This updated and expanded volume gives new insights on ferroptosis – an iron-dependent form of non-apoptotic cell death. The collection of chapters discusses the two major pathways through which ferroptosis can occur: the extrinsic or transporter-dependent pathway and the intrinsic or enzyme-regulated pathway. Readers will gain an understanding of the multiple levels, on which this special cell death is regulated. Hence, the contributions will take a closer look at epigenetic, transcriptional, posttranscriptional and posttranslational layers. Among the described regulators and transcription factors are GPX4, ACSL4 and NFE2L2. This edited volume collects reviews related to current knowledge on the integrated molecular machinery of ferroptosis, thereby also describing how dysregulated ferroptosis is involved in human diseases.
This book sheds new light on ferroptosis, as an only recently recognised form of regulated cell death. Its respective chapters address the numerous implications that ferroptosis can have for virtually all aspects of metabolism. They also share insights on the morphological characterisation of ferroptosis and highlight the different pathways of induction. Accordingly, the book offers a unique perspective on a mechanism that is involved in a multitude of pathologies, including cancer cell death, neurotoxicity, neurodegenerative diseases, acute renal failure, drug-induced hepatotoxicity, tissue ischemia/reperfusion injury, and T cell immunity. Readers will learn in which cell types this form of regulated cell death is likely to occur, and how it can be pharmacologically influenced, making the book a fascinating and informative read not only for scientists working in cell biology, but also for clinicians in the field of cancer research.
This volume examines in detail the role of chronic inflammatory processes in the development of several types of cancer. Leading experts describe the latest results of molecular and cellular research on infection, cancer-related inflammation and tumorigenesis. Further, the clinical significance of these findings in preventing cancer progression and approaches to treating the diseases are discussed. Individual chapters cover cancer of the lung, colon, breast, brain, head and neck, pancreas, prostate, bladder, kidney, liver, cervix and skin as well as gastric cancer, sarcoma, lymphoma, leukemia and multiple myeloma.
Recent studies have highlighted that epithelial-mesenchymal transition (EMT) is not only about cell migration and invasion, but it can also govern many other important elements such as immunosuppression, metabolic reprogramming, senescence-associated secretory phenotype (SASP), stem cell properties, therapy resistance, and tumor microenvironment interactions. With the on-going debate about the requirement of EMT for cancer metastasis, an emerging focus on intermediate states of EMT and its reverse process mesenchymal-epithelial transition (MET) offer new ideas for metastatic requirements and the dynamics of EMT/MET during the entire metastatic cascade. Therefore, we would like to initiate discussions on viewing EMT and its downstream signaling networks as a fulcrum of cellular plasticity, and a facilitator of the adaptive responses of cancer cells to distant organ microenvironments and various therapeutic assaults. We hereby invite scientists who have prominently contributed to this field, and whose valuable insights have led to the appreciation of epithelial-mesenchymal plasticity as a more comprehensive mediator of the adaptive response of cancer cells, with huge implications in metastasis, drug resistance, tumor relapse, and patient survival.
Mitochondria are subcellular organelles evolved by the endosymbiosis of bacteria with eukaryotic cells. They are the main source of ATP in the cell and engaged in other aspects of cell metabolism and cell function, including the regulation of ion homeostasis, cell growth, redox status, and cell signaling. Due to their central role in cell life and death, mitochondria are also involved in the pathogenesis and progression of human diseases/conditions, including neurodegenerative and cardiovascular disorders, cancer, diabetes, inflammation, and aging. However, despite the increasing number of studies, precise mechanisms whereby mitochondria are involved in the regulation of basic physiological functions, as well as their role in the cell under pathophysiological conditions, remain unknown. A lack of in-depth knowledge of the regulatory mechanisms of mitochondrial metabolism and function, as well as interplay between the factors that transform the organelle from its role in pro-survival to pro-death, have hindered the development of new mitochondria-targeted pharmacological and conditional approaches for the treatment of human diseases. This book highlights the latest achievements in elucidating the role of mitochondria under physiological conditions, in various cell/animal models of human diseases, and in patients.
This book illustrates the intimate relationship between alveolar macrophages and Mycobacterium tuberculosis (M.tb.), and the former’s role in both innate and adaptive immunity against M.tb. It covers research done over the last decade. It also explores the role of macrophage death following infection with M.tb. in determining whether successful immunity is stimulated, or whether clinical disease develops; furthermore, the function of host lipid mediators in macrophage death modality are addressed. The book also illustrates how the balance between prostaglandins and lipoxins determines whether infected macrophages undergo apoptosis or necrosis, which is the ultimate factor in the outcome of infection. Finally, it is a synthesis of the authors’ recent studies and the studies of others to offer a new understanding of immunity to tuberculosis.
The complex roles of glutathione and sulfur amino acids in human health Glutathione (γ-L-glutamyl-L-cysteinylglycine, GSH) is a major antioxidant acting as a free radical scavenger that protects the cell from reactive oxygen species (ROS). Sulfur amino acids (SAAs), such as methionine and cysteine, play a critical role in the maintenance of health. GSH depletion as well as alterations of SAA metabolism are linked to a host of disease states including liver cirrhosis, various pulmonary diseases, myocardial ischemia and reperfusion injury, aging, Parkinson's disease, Alzheimer's disease, sepsis, and others. This book provides researchers with a comprehensive review of the biochemistry, absorption, metabolism, biological activities, disease prevention, and health promotion of glutathione and sulfur amino acids. The twenty-two chapters explore such topics as: Chemistry, absorption, transport, and metabolism of GSH and sulfur amino acids Antioxidant and detoxification properties of GSH and sulfur amino acids, highlighting the enzymatic systems involved in antioxidant defenses Biological activities of GSH and sulfur amino acids and their role in modulating cell processes Role of GSH and sulfur amino acid deficiency and alteration in the onset of diseases and in aging Protective effects exerted by GSH and sulfur amino acids when used as drugs, functional foods, and nutraceuticals in humans and animals Special attention is paid to the molecular mechanisms for the modulation of transcription factors and enzyme activities, as well as the nutritional and therapeutic significance of dietary sulfur amino acids as shown in human and animal models. With more than 2,000 scientific references, this book provides food scientists, nutritionists, biochemists, food technologists, chemists, molecular biologists, and public health professionals with a comprehensive and up-to-date examination of glutathione and sulfur amino acids in human health and disease.
Proton and Carbon Ion Therapy is an up-to-date guide to using proton and carbon ion therapy in modern cancer treatment. The book covers the physics and radiobiology basics of proton and ion beams, dosimetry methods and radiation measurements, and treatment delivery systems. It gives practical guidance on patient setup, target localization, and treatment planning for clinical proton and carbon ion therapy. The text also offers detailed reports on the treatment of pediatric cancers, lymphomas, and various other cancers. After an overview, the book focuses on the fundamental aspects of proton and carbon ion therapy equipment, including accelerators, gantries, and delivery systems. It then discusses dosimetry, biology, imaging, and treatment planning basics and provides clinical guidelines on the use of proton and carbon ion therapy for the treatment of specific cancers. Suitable for anyone involved with medical physics and radiation therapy, this book offers a balanced and critical assessment of state-of-the-art technologies, major challenges, and the future outlook of proton and carbon ion therapy. It presents a thorough introduction for those new to the field while providing a helpful, up-to-date reference for readers already using the therapy in clinical settings.
The imbalance between the production of reactive oxygen species (ROS) and antioxidant defenses determines a state known as oxidative stress. Higher levels of pro-oxidants compared to antioxidant defenses may generate oxidative damage, which, in turn, may lead to modifications in cellular proteins, lipids, and DNA, reducing functional capacity and increasing the risk of diseases. Nevertheless, the clearance of harmful reactive chemical species is achieved by the antioxidant defense systems. These protection systems are referred to as the first and second lines of defense and comprise the classic antioxidants, enzymatic and nonenzymatic defenses, including glutathione. This book presents and discusses the advancement of research on health and diseases and their underlying mechanisms, exploring mainly aspects related to the glutathione antioxidant system.
Glutathione (GSH) has been described for a long time just as a defensive reagent against the action of toxic xenobiotics (drugs, pollutants, carcinogens), both directly and as a cofactor for GSH transferases. As a prototype antioxidant, it has been involved in cell protection from the noxious effect of excess oxidant stress, both directly and as a cofactor of glutathione peroxidases. In addition, it has long been known that GSH is capable of forming disulfide bonds with cysteine residues of proteins, and the relevance of this mechanism ("S-glutathionylation") in regulation of protein function has been well documented in a number of research fields. Rather paradoxically, it has also been highlighted that GSH—and notably its catabolites, as originated by metabolism by gamma-glutamyltransferase—can promote oxidative processes, by participating in metal ion-mediated reactions eventually leading to formation of reactive oxygen species and free radicals. Also, a fundamental role of GSH has been recognized in the storage and transport of nitric oxide (NO), in the form of S-nitrosoglutathione (GSNO). The significance of GSH as a major factor in regulation of cell life, proliferation, and death, can be regarded as the integrated result of all these roles, as well as of more which are emerging in diverse fields of biology and pathophysiology. Against this background, modulation of GSH levels and GSH-related enzyme activities represents a fertile field for experimental pharmacology in numerous and diverse perspectives of animal, plant and microbiologic research. This research topic includes 14 articles, i.e. 4 Opinion Articles, 6 Reviews, and 4 Original Research Articles. The contributions by several distinguished research groups, each from his own standpoint of competence and expertise, provide a comprehensive and updated view over the diverse roles, the changing faces of GSH and GSH-related enzymes in cell’s health, disease and death.
