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The PI3Ks control many key functions in immune cells. PI3Ks phosphorylate PtdIns(4,5)P2 to yield PtdIns(3,4,5)P3. Initially, PI3K inhibitors such as Wortmannin, LY294002 and Rapamycin were used to establish a central role for Pi3K pathway in immune cells. Considerable progress in understanding the role of this pathway in cells of the immune system has been made in recent years, starting with analysis of various PI3K and Pten knockout mice and subsequently mTOR and Foxo knockout mice. Together, these experiments have revealed how PI3Ks control B cell and T cell development, T helper cell differentiation, regulatory T cell development and function, B cell and T cell trafficking, immunoglobulin class switching and much, much more. The PI3Kd inhibitor idelalisib has recently been approved for the treatment of B cell lymphoma. Clinical trials of other PI3K inhibitors in autoimmune and inflammatory diseases are also in progress. This is an opportune time to consider a Research Topic considering when what we have learned about the PI3K signalling module in lymphocyte biology and how this is making an impact on clinical immunology and haematology.
This comprehensive encyclopedic reference provides rapid access to focused information on topics of cancer research for clinicians, research scientists and advanced students. Given the overwhelming success of the first edition, which appeared in 2001, and fast development in the different fields of cancer research, it has been decided to publish a second fully revised and expanded edition. With an A-Z format of over 7,000 entries, more than 1,000 contributing authors provide a complete reference to cancer. The merging of different basic and clinical scientific disciplines towards the common goal of fighting cancer makes such a comprehensive reference source all the more timely.
Since the publication of the first edition of Signal Transduction: A Practical Approach in 1992 there has been a great deal of new information about the processes of signal transduction and consequently many new methods have been developed. This new edition has therefore been updated and extended to include the major new methods now available. The first part of the book is mainly concerned with G protein-coupled receptors and covers structural studies of conformational changes and binding sites, phosphorylation and desensitisation, identification, receptor fusion proteins, and reporter gene systems. The second part includes methods for studying components of the other major families of signal transduction: adenylyl cylase and cAMP, phosphorylated inositol lipids, phosphinositide 3-kinases, phosphlipase D and phosphatidylcholine, sphingosine kinase, and inositol 1,4,5-triphosphate. Also included are chapters on baculoviral expression systems and the quantitative assay of mitogen activated protein kinases in intact cells and tissues. As with the previous edition Signal Transduction 2e covers a wide range of techniques and will be useful to both experienced researchers and newcomers.
Aimed at advanced undergraduates, postgraduates and researchers, this important textbook provides a detailed description of the structure and mechanisms of phosphoinositide 3-kinase (PI3Ks) signalling of all classes, with focus on the cellular context of PI3K activity, including its relevance to normal tissue and diseased states.This book contains a general review chapter detailing the mechanisms of cell proliferation and apoptosis, which are two of the main cellular targets of PI3K signalling. In addition, it provides a detailed description of the role of PI3K on the regulation of FOXO proteins, which are now becoming one of the most closely studied and important proteins in the regulation of cell death, cell proliferation and senescence./a
The 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.
This book aims to bridge the gap in understanding how protein-tyrosine phosphatases (PTPs), which carry out the reverse reaction of tyrosine phosphorylation, feature in cancer cell biology. The expertly authored chapters will first review the general features of the PTP superfamily, including their overall structure and enzymological properties; use selected examples of individual PTP superfamily members, to illustrate emerging data on the role of PTPs in cancer; and will review the current status of PTP-based drug development efforts. Protein Tyrosine Phosphatases in Cancer,from renowned researchers Benjamin Neel and Nicholas Tonks, is invaluable reading for researchers in oncology, stem cell signaling,and biochemistry.
This volume details our current understanding of the architecture and signaling capabilities of the B cell antigen receptor (BCR) in health and disease. The first chapters review new insights into the assembly of BCR components and their organization on the cell surface. Subsequent contributions focus on the molecular interactions that connect the BCR with major intracellular signaling pathways such as Ca2+ mobilization, membrane phospholipid metabolism, nuclear translocation of NF-kB or the activation of Bruton’s Tyrosine Kinase and MAP kinases. These elements orchestrate cytoplasmic and nuclear responses as well as cytoskeleton dynamics for antigen internalization. Furthermore, a key mechanism of how B cells remember their cognate antigen is discussed in detail. Altogether, the discoveries presented provide a better understanding of B cell biology and help to explain some B cell-mediated pathogenicities, like autoimmune phenomena or the formation of B cell tumors, while also paving the way for eventually combating these diseases.
From humble beginnings over 25 years ago as a lipid kinase activity associated with certain oncoproteins, PI3K (phosphoinositide 3-kinase) has been catapulted to the forefront of drug development in cancer, immunity and thrombosis, with the first clinical trials of PI3K pathway inhibitors now in progress. Here we give a brief overview of some key discoveries in the PI3K area and their impact, and include thoughts on the current state of the field, and where it could go from here
Bridging the gap between basic scientific advances and the understanding of liver disease — the extensively revised new edition of the premier text in the field. The latest edition of The Liver: Biology and Pathobiology remains a definitive volume in the field of hepatology, relating advances in biomedical sciences and engineering to understanding of liver structure, function, and disease pathology and treatment. Contributions from leading researchers examine the cell biology of the liver, the pathobiology of liver disease, the liver’s growth, regeneration, metabolic functions, and more. Now in its sixth edition, this classic text has been exhaustively revised to reflect new discoveries in biology and their influence on diagnosing, managing, and preventing liver disease. Seventy new chapters — including substantial original sections on liver cancer and groundbreaking advances that will have significant impact on hepatology — provide comprehensive, fully up-to-date coverage of both the current state and future direction of hepatology. Topics include liver RNA structure and function, gene editing, single-cell and single-molecule genomic analyses, the molecular biology of hepatitis, drug interactions and engineered drug design, and liver disease mechanisms and therapies. Edited by globally-recognized experts in the field, this authoritative volume: Relates molecular physiology to understanding disease pathology and treatment Links the science and pathology of the liver to practical clinical applications Features 16 new “Horizons” chapters that explore new and emerging science and technology Includes plentiful full-color illustrations and figures The Liver: Biology and Pathobiology, Sixth Edition is an indispensable resource for practicing and trainee hepatologists, gastroenterologists, hepatobiliary and liver transplant surgeons, and researchers and scientists in areas including hepatology, cell and molecular biology, virology, and drug metabolism.
The main source of energy for the body is glucose. Its low blood concentrations can cause seizures, loss of consciousness and death. Long lasting high glucose levels can cause blindness, renal failure, cardiac and peripheral vascular disease, and neuropathy. Blood glucose concentrations need to be maintained within narrow limits. The process of maintaining blood glucose at a steady state is called glucose homeostasis. This is achieved through a balance of the rate of consumption of dietary carbohydrates, utilization of glucose by peripheral tissues, and the loss of glucose through the kidney tubule. The liver and kidney also play a role in glucose homeostasis. This book aims to provide an overview of blood glucose levels in health and diseases.