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Environmental conditions and processes are one of the major pillars on which the human well-being rests. It is the core responsibility of the society to preserve and enhance better conditions for the human well-being. Indeed, there are several evolving unmet needs in public health. Emerging and re-emerging infectious diseases and a surge in the incidence of non-communicable diseases, including cardiovascular diseases (CAD), chronic respiratory diseases, and metabolic diseases have been impediments to sustainable well-being. Many factors are critical in the global surge in the rate and incidence of cardiovascular diseases. These include the shift from acute to chronic conditions, the shift from single risk factor vs. multiple influences, aging population, global health disparities, exposure to lower harmful influences over a longer period, etc. However, the epigenetic factors due to unhealthy environment play a most significant role in the underlying pathogenesis of cardiovascular diseases. Unfortunately, this has been ignored for a long time and realized lately to expand and disseminate knowledge to general population, expand research activities to investigate the cellular and molecular mechanisms, and develop better preventive and treatment strategies. The most significant environmental impoverishment in the pathogenesis of cardiovascular diseases include different genetical, chemical, physical, and biological influences, but not limited to, socio-economic status and lack of nutrients, nutritional aspects including habits, diets and additives, inhaled and ingested pollutants, exhaust gas and gasoline products, tobacco smoke, water pollution, alcohol consumption, soil and mineral pollution, solvents, pesticides, microplastics, non-critical usage of drugs, climate change, extreme atmospheric conditions, extremes in noise and temperature, electromagnetic influences, microwaves and radiation, outdoor light pollution, mental stressors, lack of or over exercise, microbiota and microbiological agents like SARS CoV-2 virus, etc.

This handbook provides comprehensive coverage of the application of proteases in cancer therapy. Proteases make up to two percent of the human genome and play a critical role in the tumor microenvironment. The book delves into the applications of natural, synthetic, and non-coding RNAs in cancer therapy. It highlights how effective targeting of relevant proteases can help in cancer diagnosis and treatment. It covers the systems biology and bioinformatics approach in cancer drug development. The book is meant for researchers and professionals in cancer research, biochemistry, and physiology.

For centuries, research has been conducted on the therapeutics of Brassicaceae plants and their health-promoting effects. Cato the Elder (234-149 BCE) documented their properties in his work De agri cultura and recommended using cabbage to compress wounds, swelling, burns, and bone dislocations. For arthritis, he recommended chopped raw cabbage mixed with coriander and cured cabbage mixed with vinegar and honey. In a groundbreaking discovery in the 1990s, scientists at Johns Hopkins University isolated sulforaphane from broccoli, revealing its potent anticancer properties. This naturally occurring compound has proven highly effective, safe, and tolerable and holds immense promise as a chemoprevention agent. It has the potential to combat various cancers, including breast, prostate, gastrointestinal, melanoma, lung, brain, and bladder. But its potential does not stop there. It also shows promise in treating cardiovascular and neurodegenerative diseases and diabetes, offering hope for those affected. The cancer-protecting properties of Brassica plants are mediated through compounds that induce a variety of physiological processes, including antioxidant action, detoxifying enzymes, inducing apoptosis, and cell cycle regulation. Glucosinolate breakdown products can affect several stages of cancer development, including the inhibition of activation enzymes (phase I) and the induction of detoxification enzymes (phase II). Isothiocyanates and indole products formed from glucosinolates regulate cancer cell development by regulating target enzymes, controlling apoptosis, inhibiting angiogenesis, metastasis, and the migration of cancer cells, and blocking the cell cycle. Sulforaphane, found in abundance in broccoli sprouts, plays a crucial role in upregulating the transcriptional activity of specific genes and restoring epigenetic alterations. This is particularly significant as it modifies epigenetic pathways by targeting histone deacetylases and DNA methyltransferases. These modifications, in turn, alter gene transcription and expression, particularly in the case of cancers. This intricate process of gene regulation is a fascinating study area, making broccoli sprouts a compelling component of the'epigenetic diet.'Sulforaphane induces the cytoprotective enzyme NQO1. The inducible expression of NQO1 is regulated principally through the Keap1-Nrf2-ARE signaling pathway. The activation of the Nrf2-Keap1 signaling pathway heralds the beneficial actions of drugs known to affect Nrf2 signaling, such as dimethyl fumarate, an FDA-approved treatment for multiple sclerosis, and bardoxolone methyl for chronic kidney disease. There is optimism that the overall strategies are moving forward. Sulforaphane-rich broccoli sprout extracts provide one avenue toward this end.

TRP Channels as Therapeutic Targets, Second Edition is a comprehensive reference on the roles of TRP Channels in health and disease states. The Editor lined up a team of worldwide experts in academia and corporate R&D to provide diverse views into these promising drug development targets. Following the research development happened in the past ten years, since the first edition published, the revision includes seven new chapters. All remaining chapters are completely updated. New topics included in the book are TRP channels biology, the crystalline structure of TRP channels, targeting TRP channels for pain relief, the relationship with migraine, emerging pain targets, a comprehensive view of the role of TRP channels in respiratory diseases and COVID complications, anxiety relief, renal disease, arthritis, and therapeutic opportunities for thermal regulation. TRP Channels as Therapeutic Targets, Second Edition is a reference for broad segments of the scientific and medical community. Researchers working on TRP channel drug discovery will benefit from the overview of applications to conditions in specific organ systems. Clinicians interested in new drugs in the pipeline, will find in this book their biologic principles of action. - Presents the perspectives of several life science research specialties on the topic - Provides a comprehensive picture of the TRP field, from TRP channel dysfunction through TRP drug discovery and development to clinical trials and everyday medical practice - Represents an updated and complete reference

Effective drug delivery systems are essential in maximizing the therapeutic effects of the drugs in question. This book thoroughly analyses recent technological advances in new, nanomaterial-based drug delivery systems for the diagnosis and treatment of various diseases. These systems also have diverse applications in pharmaceutical, biomedical, biomaterial, and biotechnological fields. This book explains the different types of nanocarriers currently in development and covers both therapeutic and theranostic applications of drug-loaded nanocarriers and nanomedicine.Clinical research professionals, industrial pharmaceutical scientists, and veteran drug delivery developers benefit from the unique structure of this book, making it essential for the drug delivery researcher. Students, research scholars, and industrial professionals alike benefit from the current technological advancements, regulatory aspects, and the history of discovery and development in the field of nanomedicine presented in this book.

Steroids are an important class of biomolecules with diverse roles and functions. Besides being important as structural and signaling molecules, these molecules hold promise against numerous disorders, including cardiovascular conditions, cancer, inflammation and autoimmune disorders. Many investigations have demonstrated that steroidal frameworks may provide lipid solubility, receptor selectivity or membrane binding properties to non-steroidal pharmacophores. However, the therapeutic use of steroids can be dangerous when they're used incorrectly. Additionally, misconceptions about steroids among athletes or recreational users can lead to steroid abuse and poor health outcomes.Steroids and their Medicinal Potential discusses the classification, distribution, biosynthesis, chemical synthesis and semi-synthesis of different steroids. The medicinal potential of each class is exhaustively discussed in different chapters. The latest advances and developments in steroid-based drug discovery are also discussed thoroughly. The book aims to address general questions and concerns about steroids, providing readers a useful resource on the subject.Key Features-Provides comprehensive coverage on all aspects of steroids including steroid chemistry, biochemistry, medicinal potential, drug discovery and advances in target-binding interactions of steroid-based drugs-Includes chapters dedicated to anabolic steroids and their abuse-Designed as an accessible source of information for understanding steroidal drugs with structured chapters-Includes references for advanced readers

Advanced Porous Biomaterials for Drug Delivery Applications probes cutting-edge progress in the application of advanced porous biomaterials in drug delivery fields. These biomaterials offer promise in improving upon the design, cost, and creation of potent novel drug delivery systems. The book focuses on two categories: nature engineered and synthetic advanced porous biomaterials, with a wide range of low-cost porous biomaterial-based systems that have been used for the delivery of diverse drugs through in vitro/in vivo approaches. Details how advanced porous biomaterial-assisted systems improve essential properties in drug delivery applications Explains how advanced porous biomaterials systems are being used and explored to improve overall performances of drug delivery systems in mitigating a variety of diseases Emphasizes major applications in drug delivery such as controlled release, cancer therapy, and targeted delivery, and with focus on oral, topical, and transdermal applications Focuses on both naturally available and synthetic low-cost advanced porous biomaterials and their role in enhancing important parameters in drug delivery applications Accessible to readers with bio and non-bio backgrounds This book is an ideal reference for academics, researchers, and industry professionals in the interdisciplinary fields of biomedicine and biomedical engineering, pharmaceuticals, materials science, and chemistry.

By examining historical applications of the compounds found in plants, this five-volume series serves as a reference for quality assurance, research, product development, and regulatory guidance of the compounds found in plant-based medicines. This work supports the growing consumers'interest in herbal medicine for wellness and health. Plant-Based Therapeutics, Volume 1: Cannabis sativa, the first in the series, covers a unique plant species and provides the framework to integrate its evidence-based scientific discoveries with healthcare therapies. Cannabis has been used in religious ceremonies and medical purposes for thousands of years. Cannabidiol (CBD), the main non-psychoactive component of Cannabis, was isolated in the 1940s, and its structure was established in the 1960s. In 1964 tetrahydrocannabinol (THC), the psychoactive component, was isolated. Cannabis has more than 500 components, of which 104 cannabinoids have been identified. Two of them, THC and CBD, have been the primary components of scientific investigations. They were approved by the FDA for chemotherapy-induced nausea and vomiting in 1985; for appetite stimulation in wasting conditions, such as AIDS, in 1992, and in 2018 for treating two forms of pediatric epilepsy, Dravet syndrome and Lennox-Gastaut syndrome. Beyond the indications for which cannabinoids are FDA-approved, the evidence reveals that cannabinoid receptors are present throughout the body, embedded in cell membranes, and are believed to be more numerous than any other receptor system. When cannabinoid receptors are stimulated, a variety of physiologic processes ensue. Thus, other constituents of Cannabis are extremely promising either as individual compounds or their potential synergistic or entourage effects in the treatment of numerous medical conditions.

This third edition of Medicinal Chemistry of Anticancer Drugs, provides an updated resource for students and researchers from the point of view of medicinal chemistry and drug design, focusing on the mechanism of action of antitumor drugs from the molecular level, and on the relationship between chemical structure and chemical and biochemical reactivity of antitumor agents. Antitumor chemotherapy is a very active field of research, and a huge amount of information on the topic is generated every year. This new edition includes updated sections on the hot topic of cancer immunotherapy, cancer polypharmacology, multitargeted cancer therapy, medicinal chemistry of cancer diagnosis, theranostic anticancer agents, and pre-mRNA processing in cancer. Although many books are available that deal with clinical aspects of cancer chemotherapy, this book provides a unique and valuable perspective from the point of view of medicinal chemistry and drug design. It will be useful to undergraduate and postgraduate students of medicinal chemistry, pharmacology, biological chemistry, pharmacy and other health sciences. Researchers and practitioners will find a comprehensive treatment of the topic and a large number of references to reviews and the primary literature. - Provides a resource that is organized consistently based on targets and mechanisms of action from a molecular point-of-view - Focuses on the relationship between chemical structure and chemical and biochemical reactivity of antitumor agents, providing a rationalization on the action of these type of drugs and the design of new active structures - Features a large number of color figures which give information in a clear-and-concise way - Includes extensive references to review articles and primary literature - Includes updated sections on the hot topic of cancer immunotherapy, cancer polypharmacology, multitargeted cancer therapy, medicinal chemistry of cancer diagnosis, theragnostic anticancer agents, and pre-mRNA processing in cancer

This book addresses various aspects of recent progress in the development of all types of tumorresponsive and site-specific delivery platforms together with the range of related chemistries. It is a timely volume as global research in oncology is moving towards more biochemical signal–based and cell environment–inspired therapeutic strategies. Furthermore, the book emphasizes the need to explore various characterization techniques for specific stimuli-responsive nanoplatforms and toxicological and regulatory aspects.Features: Focused, comprehensive volume providing a different angle on theranostics in cancer intervention Targets not only the multifunctionality of nanosystems but provides a comprehensive overview of niche technical aspects Given the chemistries presented here, it provides both early-career and experienced readers with strategies from leading authorities in the field globally

This book gives an overview of therapeutic drug monitoring (TDM) and its clinical application. It also highlights recent advances in toxicological studies, as they relate to therapeutic drug monitoring. This is one of the few books available on the market that covers TDM. Therapeutic drug monitoring (TDM) is a clinical decision-making tool that enables dosage regimen adjustments based on clinical and laboratory measurements. TDM not only involves the measuring of drug concentrations but also interpretation of the results. There is a strong correlation between drug concentrations in body fluids and outcome than between dose and outcome. The chapters include coverage of analytical techniques, pharmacokinetics, therapeutic indices, artificial intelligence and recent advances in toxicological studies.The book fills a gap in published literature and provides reliable information on; Analytical techniques in TDM and clinical toxicology TDM and pharmacokinetic studies TDM of drugs with narrow therapeutic indices Artificial intelligence in TDM and clinical toxicology Future directions and challenges

Cancer will remain a global major health problem unless new diagnostic, prognostic, and management approaches are discovered to address both loss of life and quality of life. Here we summarize the general physiology, pathology, heterogeneity, and evolution of cancer, current status, limitations and challenges associated with prevention, incidence, treatment, survival, and mortality, as well as future directions with regards to solid tumors. Perspectives are provided on how to improve pre-clinical understandings, outcomes, and patient care. Further, this comprehensive, timely overview of the literature has educational value as part of an academic course, seminar, or as a supplementary text.Features : This book summarizes the current status, successes, difficulties, advancements, limitations, and challenges in medical interventions that impact patients'quality of life. Includes concise descriptions of all relevant cell and molecular biology concepts including evolutionary paradigms, hallmarks of cancer, and heterogeneity to help understand the pathophysiology of cancer, cancer-associated disease conditions, and effective cancer therapy. Contains an array of colorful figures and schematics summarizing complex informative pathological, physiological, and biochemical concepts. Covers a multitude of sub-topics pertaining to cancer biology including diagnosis; chemotherapy, radiotherapy and targeted therapy; metastasis; disseminated and circulating tumor cells, and cancer stem cells; drug resistance and cellular reprogramming; complex epigenetics; tumor-derived exosomes; oncogenic viruses; metabolic syndrome and cancer metabolism; convoluted neovascularization; efficient biomarkers; immunotherapy; role of nutraceuticals and natural products. Provides perspectives on how to improve pre-clinical understandings, and outcomes, linking toxicological, and pharmacological aspects in patient care. This timely, relevant comprehensive assortment of scientific literature has educational value to a wider audience including as part of an academic course, seminar, or as a supplementary text.

Frontiers in Natural Product Chemistry is a book series devoted to publishing monographs that highlight important advances in natural product chemistry. The series covers all aspects of research in the chemistry and biochemistry of naturally occurring compounds, including research on natural substances derived from plants, microbes and animals. Reviews of structure elucidation, biological activity, organic and experimental synthesis of natural products as well as developments of new methods are also included in the series.Volume nine of the series brings together 7 reviews on a variety of natural products and sources along with a chapter on the basics of investigating antioxidant activity.Propolis and its key chemical constituents: a promising natural product in therapeutic applicationsInvestigation of the effects of using omega-3 fatty acids on egg quality in functional egg productionQuercetin, a flavonoid with remarkable anticancer activitySwertiamarin for the treatment of metabolic syndromeOverview of traditional uses, phytochemistry and pharmacology of Peganum harmala l.Investigation of measurement methods of antioxidant activity and involved mechanismsRecent progress on natural and synthetic flavanone and its derivativesRole of virgin coconut oil as a multiple health promoting functional oil

Phytoantioxidants and Nanotherapeutics Discover the medicinal importance of antioxidant herbal medicines, phytochemicals, and nanodelivery systems for a wide range of diseases Phytomedicine has been—and continues to be—central to many cultures and societies due to its low toxicity, low cost, accessibility, and efficacy in treating difficult diseases. In fact, many plant-derived bioactive natural products serve as potential sources of drug leads or therapeutic agents in the treatment of a wide range of human diseases. When combined with nanotechnology, phytomedicine has the potential to affect and impact a tissue-specific site, which can reduce drug dosage and side effects while improving activity. Phytoantioxidants and Nanotherapeutics offers a comprehensive look at the significant role that phytomedicine-derived antioxidants play on the field of medicine, particularly when combined with the nanotechnology-derived drug delivery systems. The book thoroughly covers the herbs, plant extracts, and other dietary elements that may be used as sources of natural antioxidants and similarly highlights the use of phytomedicine- derived bioactive compounds including plant polyphenols and flavonoids to reducing the impact of oxidative stress induced human diseases. The text also demonstrates the biochemical and therapeutic targets of nanodrugs and discusses nanostructure toxicity, while emphasizing the challenges and regulatory issues involved with nanophytotherapeutics. Phytoantioxidants and Nanotherapeutics readers will also find: A helpful bridge between the cutting-edge field of nanotechnology delivery and phytotherapeutics The potential role of bioactive phytochemicals, particularly polyphenolic compounds and flavonoids, in oxidative stress-induced diseases Description of the latest developments on nanotherapeutics of phytoantioxidants for the treatment of certain chronic human diseases, such as cancer, inflammations, diabetes, viral, bacterial and parasitic infections, nervous system disorders, cardiovascular disorders, and neurological diseases. Phytoantioxidants and Nanotherapeutics is a useful reference for drug manufacturers and drug developers, formulation scientists, biomedical scientists, medicinal chemists, phytochemists, healthcare providers, and academics and researchers.

A decade after publication of the first edition, Handbook of Venoms and Toxins of Reptiles responds to extensive changes in the field of toxinology to endure as the most comprehensive review of reptile venoms on the market. The six sections of this new edition, which has nearly doubled in size, complement the original handbook by presenting current information from many of the leading researchers and physicians in toxinology, with topics ranging from functional morphology, evolution and ecology to crystallography, -omics technologies, drug discovery and more. With the recent recognition by the World Health Organization of snakebite as a neglected tropical disease, the section on snakebite has been expanded and includes several chapters dealing with the problem broadly and with new technologies and the promises these new approaches may hold to counter the deleterious effects of envenomation.This greatly expanded handbook offers a unique resource for biologists, biochemists, toxicologists, physicians, clinicians, and epidemiologists, as well as informed laypersons interested in the biology of venomous reptiles, the biochemistry and molecular biology of venoms, and the effects and treatment of human envenomation.

Protein phosphorylation via protein kinases is an inevitable process that alters physiological and pathological functions of the cells. Thus, protein kinases play key roles in the regulation of cell life or death decisions. Protein kinases are frequently a driving factor in a variety of human diseases including aging and cellular senescence, immune system and endothelial dysfunctions, cancers, insulin resistance, cholestasis and neurodegenerative diseases, as well as bacterial resistance in persistent infections. Recent developments in quantitative proteomics provide important opinions on kinase inhibitor selectivity and their modes of action in the biological context. Protein Kinase-mediated Decisions Between Life and Death aims to have the reader catch insights about up-to-date opinions on “Protein Kinases” related pathways that threaten human health and life. As “Protein Kinases” are related to many health problems, clinicians, basic science researchers and students need this information.Chapter “Signal Transduction in Immune Cells and Protein Kinases” is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

We have surpassed the omics era and are truly in the Age of Molecular Therapeutics. The fast-paced development of SARS-CoV-2 vaccines, such as the mRNA vaccines encoding the viral spike protein, demonstrated the need for and capability of molecular therapy and nanotechnology-based solutions for drug delivery. In record speed, the SARS-CoV-2 viral RNA genome was sequenced and shared with the scientific community, allowing the rapid design of molecular therapeutics. The mRNA vaccines exploit the host cell endoplasmic reticulum to produce viral spike proteins for antigen presentation and recognition by the innate and adaptive immune system. Lipid nanoparticles enable the delivery of the fragile, degradation-sensitive nucleic acid payloads. Molecular-based therapeutics and nanotechnology solutions continue to drive the scientific and medical response to the COVID-19 pandemic as new mRNA, DNA, and protein-based vaccines are developed and approved and the emergency use approved vaccines are rapidly manufactured and distributed throughout the globe. The need for molecular therapies and drug delivery solutions is clear, and as these therapies progress and become more specialized there will be important advancements in organelle targeting. For example, using organelle targeting to direct lipid nanoparticles with mRNA payloads to the endoplasmic reticulum would increase the efficacy of mRNA vaccines, reducing the required dose and therefore the biomanufacturing demand. Likewise, improving the delivery of DNA therapeutics to the nucleus would improve efficacy. Organelles and molecules have always been drug targets, but until recently we have not had the tools or capability to design and develop such highly specific therapeutics. Organelle targeting has far-reaching implications. For example, mitochondria are central to both energy production and intrinsic apoptosis. Effectively targeting and manipulating mitochondria has therapeutic applications for diseases such as myopathies, cancer, neurodegeneration, progerias, diabetes, and the natural aging process. The SARS-CoV-2 vaccines that exploit the endoplasmic reticulum (for mRNA vaccines) and the nucleic translational process (DNA vaccines) attest to the need for organelle and molecular therapeutics. This book covers the status, demand, and future of organelle- and molecularly targeted therapeutics that are critical to the advancement of modern medicine. Organelle and molecular targeting is the drug design and drug delivery approach of today and the future; understanding this approach is essential for students, scientists, and clinicians contributing to modern medicine.

Clinical Perspectives and Targeted Therapies in Apoptosis: Drug Discovery, Drug Delivery, and Disease Prevention provides comprehensive coverage, from basic cell biology, to modern assessment techniques for apoptosis in all major disease areas. Chapters provide an introduction to the fundamentals of cell biology, biochemical mechanisms, and the pathophysiological consequences of apoptosis. In addition, the book covers the tools and techniques used to quantify apoptosis and the significance of apoptosis in drug discovery, drug delivery, and its applications in disease prevention. Finally, the book provides a comprehensive compilation of the apoptosis targeting drugs that recently underwent clinical trials. This combination of fundamentals, along with applications in drug discovery, drug delivery, and clinical research make this book a useful resource for those in both academia and industry who are engaged in pharmaceutical, biomedical and biotechnology research. - Offers standard and innovative therapeutic approaches to modulate apoptosis in clinical interventions, such as cardiovascular diseases, immune disorders, cancer chemotherapy and neurological ailments - Covers cutting-edge laboratory techniques and traditional protocols to determine apoptosis, both in vitro and in vivo - Examines clinical study reports of new drug moieties that are explored for various pathological conditions associated with apoptosis

This book consists of 3 volumes: Basic Science (Volume 1), Clinical Science (Volume 2) and Technology and Methodology (Volume 3). Volume 2 focuses on the clinical aspects of autophagy research, discussing the role of autophagy in neuropsychiatric disorders, the cardiovascular, immune, digestive and endocrine systems, as well as tumors, infection, the kidney, and the respiratory and hematological systems. It also addresses autophagy-related drug development. Written and edited by a team of 90 experts, and presenting the state of the art in autophagy research, this book is a valuable reference resource for researchers and clinicians alike. It can also be used as supplementary material for graduate students majoring in biology and medicine

Presenting both a panoramic introduction to the essential disciplines of drug discovery for novice medicinal chemists as well as a useful reference for veteran drug hunters, this book summarizes the state-of-the-art of medicinal chemistry. It covers key drug targets including enzymes, receptors, and ion channels, and hit and lead discovery. The book hen surveys a drug's pharmacokinetics and toxicity, with a solid chapter covering fundamental bioisosteres as a guide to structure-activity relationship investigations.

In this book, a summary and update of the most important areas of cell-penetrating peptides (CPP) research are presented, while raising relevant questions for further development. The CPP sequences are presented and discussed throughout the book. The methods for testing CPP mechanisms are discussed in detail. Various approaches for the testing of endocytotic pathways of CPP uptake are also described. Different CPP uptake experiments are compared since it is becoming clear that it is often best to apply several methods in a complementary manner in order to most comprehensively evaluate CPP uptake mechanisms due to the complexity of these processes. A brief summary of functionality issues of CPPs, both in vitro and in vivo, is discussed. Therapeutic potential of CPPs and commercial developments are discussed. The present, second edition of this book is the updated and expanded version of the first edition, published in 2019. The development of the field of cell-penetrating peptides in these five years has been obvious and exciting. This second edition of the book has been partly reorganized and comprehensively expanded with the exciting research in 2019-2023. Around 2500 novel scientific articles have become available, most of them are reviewed in the second edition. Additional rapidly growing areas of high impact presented in this second edition are therapeutic developments (Chapter 16) and delivery of oligonucleotides and proteins/peptides (Chapters 5 and 6) including novel reports on genome editing with CPP assistance. Also, several additional examples are available now on clinical trials using CPPs (Chapter 15). The book is written for researchers and students in the field.

Frontiers in Anti-Cancer Drug Discovery is a book series devoted to publishing the latest advances in anti-cancer drug design and discovery. In each volume, eminent scientists contribute reviews relevant to all areas of rational drug design and drug discovery including medicinal chemistry,in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, recent important patents, and structure-activity relationships. The book series should prove to be of interest to all pharmaceutical scientists involved in research in anti-cancer drug design and discovery. The book series is essential reading to all scientists involved in drug design and discovery who wish to keep abreast of rapid and important developments in the field. The tenth volume of the series features chapters covering the following topics: - Challenges in the Management of Hepatoblastoma - The Emerging Role of Monocarboxylate Transporter-1 in Cancer - In-vitro Anti-Proliferative Assays and Techniques Used in Pre-Clinical Anti-Cancer Drug Discovery - Recent Advances in the Development of Mesoporous Anti-Cancer Drug Nanocarriers - Polyphenols and Cancer - Glioblastoma Multiforme - Cutting Edge Targeting Strategies Utilizing Nanotechnology in Breast Cancer Therapy

Choice Recommended Title, April 2020This comprehensive book, edited by two leading experts in nanotechnology and bioengineering with contributions from a global team of specialists, provides a detailed overview of the environmental and health impacts associated with the toxicology of nanomaterials.Special attention is given to nanomaterial toxicity during synthesis, production and application, and chapters throughout are focused on key areas that are important for future research and development of nanomaterials. This book will be of interest to advanced students studying biomedical engineering and materials science, PhD researchers, post-docs and academics working in the area of nanotechnology, medicine, manufacturing and regulatory bodies.Features: Collates and critically evaluates various aspects of the toxicology of nanomaterials in one comprehensive text Discusses the various effects of nanocrystals including the morphologies on cytotoxicity, in addition to the environmental and cytotoxicity risks of graphene and 2D nanomaterials Explores practical methods of detection and quantification, with applications in the environmental and healthcare fields

The application of drug delivery is a valuable, cost-effective lifecycle management resource. By endowing drugs with new and innovative therapeutic benefits, drug delivery systems extend products'profitable lifecycle, giving pharmaceutical companies competitive and financial advantages, and providing patients with improved medications. Formulation development is now being used to create new dosage forms for existing products, which not only reduces the time and expense involved in new drug development, but also helps with regard to patent protection and bypassing existing patents. Today's culture demands convenience, a major factor determining adherence to drug therapy. Over the past few years, patient convenience-oriented research in the field of drug delivery has yielded a range of innovative drug-delivery options. As a result, various drug-delivery systems, including medicated chewing gums, oral dispersible tablets, medicated lozenges and lollipops, have now hit the marketand are very popular. These dosage forms offer a highly convenient way to dose medications, not only for special population groups with swallowing difficulties, such as children and the elderly, but for the general populace as well. This book provides valuable insights into a number of formulation design approaches that are currently being used, or could be used, to provide new benefits from existing drug molecules.

Publisher's Note: Products purchased from Third Party sellers are not guaranteed by the publisher for quality, authenticity, or access to any online entitlements included with the product. Toxicology's gold-standard text - completely updated to reflect the latest breakthroughs and discoveries A Doody's Core Title for 2019! Casarett & Doull's Toxicology: The Basic Science of Poisons, Ninth Edition equips you with an unsurpassed understanding of modern toxicology, including the key principles, concepts, mechanisms, chemical-specific toxicity, and modes of thought that are the foundation of the discipline. This trusted classic not only delivers a comprehensive review of the essential components of toxicology, it offers the most up-to-date, revealing, and in-depth look at the systemic responses of toxic substance available anywhere. Casarett & Doull's Toxicology: The Basic Science of Poisons, Ninth Edition is logically divided into seven sections: •General Principles of Toxicology •Disposition of Toxicants •Non-Organ Directed Toxicity •Target Organ Toxicity •Toxic Agents •Environmental Toxicology •Applications of Toxicology Many new contributors capture the progress made in toxicology over the past few years: This edition is markedly updated from the previous edition, with more than one-third of the chapters authored by scientists who have not made previous contributions to the book. Sharing their expertise, they deliver dynamic new coverage of the importance of apoptosis, autophagy, cytokines, growth factors, oncogenes, cell cycling, receptors, gene regulation, protective mechanisms, repair mechanisms, transcription factors, signaling pathways, transgenic mice, knock-out mice, humanized mice, polymorphisms, microarray technology, second-generation sequencing, genomics, proteomics, epigenetics, exposome, microbiota, read across, adverse outcome pathways, high-content screening, computational toxicology, innovative test methods, and organ-on-a-chip in understanding the mechanisms of toxicity and the regulation of chemicals. A true “essential” If you are in need of an up-to-date, all-in-one overview of the biomedical and environmental aspects of toxicology - written by experts, and presented in full color, your search ends here.

Volume 18, entitled Metallo-Drugs: Development and Action of Anticancer Agents of the series Metal Ions in Life Sciences centers on biological, medicinal inorganic chemistry. The serendipitous discovery of the antitumor activity of cis-diamminodichloroplatinum(II) (cisplatin) by Barnett Rosenberg in the 1960s is a landmark in metallodrug-based chemotherapy. The success of cisplatin in the clinic, followed by oxaliplatin and carboplatin, along with their drawbacks relating mainly to resistance development and severe toxicity, initiated research on polynuclear platinum complexes and on Pt(IV) complexes as prodrugs. Furthermore, the indicated shortcomings led to the exploration of other transition and main group metal ions, among them Ru(II/III), Au(I/III), Ti(IV), V(IV/V), and Ga(III) including also the essential metal ions Fe(II/III), Cu(I/II), and Zn(II). Ionic as well as covalent and non-covalent interactions between structurally very different complexes and biomolecules like nucleic acids, proteins, and carbohydrates are studied and discussed with regard to their possible anticancer actions. Hence, MILS-18 summarizes the research at the forefront of medicinal inorganic chemistry, including studies on the next-generation, tailor-made anticancer drugs. All this and more is treated in an authoritative and timely manner in the 17 stimulating chapters of this book, written by 39 internationally recognized experts from 10 nations (from the US via Europe to China and Australia). The impact of this vibrant research area is manifested by more than 2700 references, nearly 150 illustrations (more than half in color) and several comprehensive tables. Metallo-Drugs: Development and Action of Anticancer Agents is an essential resource for scientists working in the wide range from enzymology, material sciences, analytical, organic, and inorganic biochemistry all the way through to medicine including the clinic... not forgetting that it also provides excellent information for teaching.

The field of molecular medicine covers the medical interventions targeting molecular structures and mechanisms that are involved in disease progression. In cancer, several molecular mechanisms have been shown to impact its progression, aggressiveness and chemoresistance. Increasing evidence demonstrates the role of nanotechnology and outcome of molecular therapy.Several books have discussed molecular biology and mechanisms involved in cancer, but this text gives an account of molecular therapeutics in cancer relating to advancements of nanotechnology. It provides a description of the multidisciplinary field of molecular medicines and its targeted delivery to cancer using nanotechnology.Key Features:Provides current information in the multidisciplinary field of molecular medicines and its targeted delivery to cancer using nanotechnologyPresents important aspects of nanotechnology in the site-specific delivery of anticancer agentsIncludes up to date information on oligonucleotide and gene based therapies in cancerDescribes small targeted molecules, antibodies and oligonucleotides which have shown to selectively target the molecular structures thereby influencing signal transductionFacilitates discussion between researchers involved in cancer therapy and nanoscientists

Due to the resultant health consequences and considerable increase in prevalence, obesity has become a major worldwide health problem. “Obesity and Lipotoxicity” is a comprehensive review of the recent researches to provide a better understanding of the lipotoxicity-related mechanisms of obesity and the potential for the development of new treatment strategies. This book overviews the biochemical pathways leading to obesity-related metabolic disorders that occur subsequent to lipotoxicity. Chapters examine the deleterious effects of nutrient excess at molecular level including the cellular and molecular aspects of breast cancer, resistance to leptin, insulin, adiponectin, and interconnection between the circadian clock and metabolic pathways during high-fat feeding. “Lipotoxicity and Obesity” will be a useful resource for clinicians and basic science researchers, such as biochemists, toxicologists, immunologists, nutritionists, adult and pediatric endocrinologists, cardiologists, as well as students who are thought in this field.

Comprehensive Toxicology, Third Edition, Fifteen Volume Set discusses chemical effects on biological systems, with a focus on understanding the mechanisms by which chemicals induce adverse health effects. Organized by organ system, this comprehensive reference work addresses the toxicological effects of chemicals on the immune system, the hematopoietic system, cardiovascular system, respiratory system, hepatic toxicology, renal toxicology, gastrointestinal toxicology, reproductive and endocrine toxicology, neuro and behavioral toxicology, developmental toxicology and carcinogenesis, also including critical sections that cover the general principles of toxicology, cellular and molecular toxicology, biotransformation and toxicology testing and evaluation. Each section is examined in state-of-the-art chapters written by domain experts, providing key information to support the investigations of researchers across the medical, veterinary, food, environment and chemical research industries, and national and international regulatory agencies. Thoroughly revised and expanded to 15 volumes that include the latest advances in research, and uniquely organized by organ system for ease of reference and diagnosis, this new edition is an essential reference for researchers of toxicology. - Organized to cover both the fundamental principles of toxicology and unique aspects of major organ systems - Thoroughly revised to include the latest advances in the toxicological effects of chemicals on the immune system - Features additional coverage throughout and a new volume on toxicology of the hematopoietic system - Presents in-depth, comprehensive coverage from an international author base of domain experts

Emerging Nanotechnologies for Diagnostics, Drug Delivery and Medical Devices covers the modern micro and nanotechnologies used for diagnosis, drug delivery, and theranostics using micro, nano, and implantable systems. In-depth coverage of all aspects of disease treatment is included. In addition, the book covers cutting-edge research and technology that will help readers gain knowledge of novel approaches and their applications to improve drug/agent specificity for diagnosis and efficient disease treatment. It is a comprehensive guide for medical specialists, the pharmaceutical-industry, and academic researchers discussing the impact of nanotechnology on diagnosis, drug delivery, and theranostics. - Gives readers working in immunology, drug delivery, and medicine a greater awareness on how novel nanotechnology orientated methods can help improve treatment - Provides readers with backgrounds in nanotechnology, chemistry, and materials science an understanding on how nanotechnology is used in immunology and drug delivery - Includes focused coverage of the use of nanodevices in diagnostics, therapeutics, and theranostics not offered by other books

Discussing recent findings, up-to-date research, and novel strategies, the book integrates perspectives from pharmacology, toxicology, and biochemistry to illustrate the potential of lysosomes in drug discovery and development.• Explores basic principles and properties of lysosomes that allow them to act as regulators of cell metabolism, therapeutic targets, and sites for activation of drug conjugates • Discusses the role of lysosomes in metabolism, drug targeting, apoptosis, cancer, aging, inflammation, autophagy, metabolism, toxicity, and membrane repair• Introduces new pathways in therapeutic development and new mechanisms in drug development

Endothelium, the new volume in the Advances in Pharmacology series, presents readers with a variety of chapters that cover various endothelium-derived mediators and their changes with gender, and during vascular development, senescence, and hypertensive disorders. Topics include endothelium, nitric oxide, gap junctions, potassium channels, endothelin, vascular development, vascular permeability, gender, aging, and preeclampsia. With contributions from the best authors in the field, the volume is an essential resource for pharmacologists, immunologists, and biochemists alike. - Contains contributions from the best authors in the field - Provides an essential resource for pharmacologists, immunologists, and biochemists - Covers endothelium-derived mediators and their changes

This volume examines our current understanding of the biological effects of fibrous and particulate substances, including discussions on nanoparticles. It offers comprehensive information on the latest insights into the immunological effects of various irritants on the human body. Readers will benefit from the contributing authors'diverse perspectives and extensive discussions of key issues, which include molecular alterations of the immune system and autoimmune diseases in connection with asbestos and silica, among others. The chapters also discuss recommendations, practical methods, and nanosafety science in situations involving exposure to nanotoxic substances. Edited in collaboration with the Japanese Society for Hygiene, this book provides up-to-date information on the immunological effects of nanotoxic substances to researchers interested in environmental and occupational health. Presenting a number of recent concepts and findings in the field, it enables readers to gain a comprehensive knowledge of health problems caused by environmental fibrous and particulate substances.

“Frontiers in Anti-Cancer Drug Discovery” is an Ebook series devoted to publishing the latest and the most important advances in Anti-Cancer drug design and discovery. Eminent scientists write contributions on all areas of rational drug design and drug discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, recent important patents, and structure-activity relationships. The Ebook series should prove to be of interest to all pharmaceutical scientists involved in research in Anti-Cancer drug design and discovery. Each volume is devoted to the major advances in Anti-Cancer drug design and discovery. The Ebook series is essential reading to all scientists involved in drug design and discovery who wish to keep abreast of rapid and important developments in the field. The fifth volume of the series features chapters on the following topics: -Nutraceuticals and natural food products for cancer treatment -Pharmacogenomics in Anti-cancer treatment -Cancer stem cells -Potassium channel targeting for brain tumor treatment -Sorafenib in the management of hepatocellular carcinoma …and more.

Venom research and technology has advanced greatly, rapidly transforming our knowledge of reptile venoms. Research advances, like the development of molecular systematics, provide the framework necessary to reconstruct the evolutionary history of glands and fangs. Such research developments have expanded our understanding of venom's evolution and its usefulness in therapeutic development. The results of this punctuated toxin molecular evolutionary expansion include protein neofunctionalization. While these changes may impact antivenom efficacy, this molecular diversity also facilitates their usefulness in the development of novel drug therapies. Venomous Reptiles And Their Toxins brings together the world's leading toxinologists in this comprehensive study of the entire scope of reptile venoms, from clinical effects to evolution to drug design and development. The book contains detailed applied chapters on clinical care of the envenomed patient, ineffective traditional or modern remedies, occupational considerations involved in the maintenance of institutional venomous reptile collections, veterinary care for venomous reptiles and research methods used in venom research. This book also devotes a chapter to each toxin class found in reptile venoms, detailing the full trajectory of research on the peptide or protein in question. These chapters discuss each toxin's respective role in the envenomation process through to how each has been explored for their biomedical potential. This book is a unique resource for anyone working with venomous reptiles.

Biological toxins are an important part of our world, a reality with which we need to cope, so in parallel with understanding their mechanisms of action and thereby improving our fundamental knowledge, there are successful efforts to utilize them as therapeutics against some debilitating human and animal diseases. In view of the complexity of different types of biotoxins and the broad range of toxin structure, physiology, utility, and countermeasures including regulatory issues, it was thus aimed to compile a book on biotoxins and bioweapons. This reference work in the Toxinology handbook series gathers together knowledge from around the globe about naturally inspired and manufactured biological weapons. The authors describe how they work; how authorities may detect their presence, prevent their use, and diagnose their impacts; and the means by which medical and paramedical professionals may treat victims. Also described are how they have been used to further our knowledge and what insights they have given us into evolutionary and physiological processes. Finally, it is also discussed how these toxins can be used as therapeutics and what the implications of such therapeutics are to their use as biothreat agents. This volume provides a reference accessible to scientists, educators, and medical experts alike with an interest in biotoxins, focusing on the major toxins used as bioweapons. Regulatory agencies will also benefit from the information provided in this book. Some in the intended audience may need to understand how they elicit their effects and how we can defend ourselves against them. Others may be interested in the sometimes colorful histories that surround this subset of biotoxins that can be and, in some cases, have been used as weapons.

Frontiers in Clinical Drug Research - Anti-Cancer Agents should prove to be a valuable resource for pharmaceutical scientists and postgraduate students seeking updated and critical information for developing clinical trials and devising research plans in the field. The chapters featured in each volume are written by leading experts in oncology and clinical pharmacology. The eBook series is essential reading for all scientists involved in clinical drug research who wish to keep abreast of rapid and important developments in the development of anti-cancer agents. The contents of this volume include reviews on dendrimers for anti-cancer drug delivery, treatment methods for advanced cutaneous squamous cell carcinoma, targeting heat shock proteins for cancer treatment, Bayesian systems for optimizing treatment protocols in oncology and much more.

In this second edition of Post-Genomic Cardiology, developing and new technologies such as translational genomics, next generation sequencing (NGS), bioinformatics, and systems biology in molecular cardiology are assessed in light of their therapeutic potential. As new methods of mutation screening emerge, both for the genome and for the'epigenome, comprehensive understanding of the many mutations that underlie cardiovascular diseases and adverse drug reactions is within our reach. This book, written by respected cardiologist José Marín-García, features discussion on the Hap-Map: the largest international effort to date aiming to define the differences between our individual genomes. This unique reference further reviews and investigates genome sequences from our evolutionary relatives that could help us decipher the signals of genes, and offers a comprehensive and critical evaluation of regulatory elements from the complicated network of the background DNA. - Offers updated discussion of cutting-edge molecular techniques including new genomic sequencing / NGS / Hap-Map / bioinformatics / systems biology approaches - Analyzes mitochondria dynamics and their role in cardiac dysfunction, up-to-date analysis of cardio-protection, and cardio-metabolic syndrome - Presents recent translational studies, gene therapy, transplantation of stem cells, and pharmacological treatments in CVDs

This book consists of 4 volumes containing about 70 chapters covering all the major aspects of the growing area of nanomedicine. Leading scientists from 15 countries cover all major areas of nanobiomedical research — materials for nanomedicine, application of nanomedicine in therapy of various diseases, use of nanomedicines for diagnostic purposes, technology of nanomedicines, and new trends in nanobiomedical research.This is the first detailed handbook specifically addressing various aspects of nanobiomedicine. Readers are treated to cutting-edge research and the newest data from leading researchers in this area.

Still the most comprehensive reference source on the development, production and therapeutic application of antibodies, this second edition is thoroughly updated and now has 30% more content. Volume 1 covers selection and engineering strategies for new antibodies, while the second volume presents novel therapeutic concepts and antibodies in clinical study, as well as their potential. Volumes 3 and 4 feature detailed and specific information about each antibody approved for therapeutic purposes, including clinical data. This unique handbook concludes with a compendium of marketed monoclonal antibodies and an extensive index. Beyond providing current knowledge, the authors discuss emerging technologies, future developments, and intellectual property issues, such that this handbook meets the needs of academic researchers, decision makers in industry and healthcare professionals in the clinic.

The highly successful Reviews of Physiology, Biochemistry and Pharmacology continue to offer high-quality, in-depth reviews covering the full range of modern physiology, biochemistry and pharmacology. Leading researchers are specially invited to provide a complete understanding of the key topics in these archetypal multidisciplinary fields. In a form immediately useful to scientists, this periodical aims to filter, highlight and review the latest developments in these rapidly advancing fields.

This atlas contains more than 700 illustrations that the authors have collected over the years as well as references and information pertaining to recently developed drug classes, including biologics. It is a useful bench reference for practicing pathologists and may also be used as a reference text by other experts from related fields. The atlas is organised into different chapters based on systemic pathology. Each chapter has illustrations with legends, and the atlas includes some rare examples of unique lesions found during toxicity studies over many years.

The most trusted all-in-one overview of the biomedical and environmental aspects of toxicology--NOW more complete, up-to-date, and in full color The world's leading and most authoritative textbook on poisons has more to offer students,toxicologists, and pharmacologists than ever before. Now in full color, and thoroughly revised, the eighth edition of Casarett & Doull's TOXICOLOGY: The Basic Science of Poisons not only delivers a comprehensive review of the essential components of toxicology, it offers the most up-to-date, revealing, and in-depth look at the systemic responses of toxic substance available anywhere. Combined with the latest thinking by the field's foremost scholars plus solid coverage of general principles, modes of action, and chemical-specific toxicity, this landmark text continues to set the standard for toxicology references. NEW to the Eighth Edition FULL-COLOR design to allow for a clearer interpretation of the basic components of toxicology featured throughout the text EXPANDED tables, illustrations, and other visuals are updated with state-of-the-art standards that makes this edition even more current and relevant DVD with image bank features all tables and illustrations from the text in presentation-ready format NEW CHAPTERS include'Toxic Effects of Calories'and'Toxic Effects of Nanoparticles'

The World Health Organization has identified chronic alcohol consumption as one of the top ten risk factors for worldwide burden of disease. The International Agency for Research on Cancer has identified alcohol as carcinogenic to humans, including cancers of the upper aerodigestive tract, colon, liver and breast. Alcohol's actions may be direct e.g. effects on retinoic acid and one-carbon metabolism, or indirect, through metabolites such as acetaldehyde and reactive oxygen species or through various signaling pathways that influence cell cycle and apoptosis that may contribute to carcinogenesis. This report reviews the state of the art in alcohol-related cancer research in ten chapters.

This book provides the current state of knowledge of basic mechanisms of adverse drug reactions (ADRs). The main focus is on idiosyncratic drug reactions because they are the most difficult to deal with. It starts with a general description of the major targets for ADRs followed by a description of what are presently believed to be mediators and biochemical pathways involved in idiosyncratic drug reactions. There is also a description of several examples of ADRs that serve to illustrate specific aspects of ADR mechanisms. Eventually the book shows that ultimately better methods are needed to predict which drug candidates are likely to cause ADRs and which patients are at increased risk. But at present research seems to be far from this goal.

'Apoptosome'is the first book that presents a concise synthesis of recent developments in the understanding of how the activation of the cell death cascade is handled by a cytosolic signalling platform known as the apoptosome. The book also discusses how insights into the regulation of apoptosome may be exploited for designing new drugs aimed at interfere with a plethora of pathogenetic processes involved in human diseases. The authors emphasize novel translational approaches that are rapidly moving from the laboratory bench top to the patient's bedside for the future treatment of diseases associated with apoptosis. This book will be a valuable resource for researchers investigating the role of apoptosome-dependent cell death in cancer and other diseases, for researchers investigating the molecular mechanism of chemotherapeutic agents and drug-resistance and for physicians using chemotherapeutic agents. Additionally, this book will be an important educational source for PhD students and MD students specializing in molecular and cell biology, and to anybody interested in science, medicine, as well as in recent developments of the ideas and concepts of the molecular biology of programmed cell death.

With the prevalence of neurodegenerative diseases on the rise as average life expectancy increases, the hunt for effective treatments and preventive measures for these disorders is a pressing challenge. Neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis have been termed ‘protein misfolding disorders'that are char- terized by the neural accumulation of protein aggregates. Manipulation of the cellular stress response involving the induction of heat shock proteins offers a the- peutic strategy to counter conformational changes in neural proteins that trigger pathogenic cascades resulting in neurodegenerative diseases. Heat shock proteins are protein repair agents that provide a line of defense against misfolded, aggregati- prone proteins. Heat Shock Proteins and the Brain: Implications for Neurodegenerative Diseases and Neuroprotection reviews current progress on neural heat shock proteins (HSP) in relation to neurodegenerative diseases (Part I), neuroprotection (Part II), ext- cellular HSP (Part III) and aging and control of life span (Part IV). Key basic and clinical research laboratories from major universities and hospitals around the world contribute chapters that review present research activity and importantly project the field into the future. The book is a must read for researchers, postdoctoral fellows and graduate students in the fields of Neuroscience, Neurodegenerative Diseases, Molecular Medicine, Aging, Physiology, Pharmacology and Pathology.

Molecular chaperones are involved in a wide variety of essential cellular processes in living cells. A subset of molecular chaperones have been initially described as heat shock proteins protecting cells from stress damage by keeping cellular proteins in a folding competent state and preventing them from irreversible aggregation. Later it became obvious that molecular chaperones are also expressed constitutively in the cell and are involved in complex processes such as protein synthesis, intracellular protein transport, post-translational modification and secretion of proteins as well as receptor signalling. Hence, it is not surprising that molecular chaperones are implicated in the pathogenesis of many relevant diseases and could be regarded as potential pharmacological targets. Starting with the analysis of the mode of action of chaperones at the molecular, cellular and organismic level, this book will then describe specific aspects where modulation of chaperone action could be of pharmacological and therapeutic interest.

As our understanding of apoptotic pathway expands, we are coming to realize the great potential of utilizing this pathway to treat diseases such as cancer. The book attempts to review, summarize, and speculate on the apoptotic pathways, how are they regulated and how targeted therapies are being used to treat a wide variety of diseases. Special emphasis is placed on cancer since new treatments either being developed or currently in the clinical setting are showing great promise to increase survival rates for cancer patients. Chapters will address the biology behind regulating the apoptotic pathways and what goes wrong in disease states whereas other chapters will concentrate on new therapies targeting apoptotic pathways. The reader by the end of the book should have greater insight into the understanding and utilization of apoptotic pathways to fight diseases such as cancer.