Protein kinase CK2 (formerly casein kinase II or 2) is known to play a critical role in the control of cell growth and cell death and is thus intimately involved in the development of cancer. More specifically, CK2 has been found to be elevated in all cancers examined. While CK2 levels are known to be high in proliferating normal cells, CK2 has also been found to be a potent suppressor of apoptosis and is a link to the cancer cell phenotype, which is characterized by deregulation of both cell proliferation and cell death. Indeed, it would appear that CK2 impacts many of the hallmarks of cancer and it has now gained considerable attention as a potential target for cancer therapy. Protein Kinase CK2 and Cellular Function in Normal and Disease States increases knowledge of the role of CK2 in the development of cellular dysfunction and emphasizes that this protein may serve as a target of drug development for improved cancer therapy. In addition, it is a handy tool that provides cancer researchers, graduate students, and all scientists involved in CK2 research with one main source for the latest advances in CK2 research.
This book is a printed edition of the Special Issue "An Updated View on an Emerging Target: Selected Papers from the 8th International Conference on Protein Kinase CK2" that was published in Pharmaceuticals
This book reviews the principles of design and examples of successful implementation of proteinkinase inhibitors (PKI), and offers a comprehensive and authoritative overview of the history and latest developments in the field. Chapters written by experts from industry and academia cover the function, structure and topology of Proteinkinases, molecular modelling, disclose how to achieve high level of selectivity for kinase inhibitors, and exploit kinase inhibitors for cancer treatment. Particular attention is given to Inhibitors of c-Jun N-terminal kinase 3, and to covalent Janus Kinase 3 Inhibitors. A case study on Receptor Tyrosine Kinases EGFR, VEGFR, PDGFR is also presented in this book. Given its breath, this book will appeal to medicinal chemists, students, researchers and professionals alike.
This book, now in an extensively revised second edition, describes the crucial role of zinc signaling in biological processes on a molecular and physiological basis. Global leaders in the field review the latest knowledge, including the very significant advances in understanding that have been achieved since publication of the first edition. Detailed information is provided on all the essentials of zinc signaling, covering molecular aspects and the roles of zinc transporters, the zinc sensing receptor, and metallothioneins. Detection techniques for zinc signals, involving genetically encoded and chemical probes, are also described. The critical contributions of the zinc signal in maintaining health and the adverse consequences of any imbalance in the signal are then thoroughly addressed. Here, readers will find up-to-date information on the significance of the zinc signal in a wide range of conditions, including cardiovascular disorders, neurodegenerative diseases, diabetes, autoimmune diseases, inflammatory conditions, skin disease, osteoarthritis, and cancer. The book will be of value for researchers, clinicians, and advanced students.
The unique biology of cardiac fibroblasts and related cells, such as cardiac myofibroblasts and valvular interstitial cells, distinguish them from other fibroblastic cells, a concept that is only beginning to be widely appreciated. Further, the natural signals that stimulate and inhibit cardiac fibrosis within these cells are not well understood. This volume compiles articles that address the molecular mechanisms that control the synthesis and secretion of the cardiac ECM. The book showcases chapters that highlight discussion of role of Transforming Growth Factor β (TGFβ), an important fibrogenic cytokine and its downstream effectors SMAD in many cardiac diseases. Further, the contributions highlight information to discuss endogenous inhibitors of cardiac fibrosis, as well as advances in tissue engineering specific to matrix in the heart. Finally, discussions of unifying mechanisms of matrix remodeling in valves and myocardium are presented. The mechanisms involved in the stimulation of cardiac fibrosis are not fully understood. In most cases the marginal attenuation of cardiac fibrosis as a result of a given therapy is a beneficial side-effect linked to other primary effects on other cells, especially cardiomyocytes. Very few drugs or agents are known to affect the function and dysfunction of cardiac fibroblasts and myofibroblasts alone. The book helps to translate the information gathered within to allow us to alter the course of fibrogenic events that are typical of cardiac fibrosis, and thereby reduce their burden on the patient and on society itself.
This book intends to bring together, a panel of renowned experts in the field of vascular biology and diabetology, to integrate the current understanding of the pathogenesis and pathophysiology of vascular diseases in diabetes mellitus. This attempt is significant given the increasing interest in this area as the prevalence of vascular diseases continues to escalate globally. Patients with diabetes are at a higher risk of structural and functional changes in all vessel walls of the human body. Vascular complications of diabetes are leading causes for both morbidity and mortality. In recent years, several articles have focused on advancing our knowledge on the profound effect of hyperglycemia and insulin resistance on building up vascular wall inflammation leading to endothelial dysfunction in patients with diabetes mellitus Other reports have elaborated on the various disorders, hyperglycemia can lead to, their therapies, adverse effects and complications. There are also studies that highlight the role of factors that induce vascular wall alterations in hyperglycemia. In this book, we attempt to discuss vascular disease progression in diabetes with a unique approach. We attempt to provide a complete perspective of the pathophysiology of vascular complications and then dissect each of the factors that play a key role in accelerating vascular wall alterations in diabetes. Each of these factors has been adversely implicated in the initiation and progression of disease to a large extent. In this collection for the first time all these factors would be described under a common canopy. Further, the text would emphasize on pathogenesis of micro vascular complications of diabetes, such as retinopathy, neuropathy and nephropathy. Pharmacological therapies for treating vascular dysfunction in diabetes mellitus would also be reviewed. This compendium hopefully would be an invaluable replacement to scores of literature on diabetic vascular disease and would be of great interest to clinicians, academicians, medical students and researchers. The book will be divided into seven sections, each emphasizing a common incentive to development of vascular disease in diabetes. Section I deals with pathophysiology of diabetic vascular disease, beginning with an update on the global burden of diabetes mellitus and its vascular complications. The pathophysiology and pathogenesis of diabetes associated macrovasculopathy, how hyperglycemia functions as an atherogenic factor, effects of hyperglycemia on smooth muscle accumulation in vascular lesions and genetic susceptibility for increased risk of vascular disease in diabetes will be discussed in the following chapters of this section. The next section (Section II) surveys the process of endothelial dysfunction under hyperglycaemia and hyperinsulinemia and their effects on angiogenesis, vascular remodeling and wound healing. A chapter is also dedicated to the endothelial progenitor cell population and its dysfunction during development of vascular complications in diabetes. Section III will highlight the molecular mechanisms underlying endothelial dysfunction, various pathways such as nitric oxide synthase pathway, oxidative stress pathway, renin – angiotensin system and increased vascular superoxide production in the initiation and progression of vascular disease in diabetes. This section also covers role of endothelin, monocyte derived cytokines, peroxynitrate and adipokines in macrovascular complications of diabetes. Metabolic factors such as advanced glycation end products, atherogenic dyslipoproteinaemia, and homocysteine will be reviewed in Section IV, whereas an overview of the hemostatic factors such as platelet dysfunction, hyperglycaemia induced thrombin formation and aberrant clot lysis will be dwelled upon in Section V.Section VI includes chapters on microvascular complications of diabetes which encompasses long term complications of diabetes affecting small blood vessels of the eye, kidneys and nervous system. The pathogenesis and mechanisms of these complications would be detailed here. The final section (Section VII) of the book will consider mechanism of action of drugs for treating endothelial dysfunction in diabetes mellitus which would elaborate on lipid regulating therapies such as statins, as well as other therapies such as ACE inhibitors, Angiotensin II receptors, insulin, metformin and their effects on enhancing vascular function in diabetes.“/div>divWe intend to invite authors who symbolize a multidisciplinary approach to this complicated disease. The proposed authors include clinicians who understand the trend of vascular complications in their long term clientele, epidemiologists with a holistic view, basic and experimental researchers with years of experience in dissecting the factors leading to endothelial dysfunction and clinical researchers with the skill of translating bench work to the bedside. We expect this book will be of significant value and interest to the same group of clinicians, researchers, post doctoral fellows and medical and non medical graduate students. The novel assimilated insights could stimulate development of mechanism based prevention and therapeutic strategies providing a promising option to limit cardiovascular complications in diabetes mellitus.
Na+-K+ ATPase or Na-pump ATPase, a member of “P”-type ATPase superfamily, is characterized by association of multiple isoforms mainly of it’s α- and β- subunits. At present four different α- (α-1,α-2,α-3 and α-4) and three β- (β-1, β-2, and β-3) isoforms have been identified in mammalian cells and their differential expressions are tissue specific. Regulation of Na+-K+ ATPase activity is an important but a complex process, which involves short-term and long-term mechanisms. Short-term regulation of Na+-K+ ATPase is either mediated by changes in intracellular Na+ concentrations that directly affect the Na+-pump activity or by phosphorylation/dephosphorylation-mediated by some stimulants leading to changes in its expression and transport properties. On the other hand, long-term regulation of Na+-K+ ATPase is mediated by hormones, such as mineralocorticoids and thyroid hormones, which cause changes in the transcription of genes of α- and β- subunits leading to an increased expression in the level of Na+-pump. Several studies have revealed a relatively new type of regulation that involves the association of small, single span membrane proteins with this enzyme. These proteins belong to the FXYD family, the members of which share a common signature sequence encompassing the transmembra ne domain adjacent to the isoform(s) of α-β subunits of Na+-K+ ATPase. Considering the extraordinary importance of Na+-K+ ATPase in cellular function, several internationally established investigators have contributed their articles in the monograph entitled “Regulation of Membrane Na+-K+ ATPase” for inspiring young scientists and graduate students to enrich their knowledge on the enzyme, and we are sure that this book will soon be considered as a comprehensive scientific literature in the area of Na+-K+ ATPase regulation in health and disease.
This book covers the latest developments in the therapeutic implications of angiogenesis, ranging from angiogenesis in the brain, angiogenesis in cancer, angiogenesis’ role in atherosclerosis and heart disease as well as metabolic disorders and peripheral vascular disease. The book is comprehensive in its coverage of angiogenesis in a diverse set of diseases and examines the role of cellular and subcellular structures during the development of angiogenesis. Well-organized and thorough, this is an ideal book for researchers and biomedical engineers working in the field of therapeutic implications of angiogenesis. This book also: Covers the basics of the physiology of angiogenesis, including VEGF pathways in angiogenesis, integr ins in angiogenesis, angiogenesis and exercise physiology, and more Details the role of angiogenesis in atherosclerosis and heart disease, including vascular endothelial growth factor and atherosclerotic plaque progression as well as angiogenesis and heart failure Illustrates in detail brain angiogenesis after stroke and the relationship between angiogenesis and Alzheimer's disease
