atopic hasbeen gaining scientific interestover the last few years for its wide involvement in many physiological and pathological processes.
This volume will cover the latest research and translational aspects associated with intra-tumor hypoxia, along with opportunities for drug development offered by this unique feature of the tumor microenvironment. The ongoing efforts to translate our understanding of the biology underlying intra-tumor hypoxia in viable therapeutic options face many challenges, but this book will provide an opportunity for an in-depth analysis of the fundamental mechanisms implicated in the adaption to low oxygen levels and will scrutinize the potential for opportunities that are being pursued in both research and the drug development industry."

Spanning from discoveries in fundamental immunology to industrial and commercial concerns, the study of vaccine adjuvants has developed into an exciting area of work with great, vital potential in innovating techniques in which adjuvants may steer the immune system towards the responses required by unmet vaccination needs. In Vaccine Adjuvants: Methods and Protocols, expert researchers in the field provide clear and concise guidance on how to go about assessing the activity of adjuvant products. Rather than describing individual adjuvants, the volume strives to include detailed, practical information on measuring the responses produced by adjuvants in order to be relevant to the widest array of experiments. Written in the highly successful Methods in Molecular Biology (TM) series format, 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 versatile, Vaccine Adjuvants: Methods and Protocols will enable those already pursuing vaccine adjuvant research, while also serving to stimulate discussion on how to best standardize adjuvant testing in order to facilitate meaningful comparisons, and above all, to aid in the prediction of which new products will most effectively and safely help to solve the current challenges in vaccination.

In this volume, the specific challenges and problems facing the evaluation of new oncology agents are explored with regards to pharmacokinetic, pharmacodynamic modeling and clinical pharmacology development strategies. This book delivers, with an emphasis on the oncology therapeutic area, the goals set in the first three volumes: namely - to provide clinical pharmacologists practical insights for the application of pharmacology, pharmacokinetics and pharmacodynamics for new drug development strategies. Pharmacokinetic-pharmacodynamic concepts for tyrosine kinases, the evaluation of cardiac repolarization prolongation through QTc interval effects, efficacy- and safety-response analyses to support new drug approvals, clinical and preclinical tumor growth modeling, and flat- vs weight-based dose selection are showcased from an oncology clinical pharmacologist's point-of-view. Oncology development strategies are surveyed for new FDA-approvals to identify patterns in expectations at time of first approval. The special considerations necessary to address combination drug development, metronomics, biosimilars and breakthrough therapies are also presented.

A concise, accessible account of pharmacology, covering all the key concepts you need with no gaps. It can be used either as an introduction to a topic, or as a revision aid. Big Picture Section - you can relate detail to the subject as a whole High Return Facts - fills large gaps in your knowledge. Can be used as a revision tool. Reinforces the major points Cartoon-strip illustrations - you can visualise difficult concepts in a step-by-step format - information is chunked into 'student-friendly' sizes Double-page overviews - read topic summaries without cross-referencing to other pages - they're all laid out in one spread!

Written by experts in the field, this comprehensive resource offers valuable information on the practical uses of drugs in primary eye care. Discussions of the pharmacology of ocular drugs such as anti-infective agents, anti-glaucoma drugs, and anti-allergy drugs lead to more in-depth information on ocular drugs used to treat a variety of disorders, including diseases of the eyelids, corneal diseases, ocular infections, and glaucoma. The book also covers ocular toxicology, focusing on drug interactions, ocular effects of systemic drugs, and life-threatening systemic emergencies. A logical organization makes it easy to find essential information. Complete coverage of the basic fundamentals of pharmacology such as ocular drug delivery and ocular drug formulations. Comprehensive reviews of the pharmacology of specific classes of agents such as the cycloplegics, antiglaucoma drugs, anti-inflammatory drugs, ocular irrigating solutions, and contact lens care products. In-depth information on ocular drugs used in clinical practice, including chapters on drugs used to treat eyelid disorders, lacrimal diseases, conjunctiva diseases, corneal diseases, allergies, uveitis, postoperative cataract, retinal diseases, and glaucoma. Coverage of ocular toxicology, including drug interactions, ocular effects of systemic drugs, and life-threatening systemic emergencies. Completely revised and updated content that reflects the latest advances in pharmacology. Updated information on post-operative drugs, including LASIK follow up medications. Expanded coverage in the chapters on Anti-infective Drugs, Anti-allergy Drugs and Decongestants, and Lubricants and Other Preparations of Ocular Surface Disease that includes the latest advancements in antibiotics and medications used to treat allergies and dry eye. A dosage quick reference guide on the inside front cover for quick and easy access. Information on the use of herbal medications.

Although it is one of the most-widely studied viruses, many mysteries still remain about HIV. Covering the latest advances and challenges associated with clinical application of new antiviral drugs and vaccines, this revised edition is a companion to Murad: "HIV-1: Molecular Biology and Pathogenesis, 2E." Leading investigators in HIV research present a timely picture of the molecular mechanisms which guide HIV-1 expression and replication and provide the most current clinical strategies for combating this virus.
* The latest developments in HIV-vaccine research
* New concepts in the discovery and design of novel anti-HIV drugs

This book covers research studies of aloe by the CAP (Creation Aloe Pharmaceuticals) team. It details the various physiological effects of those components for possible use as health foods or drugs. The team was organized into the isolation and analysis group, which purified many components in terms of low molecular weight compounds, carbohydrates, proteins present in aloe, and the assay group, which determined the efficacy of those components.

Sphingolipids are lipid components of the plasma membrane in eukaryotic cells. They have an important function in signaling mechanisms in the cell. This book on sphingolipids provides insights into the basics of sphingolipid biology and drug development, with a particular emphasis on the sphingolipid derivative ceramide. In the first part basic functions of sphingolipids are described, as well as the genetics of important enzymes, sphingolipid metabolism and synthesis. The second part of this first volume focuses on drug development and pharmacology. The book is intended for scientists in pharmacology, biochemistry and cell biology with a focus on biomedical research as well as for clinicians working in pharmacology, oncology, cardiology, neurology and infectious disease. Together with Volume 216 by the same editors, the collection represents a unique, comprehensive work on sphingolipids, providing information on both sphingolipids basic biology (including synthesis, metabolism and cell biology) and their important function in a (patho-)physiological context."

In this concise and systematic book, a team of experts select the most important, cutting-edge technologies used in drug delivery systems. They take into account significant drugs, new technologies such as nanoparticles, and therapeutic applications. The chapters present step-by-step laboratory protocols following the highly successful Methods in Molecular Biology(TM) series format, offering readily reproducible results vital for pharmaceutical physicians and scientists.

The book is oriented towards undergraduates science and engineering students; postgraduates and researchers pursuing the field of microbiology, biotechnology, chemical - biochemical engineering and pharmacy. Various applications of microorganisms have been covered broadly and have been appropriately reflected in depth in 12 different chapters. The book begins with an insight to the diverse niche of microorganisms which have been explored and exploited in development of various biotechnological products and green processes. Further, how these microorganisms have been genetically modified to improve the desired traits for achieving optimal production of microbially derived products is discussed in the second chapter. Major route of production of microbially derived products and processes is through fermentation technology and therefore due emphasis on different aspects of fermentation technology has been given in the subsequent chapter. The development and deployment of biopesticides and biofertilizers which find tremendous application have been separately discussed under agricultural applications. Application of microbes for the removal of pollutants, recovery of metals and oils has also been discussed under environmental applications. The role of microbial systems in development of fermented foods and beverages have also been discussed in Chapter 6. The application of microbes in production of commodity chemicals and fine chemicals has also been discussed in separate chapters. A chapter has been dedicated to the tremendous applications of microbially produced enzymes in different industrial sectors. Another unique facet of this book is explaining the different methods by which desired traits of microorganisms have been improved for their efficacious and economical exploitation in the industry. A chapter is dedicated to exploitation of microorganisms in development of vaccines for human and veterinary use. Finally, the last chapter discusses the role of immobilization in optimization of industrial processes and development of microbial biosensors for industrial applications. Thus, this book is a holistic approach providing information on the present applications of microorganisms.

The development of innovative drugs is becoming more difficult while relying on empirical approaches. This inspired all major pharmaceutical companies to pursue alternative model-based paradigms. The key question is: How to find innovative compounds and, subsequently, appropriate dosage regimens?

Written from the industry perspective and based on many years of experience, this book offers:

- Concepts for creation of drug-disease models, introduced and supplemented with extensive MATLAB programs

- Guidance for exploration and modification of these programs to enhance the understanding of key principles

- Usage of differential equations to pharmacokinetic, pharmacodynamic and (patho-) physiologic problems thereby acknowledging their dynamic nature

- A range of topics from single exponential decay to adaptive dosing, from single subject exploration to clinical trial simulation, and from empirical to mechanistic disease modeling.

Students with an undergraduate mathematical background or equivalent education, interest in life sciences and skills in a high-level programming language such as MATLAB, are encouraged to engage in model-based pharmaceutical research and development.

Muscarinic acetylcholine receptors have played a key role in the advancement of knowledge of pharmacology and neurotransmission since the inception of studies in these fields, and the effects of naturally occurring drugs acting on muscarinic receptors were known and exploited for both therapeutic and non-therapeutic purposes for hundreds of years before the existence of the receptors themselves was recognized. This volume presents a broad yet detailed review of current knowledge of muscarinic receptors that will be valuable both to long-time muscarinic investigators and to those new to the field. It describes the detailed insights that have been obtained on the structure, function, and cell biology of muscarinic receptors. This volume also describes physiological analyses of muscarinic receptors and their roles in regulating the function of the brain and of a variety of peripheral tissues. This volume shows how the study of muscarinic receptors continues to provide new and surprising insights not just to the cholinergic system but to the broad areas of neurobiology, cell biology, pharmacology, and therapeutics.

This volume covers the latest advances in the mechanisms of pathogenesis of the HIV-1 virus on target cells. Its companion volume, Advances in Pharmacology 56, shows how new developments in understanding the virus translate to the clinical setting.

Doping in sports and the fight against it has gained increasing attention in recent years. The pharmacological basis for a possible performance enhancement in competitive sport through the administration of prohibited substances and methods as well as the analytical disclosure of such practices are comprehensively covered in 21 contributions by outstanding and distinctive authors.

The extremely potent substance botulinum neurotoxin (BoNT) has attracted much interest in diverse fields. Originally identified as cause for the rare but deadly disease botulism, military and terrorist intended to misuse this sophisticated molecule as biological weapon. This caused its classification as select agent category A by the Centers for Diseases Control and Prevention and the listing in the Biological and Toxin Weapons Convention. Later, the civilian use of BoNT as long acting peripheral muscle relaxant has turned this molecule into an indispensable pharmaceutical world wide with annual revenues >$1.5 billion. Also basic scientists value the botulinum neurotoxin as molecular tool for dissecting mechanisms of exocytosis. This book will cover the most recent molecular details of botulinum neurotoxin, its mechanism of action as well as its detection and application.

This volume will address an important emergent area within the field of immunomics: the discovery of antigens and adjuvants within the context of reverse vaccinology. Conventional approaches to vaccine design and development requires pathogens to be cultivated in the laboratory and the immunogenic molecules within them to be identifiable. Conventional vaccinology is no longer universally successful, particularly for recalcitrant pathogens. By using genomic information we can study vaccine development in silico: 'reverse vaccinology', can identify candidate subunits vaccines by identifying antigenic proteins and by using equally rational approaches to identify novel immune response-enhancing adjuvants.

Chemical Drug Design provides a compact overview on recent advances in this rapidly developing field. With contributions on in silico drug design, natural product based compounds, as well as on ligand- and structure-based approaches, the authors present innovative methods and techniques for identifying and synthetically designing novel drugs.

This volume provides a comprehensive overview of the current issues facing scientists working on delivering drugs locally and systemically via the membranes that line the mouth. The book describes the anatomical and physiological challenges of this route for drug delivery and how they impact the design of oral mucosal drug delivery systems. It also provides a detailed description of current oral mucosal drug delivery technologies that overcome these challenges alongside research, development and assessment methods. In 11 authoritative chapters, the book affords an in-depth evaluation of the major issues associated with this route of administration, namely the retention of the drug/product at the site of administration and increasing drug permeability through the oral mucosa. The book provides insights into the in vitro and in vivo methods available to assess drug permeability and retention, offers solutions on how to improve the permeation of the drugs through the oral mucosa, and explores approaches to prolong drug/product retention at the site of administration. It also indicates future directions in research and product development. Oral Mucosal Drug Delivery and Therapy is a key resource for those wishing to extend their knowledge of this field.

Following the testing of therapeutic sera, the quantified evaluation of a pharmaceutical's efficacy became a key feature of medicine in the twentieth century. The case studies in this volume offer comparisons across Europe, from the diphtheria antitoxin in the late 1800s to the introduction of the Salk polio vaccine in the 1950s.

This is the first of three volumes in the "Ion Channels & Transporters in Tumor Biology" collection, which discusses the function of ion transport proteins in cellular and systemic homeostasis. The authors highlight the role of the so-called transportome, which is defined by the entirety of ion transporters and ion channels. Thereby, readers will get a better understanding of the impact dysregulated ion transport has on the whole spectrum of cancer types. Cancers display deficiencies in several, sometimes interdependent members of the transportome. Clinicians will be interested in the fact that controlled expression of ion transport proteins dramatically impacts the life span of cancer patients, as shown in recent studies. These observations offer a promising outlook for biomedical scientists, as members of the transportome could be the tumor markers of tomorrow - both for diagnostic and therapeutic purposes. As part of a three-volume collection, this book will fascinate members of the active research community, as well as clinicians from the cancer field.

This book seeks to unravel the mysteries of wolfberry, and systematically introduces its mechanisms in preventing aging-associated diseases, such as cardiovascular diseases, inflammation, liver and neurodegenerative diseases. Wolfberry, the dried fruit of Lycium barbarum, is an anti-aging herbal medicine. There have been numerous reports investigating the underlying mechanisms of its anti-aging effects and its role in preventing pathological changes in many aging-associated diseases. Its holistic effects on the body can attenuate liver toxicity and combat the spread of cancer; it also prevents degeneration in the central nervous system, and can even positively affect the skin. As such, wolfberry has become a very popular food supplement around the world. This book will serve as an excellent reference source for researchers and graduate students studying herbal medicine and aging-associated diseases, while also providing insights for the pharmaceutical industry with regard to developing potential drugs for these diseases.

The emergence of H5N1 avian influenza in 1997 and of the influenza A H1N1 of swine origin in 2009 calls for new, rapid and sustainable solutions for both seasonal and pandemic influenza viruses. During the last ten years, science and technology have made enormous progress, and we are now able to monitor in real time the genetics of viruses while they spread globally, to make more powerful vaccines using novel adjuvants, and to generate viruses in the laboratory using reverse genetics. This volume not only provides state-of-the-art information on the biology of influenza viruses and on influenza vaccines, but is also designed to be a resource to face the present H1N1 pandemic and to plan for long-term global and sustainable solutions.