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This volume presents state-of-the-art information on each of the arms of the unfolded protein response (UPR), how their activation/repression are regulated, integrated, and coordinated, how UPR components affect cancer cell biology and responsiveness to therapeutic interventions, and how UPR components/activities offer potentially novel targets for drug discovery, repurposing, and development. The volume will provide the most recent information on the signaling and regulation of the UPR, explore examples of how the UPR and/or specific components contribute to cancer biology, and identify and explore specific examples of potently new actionable targets for drug discovery and development from within the UPR and its regulation. Unique to the volume will be a specific focus on the UPR and its role in cancer biology, as well as a discussion of the role of the UPR in drug responses and resistance in cancer.
This volume is divided in six section covering the most experimental approaches involved in the study of the unfolded protein response (UPR) pathway. Chapters detail determination of unfolded protein levels, methods to study UPR signal transmission, analysing the outcomes of the UPR pathway activation, UPR studies in mammalian models, UPR in alternative models, and UPR and disease. 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, The Unfolded Protein Response: Methods and Protocols aims to describe key methods and approaches used in the study of the UPR pathway and its complex cellular implications. Chapter 6 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Protein homeostasis, or “Proteostasis”, lies at the heart of human health and disease. From the folding of single polypeptide chains into functional proteins, to the regulation of intracellular signaling pathways, to the secreted signals that coordinate cells in tissues and throughout the body, the proteostasis network operates to support cell health and physiological fitness. However, cancer cells also hijack the proteostasis network and many of these same processes to sustain the growth and spread of tumors. The chapters in this book are written by world experts in the many facets of the proteostasis network. They describe cutting-edge insights into the structure and function of the major chaperone and degradation systems in healthy cells and how these systems are co-opted in cancer cells and the cells of the tumor microenvironment. The chapters also cover therapeutic interventions such as the FDA-approved proteasome inhibitors Velcade and Krypolis as well as other therapies currently under clinical investigation to disarm the ability of the proteostasis network to support malignancy. This compendium is the first of its kind and aims to serve as a reference manual for active investigators and a primer for newcomers to the field. This book is dedicated to the memory of Susan Lindquist, a pioneer of the proteostasis field and a champion of the power of basic scientific inquiry to unlock the mechanisms of human disease. The chapter “Reflections and Outlook on Targeting HSP90, HSP70 and HSF1 in Cancer: A Personal Perspective” is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging is an eleven volume series that discusses in detail all aspects of autophagy machinery in the context of health, cancer, and other pathologies. Autophagy maintains homeostasis during starvation or stress conditions by balancing the synthesis of cellular components and their deregulation by autophagy. This series discusses the characterization of autophagosome-enriched vaccines and its efficacy in cancer immunotherapy. Autophagy serves to maintain healthy cells, tissues, and organs, but also promotes cancer survival and growth of established tumors. Impaired or deregulated autophagy can also contribute to disease pathogenesis. Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and forward-thinking, these books offer a valuable guide to cellular processes while also inciting researchers to explore their potentially important connections. - Presents the most advanced information regarding the role of the autophagic system in life and death - Examines whether autophagy acts fundamentally as a cell survivor or cell death pathway or both - Introduces new, more effective therapeutic strategies in the development of targeted drugs and programmed cell death, providing information that will aid in preventing detrimental inflammation - Features recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities, including atherosclerosis and CNS tumors, and their development and treatment - Includes chapters authored by leaders in the field around the globe—the broadest, most expert coverage available
Throughout history, arsenic has been used as an effective and lethal poison. Today, arsenic continues to present a real threat to human health all over the world, as it contaminates groundwater and food supplies. Handbook of Arsenic Toxicology presents the latest findings on arsenic, its chemistry, its sources and its acute and chronic effects on the environment and human health. The book takes readings systematically through the target organs, before detailing current preventative and counter measures. This reference enables readers to effectively assess the risks related to arsenic, and provide a comprehensive look at arsenic exposure, toxicity and toxicity prevention. - Brings together current findings on the effects of arsenic on the environment and human health - Includes state-of-the-art techniques in arsenic toxicokinetics, speciation and molecular mechanisms - Provides all the information needed for effective risk assessment, prevention and countermeasure
An overview of the current systems biology-based knowledge and the experimental approaches for deciphering the biological basis of cancer.
Heat shock proteins are emerging as important molecules in the development of cancer and as key targets in cancer therapy. These proteins enhance the growth of cancer cells and protect tumors from treatments such as drugs or surgery. However, new drugs have recently been developed particularly those targeting heat shock protein 90. As heat shock protein 90 functions to stabilize many of the oncogenes and growth promoting proteins in cancer cells, such drugs have broad specificity in many types of cancer cell and offer the possibility of evading the development of resistance through point mutation or use of compensatory pathways. Heat shock proteins have a further property that makes them tempting targets in cancer immunotherapy. These proteins have the ability to induce an inflammatory response when released in tumors and to carry tumor antigens to antigen presenting cells. They have thus become important components of anticancer vaccines. Overall, heat shock proteins are important new targets in molecular cancer therapy and can be approached in a number of contrasting approaches to therapy.
Biological processes are driven by complex systems of functionally interacting signaling molecules. Thus, understanding signaling molecules is essential to explain normal or pathological biological phenomena. A large body of clinical and experimental data has been accumulated over these years, albeit in fragmented state. Hence, systems biological approaches concomitant with the understanding of each molecule are ideal to delineate signaling networks/pathways involved in the biologically important processes. The control of these signaling pathways will enrich our healthier life. Currently, there are more than 30,000 genes in human genome. However, not all the proteins encoded by these genes work equally in order to maintain homeostasis. Understanding the important signaling molecules as completely as possible will significantly improve our research-based teaching and scientific capabilities. This encyclopedia presents 350 biologically important signaling molecules and the content is built on the core concepts of their functions along with early findings written by some of the world’s foremost experts. The molecules are described by recognized leaders in each molecule. The interactions of these single molecules in signal transduction networks will also be explored. This encyclopedia marks a new era in overview of current cellular signaling molecules for the specialist and the interested non-specialist alike During past years, there were multiple databases to gather this information briefly and very partially. Amidst the excitement of these findings, one of the great scientific tasks of the coming century is to bring all the useful information into a place. Such an approach is arduous but at the end will infuse the lacunas and considerably be a streamline in the understanding of vibrant signaling networks. Based on this easy-approach, we can build up more complicated biological systems.
This textbook presents concise chapters written by internationally respected experts on various important aspects of cancer-associated metabolism, offering a comprehensive overview of the central features of this exciting research field. The discovery that tumor cells display characteristic alterations of metabolic pathways has significantly changed our understanding of cancer: while the first description of tumor-specific changes in cellular energetics was published more than 90 years ago, the causal significance of this observation for the pathogenesis of cancer was only discovered in the post-genome era. The first 10 years of the twenty-first century were characterized by rapid advances in our grasp of the functional role of cancer-specific metabolism as well as the underlying molecular pathways. Various unanticipated interrelations between metabolic alterations and cancer-driving pathways were identified and currently await translation into diagnostic and therapeutic applications. Yet the speed, quantity, and complexity of these new discoveries make it difficult for researchers to keep up to date with the latest developments, an issue this book helps to remedy.
Advances in Cancer Research, Volume 150, the latest release in this ongoing series, covers the relationship(s) between autophagy and senescence, how they are defined, and the influence of these cellular responses on tumor dormancy and disease recurrence. Specific sections in this new release include Autophagy and senescence, converging roles in pathophysiology, Cellular senescence and tumor promotion: role of the unfolded protein response, autophagy and senescence in cancer stem cells, Targeting the stress support network regulated by autophagy and senescence for cancer treatment, Autophagy and PTEN in DNA damage-induced senescence, mTOR as a senescence manipulation target: A forked road, and more. - Addresses the relationship between autophagy and senescence in cancer therapy - Covers autophagy and senescence in tumor dormancy - Explores autophagy and senescence in disease recurrence