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Targeted Delivery of Small and Macromolecular Drugs
by Ajit S. Narang Ram I. MahatoSite-specific drug delivery and targeting attracts much research interest from both academia and industry, but because of the many challenges faced in the development of these systems, only a handful of targeted therapies have successfully made it into clinical practice. Focusing on the delivery technologies that utilize both systemic and local rou
Targeted Drug Delivery: Concepts and Design
by Padma V. Devarajan Sanyog JainThis authoritative volume explores the fundamental concepts and numerous applications of targeted delivery of drugs to the body. This compilation has been divided into eight sections comprised of the basic principles of drug targeting, disease and organ/organelle-based targeting, passive and active targeting strategies, and various advanced drug delivery tools such as functionalized lipidic, polymeric and inorganic nanocarriers. Together, the twenty-three chapters cover a wide range of topics in the field, including tumor and hepatic targeting, polymer-drug conjugates, nanoemulsion, physical and biophysical characteristics of nanoparticles, and in vivo imaging techniques, among others. The book also examines advanced characterization techniques, regulatory hurdles and toxicity-related issues that are key features for successful commercialization of targeted drug delivery system products. Targeted Drug Delivery is a comprehensive reference guide for drug delivery researchers, both beginners and those already working in the field.
Targeted Drug Delivery: Methods And Protocols (Methods in Molecular Biology #1831)
by Rachael W. Sirianni Bahareh BehkamThis volume looks at the latest techniques used to enable therapeutic molecules to be targeted for site-specific delivery. The chapters in this book discuss topics such as approaches to express biologically derived and synthetic nanocarriers; strategies to assist in nanocarrier targeting to specific cells and tissues; and methods for evaluating delivery and efficiency for new classes of agents. Written in the highly 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 laboratory protocols, and tips on troubleshooting and avoiding known pitfalls.Cutting-edge and comprehensive, Targeted Drug Delivery: Methods and Protocols is a valuable resource for anyone interested in understanding the diversity of methods used in this evolving field.
Targeted Drug Strategies for Cancer and Inflammation
by Christopher P. Leamon Ann L. JackmanFolate pathways are essential in metabolism and macromolecule synthesis. Antifolate drugs that are largely transported via a high capacity folate transporter (i.e. the reduced-folate carrier) and inhibit folate-dependent enzymes include the dihydrofolate reductase inhibitor, methotrexate, and the thymidylate synthase inhibitors, raltitrexed and pemetrexed. Major advances in folate research made within the last decade include (i) the approval of pemetrexed for the treatment of lung cancer and mesothelioma, and (ii) the demonstration that cell membrane-anchored folate receptors (FR) are exploitable for cancer and inflammatory disease management. FRs are not widely distributed in normal tissues, except on some luminal surfaces; however, they are accessible to systemically administered agents when expressed on many cancers as well as on activated macrophages involved in various inflammatory diseases. High affinity folate-radioisotope conjugates have been developed for imaging pathogenic FR-positive diseases, including cancer. Since the FR transports folates via a low capacity but high affinity endocytic pathway, a variety of FR-targeted antifolate drugs and folate conjugates bearing a wide range of payloads (including cytotoxic drugs) are currently being developed which exploit this property. The FR is also being utilized in immunotherapy approaches for the treatment of overexpressing cancers.
Targeted Intracellular Drug Delivery by Receptor Mediated Endocytosis (AAPS Advances in the Pharmaceutical Sciences Series #39)
by Padma V. Devarajan Prajakta Dandekar Anisha A. D’SouzaThis book elaborates on drug delivery targeting via intracellular delivery, specifically through the Receptor Mediated Endocytosis (RME) approach, due to the involvement of cellular receptors in various grave diseases. Targeted delivery relies on two basic approaches, passive and active targeting. While passive targeting approaches have shown great promise, the improved selectivity achieved with active targeting approaches has resulted in significantly higher efficacy. Interestingly there are numerous strategies for active targeting, many of which are already highlighted in , Targeted Drug Delivery: Concepts and Applications. Nevertheless an exciting and practical strategy for active targeting, which could enable high intracellular delivery, is through exploitation of RME. Cells in the body express receptors to enable various physiological and biochemical processes. As a result, many of these receptors are overexpressed in pathological conditions, or newer receptors expressed due to defective cellular functioning. RME is based on exploitation of such receptors to achieve intracellular delivery. While targeted delivery can have manifold applications, in this book we focus on two major and challenging therapeutic areas; i) Cancer and ii) Infectious Diseases. Targeted Intracellular Drug Delivery by Receptor Medicated Endocytosis discusses the major receptors that are useful for targeted delivery for these afflictions. A major section of this book is dedicated to details regarding their occurrence and location, the recognition domain of the receptor, structure activity relationship of substrate /ligand for selective binding, ligands explored, antagonists for ligand binding and relevance of these aspects for therapy of cancer and infectious diseases. These facets are elucidated with the help of specific examples from academic research and also emphasize commercial products, wherever relevant. In vitro cellular models relied on for assessing receptor mediated cellular targeting and in vivo models depicting clinical efficacy are focused on in a separate section. Finally, we briefly discuss the regulatory and toxicity issues that may be associated specifically with the RME approach of intracellular drug delivery.
Targeted Intraoperative Radiotherapy in Oncology
by Mohammed Keshtgar Katharine Pigott Frederik WenzTargeted intraoperative radiotherapy is a major advance in the management of cancer patients and has been attracting massive interest worldwide following publication of the results of an important randomized controlled trial in The Lancet. This textbook is designed to introduce this innovative technology in a comprehensive manner to clinicians dealing with cancer patients. Throughout, the emphasis is on practical aspects and the text is supported by many excellent illustrations. The editors of the book have extensive experience in targeted intraoperative radiotherapy and include co-directors of the TARGIT Academy, which runs international training courses on the technology in the United Kingdom and Germany. They have brought together multidisciplinary contributors from different centers across the world who have wide experience in the field and whose work has been recognized internationally. It is the editors' hope that this book will succeed in ensuring that targeted intraoperative radiotherapy is used effectively worldwide.
Targeted Learning in Data Science: Causal Inference For Complex Longitudinal Studies (Springer Series in Statistics)
by Mark J. van der Laan Sherri RoseThis textbook for graduate students in statistics, data science, and public health deals with the practical challenges that come with big, complex, and dynamic data. It presents a scientific roadmap to translate real-world data science applications into formal statistical estimation problems by using the general template of targeted maximum likelihood estimators. These targeted machine learning algorithms estimate quantities of interest while still providing valid inference. Targeted learning methods within data science area critical component for solving scientific problems in the modern age. The techniques can answer complex questions including optimal rules for assigning treatment based on longitudinal data with time-dependent confounding, as well as other estimands in dependent data structures, such as networks. Included in Targeted Learning in Data Science are demonstrations with soft ware packages and real data sets that present a case that targeted learning is crucial for the next generation of statisticians and data scientists. Th is book is a sequel to the first textbook on machine learning for causal inference, Targeted Learning, published in 2011.Mark van der Laan, PhD, is Jiann-Ping Hsu/Karl E. Peace Professor of Biostatistics and Statistics at UC Berkeley. His research interests include statistical methods in genomics, survival analysis, censored data, machine learning, semiparametric models, causal inference, and targeted learning. Dr. van der Laan received the 2004 Mortimer Spiegelman Award, the 2005 Van Dantzig Award, the 2005 COPSS Snedecor Award, the 2005 COPSS Presidential Award, and has graduated over 40 PhD students in biostatistics and statistics.Sherri Rose, PhD, is Associate Professor of Health Care Policy (Biostatistics) at Harvard Medical School. Her work is centered on developing and integrating innovative statistical approaches to advance human health. Dr. Rose’s methodological research focuses on nonparametric machine learning for causal inference and prediction. She co-leads the Health Policy Data Science Lab and currently serves as an associate editor for the Journal of the American Statistical Association and Biostatistics.
Targeted Metallo-Drugs: Design, Development, and Modes of Action (Metal Ions in Life Sciences Series)
by Etelka Farkas Celine J. Marmion Astrid Sigel Helmut Sigel Eva Freisinger Roland K. O. SigelVolume 24, entitled Targeted Metallo-Drugs: Design, Development, and Modes of Action, of the series Metal Ions in Life Sciences (MILS), fosters inter-disciplinary research in the vibrant field of Biological Inorganic Chemistry. Inspired by the clinical success of cisplatin as a leading anticancer drug but mindful of the shortcomings associated with its use including dose-limiting toxic side effects and acquired or intrinsic drug resistance, scientists across the globe have been endeavoring to identify new metallo-drugs for therapeutic exploitation. This has led to innovative metallo-drug candidates that (i) enhance cancer cell selectivity, thus reducing toxic side effects, and/or (ii) possess new modes of action to improve efficacy and also target resistance pathways. This and more are captured in MILS- 24 which consists of 12 comprehensive, well-illustrated, and up to date chapters with over 1600 citations, 100 figures, and 10 tables with key contributions from 32 international experts from Europe, Asia, and North and South America. MILS- 24 not only keeps the scientific community abreast of latest developments, it also serves as an invaluable resource to stimulate further research on targeted metallo-drug design and development. • It covers anticancer, antimicrobial, antiviral, and other agents, such as those targeting tropical diseases and cyanide poisoning and radiometals in molecular imaging and therapy. • It highlights recent metallo-drug developments targeting COVID-19. • It features advanced spectroscopic methods and metallomics as important tools to elucidate the modes of actions of metallo-drugs.
Targeted Molecular Imaging (Imaging in Medical Diagnosis and Therapy)
by Michael J. Welch William C. EckelmanTargeted Molecular Imaging covers the development of novel diagnostic approaches that use an imaging probe and agent to noninvasively visualize cellular processes in normal and disease states. It discusses the concept, development, preclinical studies, and, in many cases, translation to the clinic of targeted imaging agents. The many case studies t
Targeted Muscle Reinnervation: A Neural Interface for Artificial Limbs (Series in Medical Physics and Biomedical Engineering)
by Todd A. Kuiken Aimee E. Schultz Feuser Ann K. BarlowImplement TMR with Your Patients and Improve Their Quality of LifeDeveloped by Dr. Todd A. Kuiken and Dr. Gregory A. Dumanian, targeted muscle reinnervation (TMR) is a new approach to accessing motor control signals from peripheral nerves after amputation and providing sensory feedback to prosthesis users. This practical approach has many advantage
Targeted Protein Degradation: Methods and Protocols (Methods in Molecular Biology #2365)
by Angela M. Cacace Christopher M. Hickey Miklós BékésThis volume contains a collection of innovative techniques for studying targeted protein degradation. Chapters guide readers through heterobifunctional proteolysis-targeting chimeras (PROTACs) approaches, E3 ligase, E3 ligase-induced ubiquitylation, proteomic approaches, novel degrader molecules, molecular glue, and stabilize binding interaction between a target and E3 ubiquitin ligase. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, Targeted Protein Degradation: Methods and Protocols aims to ensure successful results in this emerging field of drug discovery.
Targeted Therapeutics in Melanoma
by F. Stephen Hodi Thomas F. GajewskiMelanoma is an increasingly important public health problem. Although the cause of most malignant melanomas - over-exposure to ultraviolet light - is well known, effective treatment has remained challenging. The past several years have been marked by extraordinary developments in melanoma treatment in the arena of targeted therapeutics. This book describes these ground-breaking discoveries and their implications for clinical use. As melanoma biology is increasingly understood, so the development of targeted therapies for this disease is spurred ahead. This book covers both established signal transduction inhibitors and the fascinating emerging realm of molecularly-guided immunotherapies. This benchmark book provides the most up-to-date information on the new breed of melanoma therapies. Composed of the works of major researchers and clinicians, this book offers new insights, novel approaches, and promising data for effective treatment planning. Illuminating the latest advances in the field, it is a solid resource for clinical oncologists, translational scientists, and basic cancer researchers.
Targeted Therapies
by Daniel GioeliThis volume explores the mechanisms of resistance to targeted therapeutics. The focus is on the cancer cell signaling network, although other mechanisms of resistance including target mutation, and new areas of study such as cancer stem cells are included. Targeted Therapies: Mechanisms of Resistance highlights examples of changes in the signaling network in response to inhibition of a signaling event and underscores the importance in having a mechanistic understanding of the signaling network in cancer for developing effective targeted cancer therapies. Moreover, cutting edge tools to analyze the cell signaling network will be discussed. This includes the leading edge of techniques as well as computational biology and systems theory. This volume provides the reader with both an overview as well as a detailed perspective on the mechanisms of resistance to targeted therapeutics and will be of great value to the oncologist, the physician-scientist treating patients and the translational scientist working on any aspect of targeted therapeutics.
Targeted Therapies for Lung Cancer (Current Cancer Research)
by Ravi SalgiaThis book contextualizes translational research and provides an up to date progress report on therapies that are currently being targeted in lung cancer. It is now well established that there is tremendous heterogeneity among cancer cells both at the inter- and intra-tumoral level. Further, a growing body of work highlights the importance of targeted therapies and personalized medicine in treating cancer patients. In contrast to conventional therapies that are typically administered to the average patient regardless of the patient’s genotype, targeted therapies are tailored to patients with specific traits. Nonetheless, such genetic changes can be disease-specific and/or target specific; thus, the book addresses these issues manifested in the somatically acquired genetic changes of the targeted gene. Each chapter is written by a leading medical oncologist who specializes in thoracic oncology and is devoted to a particular target in a specific indication. Contributors provide an in-depth review of the literature covering the mechanisms underlying signaling, potential cross talk between the target and downstream signaling, and potential emergence of drug resistance.
Targeted Therapies for Solid Tumors
by Antonio Russo Rafael Rosell Christian RolfoThis volume provides readers a comprehensive and state-of-the-art overview about the range of applications of targeted therapies for solid tumors. The sections of the book have been structured to review the oncogene addicted tumors, the pharmacology and clinical development of new molecularly targeted agents, the use of biomarkers as prognostic, predictive and surrogate endpoints, and the evaluation of tumor response and specific malignancies treated with targeted agents. The book also covers some of the newest developments in cancer therapy that are not adequately covered by any current available literature. Written by recognized experts in the field, Targeted Therapies for Solid Tumors: A Handbook for Moving Toward New Frontiers in Cancer Treatment provides a unique and valuable resource in the field of molecular oncology, both for those currently in training, and for those already in clinical or research practice.
Targeted Therapies in Lung Cancer: Management Strategies for Nurses and Practitioners
by Marianne Davies Beth Eaby-SandyThis book aims to educate nurses and advanced practice providers (APP’s) about known mutations, availability of targeted therapy and the management of patients with non-small cell lung cancer (NSCLC). It will educate nurses and practitioners about the scope of therapy to assure safe and effective lung cancer treatment. In this era of personalized medicine, nurses and APP’s are responsible for guiding patients from diagnosis through treatment. This starts with the identification of patients that can benefit from these therapies, the key role of biopsy acquisition (ie. what to test, when and how often) and treatment selection based on the mutation identified. Readers will learn about the mechanisms of action, administration, potential adverse side effects and unique management strategies for these targeted agents. Lung cancer continues to be the leading cause of cancer death in the United States and worldwide. Recent advances in the identification of specific oncogenic mutations that drive cancer development, growth and metastasis have led to major paradigm shifts in lung cancer treatment. Sophisticated methods are required to identify specific mutations at the time of diagnosis. This book explains how molecularly targeted therapies have been developed that target these drivers. To date, several tyrosine kinase inhibitors have been approved to target the epidermal growth factor receptor (EGFR), EML4-ALK ,ROS1 and BRAF. Most recently, immune checkpoint inhibitors have been approved with some indication that efficacy may be enhanced for patients who overexpress PD-L1. While some driver mutations have been identified, there is ongoing investigation into additional mutations. In the case of driver mutations, lung cancers will develop resistance to therapy. This book provides nurses and APP’s with the mechanisms of resistance that have been identified such as T790 mutation and many others in the EGFR mutation, and shows how the next level of drug development is focused on identifying mechanisms of resistance and development of new agents that overcome these mutations. With this book in hand, nurses and practitioners will be able to navigate patients through this ever expanding field of lung cancer treatment.
Targeted Therapies in Oncology
by Giuseppe Giaccone Jean-Charles SoriaSince the last edition of this book, major advances have been made in our understanding of key pathways that control tumor progression. This has led to the development of new anticancer agents that have the ability to block the activity of proteins involved in neoplastic cell development and proliferation. Targeted Therapies in Oncology, Second Edi
Targeted Therapy in Translational Cancer Research
by Apostolia-Maria Tsimberidou Kenneth C. Anderson Ernest Hawk Robert C. Bast Maurie Markman Razelle KurzrockTargeted Therapy in Translational Cancer Research for the Translational Oncology series provides a comprehensive overview of recent developments in our understanding of tumor biology, elucidates the roles of targets and pathways involved in carcinogenesis, and describes current state-of-the-art anticancer therapy, as well as the most promising areas of translational research and targeted therapy. Introduces cutting-edge 'bench to bedside and back' breakthroughs which have transformed the diagnosis, prognosis, and treatment of cancer Covers basic principles of targeted therapy, including immunotherapy and the roles of cancer stem cells, the microenvironment, angiogenesis, epigenetics, microRNAs, and functional imaging in precision medicine Summarises major advances in therapeutic management of hematologic malignancies and solid tumors using conventional therapy, targeted therapy, immunotherapy, or novel treatment modalities
Targeted Therapy of Acute Myeloid Leukemia
by Michael AndreeffThis book provides an unprecedented overview of "Targeted Therapies" for acute myeloid leukemias. It aims at an almost comprehensive coverage of the diverse therapeutic strategies that have been developed during the last decade and are now being evaluated in early clinical trials. Paired and authoritative chapters by leading research scientists and clinicians explain basic concepts and clinical translation of topics that include the underlying genetic and proteomic abnormalities of AML, the development of novel nucleoside analogues, the roles of microRNAs, apoptosis regulators Bcl-2 and p53 and of critical cell signaling proteins such as PIM, FLT3, Raf/MEK, PI3K/AKT/mTOR and aurora kinases. Chapters on epigenetic mechanisms, nuclear receptors, cell surface antigens, the hypoxic leukemia microenvironment, stem cells and leukemia metabolism provide insights into leukemia cell vulnerabilities. Cell therapies utilizing T-, NK- and mesenchymal stem cells and progress in hematopoietic transplantation strategies round up this overview of the multi-dimensional therapeutic landscape in which leukemia specialists develop treatment strategies that are expected to make "leukemia history" in the near future.
Targeted Therapy of Colorectal Cancer Subtypes (Advances in Experimental Medicine and Biology #1110)
by Peter JordanColorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Recent years have increased significantly our understanding of the genetic alterations that can underlie CRC, but also unraveled the molecular heterogeneity of the disease. Although a simple correlation between genetic pathways, histopathological features and clinical outcome cannot be established, the heterogeneity of CRC is also an opportunity for the development of targeted therapeutic approaches, able to treat an individual tumor with higher efficiency and less toxic side effects. One CRC subtype is characterized by high mutation rates (MSI-H), DNA methylation changes (CIMP-H), mutation in the BRAF oncogene and occurrence of serrated adenomas in the proximal colon. Other groups prevail in the distal colon and consist of either adenomatous polyps with chromosomal aberrations (CIN) and WNT pathway activation, or carry frequent KRAS mutation and metabolic deregulation, or have strong mesenchymal and infiltrative characteristics. Characterization of driver-mutation events in these CRC subgroups has led to the development of specific drugs targeting, for example, the MAPK pathway, but initial clinical trials have revealed unexpected response rates. The collection of chapters in this volume address the biology of specific CRC subtypes and how these may be targeted to improve precision therapy and clinical benefit for the patients.
Targeting Autophagy in Cancer Therapy
by Jin-Ming YangThis volume will detail the current state and perspectives of autophagy-based cancer therapy. Covering a wide range of topics, it will include an overview of autophagy as a therapeutic target in cancer, autophagy modulators as cancer therapeutic agents, implications of micro-RNA-regulated autophagy in cancer therapy, modulation of autophagy through targeting PI3 kinase in cancer therapy, targeting autophagy in cancer stem cells, and roles of autophagy in cancer immunotherapy. In addition, the volume will review applications of system biology and bioinformatics approaches to discovering cancer therapeutic targets in the autophagy regulatory network. The volume will be beneficial for a variety of basic and clinical scientists, including cancer biologists, autophagy researchers, pharmacologists, and clinical oncologists who wish to delve more deeply into this field of cancer research. This volume will be the first book to focus solely on autophagy as a target in cancer therapy. As well, it will comprehensively discuss the roles of autophagy in most currently available cancer treatments.
Targeting Biofilms in Translational Research, Device Development, and Industrial Sectors
by Dustin L. WilliamsThis book offers a much-needed discussion on the targeting of biofilm-related infections. Chapters include discussions on the impact of biofilm on medical implants, industrial applications, as well as wound and tissue infections. It also offers discussions on regulatory management for industrial sectors and medical environments. Given that there continues to be a paucity of effective antimicrobial products, devices, and coatings in clinical and industrial use that effectively reduce rates of infection or biofilm-related problems, Targeting Biofilms in Translational Research, Device Development, and Industrial Sectors, offers a fresh and much-needed perspective aimed at helping create healthier controlled environments and safer devices. This comprehensive book is indispensable for industrial and academic translational researchers, device developers, and regulatory experts looking to create more effective antimicrobial products.
Targeting Cellular Signalling Pathways in Lung Diseases
by Kamal Dua Raimar Löbenberg Ângela Cristina Malheiros Luzo Shakti Shukla Saurabh SatijaThe book comprehensively reviews and provides detailed insight into the cellular and molecular signalling mechanisms involved in pathophysiology of various respiratory diseases, towards developing effective therapeutic strategies in the management and treatment of lung disease. It also covers promising advances in the field of therapeutics that could lead to novel clinical therapies capable of preventing or reversing the disease features including novel strategies for targeting chronic lung diseases using advanced drug delivery systems. Importantly, the book examines the significance and relevance of the plant extracts and their constituents with therapeutic efficiencies against lung diseases. As such, the book offers a blend of translational, biological, chemical, and drug delivery aspects relevant to respiratory diseases, thus, offering a valuable resource for pulmonologists and translational researchers working in the field of pulmonary biology and respiratory medicine.
Targeting Chitin-containing Organisms (Advances in Experimental Medicine and Biology #1142)
by Qing Yang Tamo FukamizoThis book provides a comprehensive overview of chitin biology and chitin metabolism related enzymes. Chitin, the second most abundant biopolymer in nature after to cellulose, is a linear biopolymer composed of β-1,4-linked N-acetylglucosamine (GlcNAc), and an essential component in the exoskeletons of insects, mites, ticks and crustaceans, the egg shells of parasitic nematodes, and fungal cell walls. Although some chitin-containing organisms are a threat to human health, food safety and agricultural production, non-chitin containing organisms like humans, mammals and plants have an innate immune response to these hazardous organisms. The book provides researchers and students with information on the recent research advances concerning the biology of chitin-containing organisms as well as cross-talks between chitin-containing and non-chitin-containing organisms. Highlighting chitin remodeling enzymes and inhibitors, it also offers drug developers essential insights into designing specific molecules for the control of hazardous chitin-containing organisms.
Targeting Enzymes for Pharmaceutical Development: Methods and Protocols (Methods in Molecular Biology #2089)
by Nikolaos E. LabrouThis volume explores detailed methods and experimental protocols evaluating the effect of a compound or a mixture of compounds on the action of enzymes that are significant targets in pharmaceuticals. Consisting of three sections, the book delves into recent biocomputing and bioinformatics protocols, state-of-the art modern biophysical, electrophoretic, and chromatographic methods and high-throughput screening approaches, as well as detailed protocols and examples of the inhibition analysis and evaluation of selected enzymes. Written for the highly successful Methods in Molecular Biology series, 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 cutting-edge, Targeting Enzymes for Pharmaceutical Development: Methods and Protocols serves as a vital reference for academics and industry professionals working on expanding our understanding of the wide range of important enzyme targets.