Several fundamentally important questions form the basis for this book. What are the relationships between tumour formation and tumour pH? What are the effects of tumour pH and hypoxia on carcinogenesis or tumorigenesis? What are the therapeutic consequences of tumour pH? It is hypothesised that low extracellular pH is not only an important consequence of tumour growth but may also promote further tumorigenic transformation. Furthermore, in vitro studies suggest that low pH strongly affects the efficacy of chemo- and radiotherapy. Better understanding of the influence of pH on tumour growth, coupled with manipulation of the pH of the tumour microenvironment, may lead to the development of more effective therapies.
This volume provides a detailed overview of the mechanisms by which steroid hormones regulate gene activity in target cells. It should be of interest to molecular biologists, endocrinologists, pharmacologists and clinicians interested in gene regulation hormones and steroid antagonists.
Receptor Tyrosine Kinase: Structure, Functions and Role in Human Disease, for the first time, systematically covers the shared structural and functional features of the RTK family. Receptor Tyrosine Kinases (RTKs) play critical roles in embryogenesis, normal physiology and several diseases. And over the last decade they have become the Number 1 targets of cancer drugs. To be able to conduct fundamental research or to attempt to develop pharmacological agents able to enhance or intercept them, it is essential first to understand the evolutionary origin of the 58 RTKs and their roles in invertebrates and in humans, as well as downstream signaling pathways. The assembly of chapters is written by experts and underscores commonalities between and among the RTKs. It is an ideal companion volume to The Receptor Tyrosine Kinase: Families and Subfamilies, which proceeds, family by family through all of the specific subfamilies of RTKs, along with their unique landmarks.
The extracellular matrix (ECM) is an acellular three-dimensional network composed of proteins, glycoproteins, proteoglycans and exopolysaccharides. It primarily serves as a structural component in the tissues and organs of plants and animals, or forms biofilms in which bacterial cells are embedded. ECMs are highly dynamic structures that undergo continuous remodeling, and disruptions are frequently the result of pathological processes associated with severe diseases such as arteriosclerosis, neurodegenerative illness or cancer. In turn, bacterial biofilms are a source of concern for human health, as they are associated with resistance to antibiotics. Although exopolysaccharides are crucial for ECM formation and function, they have received considerably little attention to date. The respective chapters of this book comprehensively address such issues, and provide reviews on the structural, biochemical, molecular and biophysical properties of exopolysaccharides. These components are abundantly produced by virtually all taxa including bacteria, algae, plants, fungi, invertebrates and vertebrates. They include long unbranched homopolymers (cellulose, chitin/chitosan), linear copolymers (alginate, agarose), peptoglycans such as murein, heteropolymers like a variety of glycosaminoglycans (hyaluronan, dermatan, keratin, heparin, Pel), and branched heteropolymers such as pectin and hemicellulose. A separate chapter is dedicated to modern industrial and biomedical applications of exopolysaccharides and polysaccharide-based biocomposites. Their unique chemical, physical and mechanical properties have attracted considerable interest, inspired basic and applied research, and have already been harnessed to form structural biocomposite hybrids for tailor-made applications in regenerative medicine, bioengineering and biosensor design. Given its scope, this book provides a substantial source of basic and applied information for a wide range of scientists, as well as valuable textbook for graduate and advanced undergraduate students.
This is the first volume in an interdisciplinary three-book series covering the full range of biological, clinical, and surgical aspects in the evaluation, diagnosis, and treatment of patients with craniofacial malformations. This volume opens by considering general topics such as developmental biology and disease classification and then examines in depth the biological basis of the various malformations, including craniosynostoses, cleft-lip and palate with complex orofacial clefts, branchio-oculo-facial syndromes, rare syndromes, soft tissue malformations, and dysgnathia. Psychological aspects, including psychological evaluation methods and therapies and quality of life issues, are then addressed. Finally, all relevant clinical, radiological, and genetic investigations are described and important diagnostic issues are explored. Featuring numerous high-quality illustrations, the book will be of high value for all clinicians, researchers, and postgraduate students who deal with these malformations. The accompanying two volumes describe treatment principles and present in an atlas manner all relevant surgical techniques in detail. The content of this multivolume set, written by the world’s leading research and clinical specialists in their discipline, represents therefore the recent intellect, experience, and state of this medical field.
Liver Immunology: Principles and Practice, Second Edition begins with important information about the epidemiology and mortality of liver disease worldwide. This information is followed by chapters related to basic immunology, application of liver immunology for diagnosis, and several excellent chapters that provide a solid foundation for understanding immune-mediated liver disease, including those associated with the biliary tree. A chapter on non-hepatic manifestations of immune mediated liver disease helps provide context for how these diseases affect the patient overall. In addition, chapters discuss various discrete immunologically-mediated infectious liver disorders including those related to bacteria, parasites, and all of the classic viruses. Chapters on the traditional autoimmune liver diseases -- primary biliary cirrhosis, autoimmune hepatitis, primary sclerosing cholangitis as well as overlap syndrome – are also included. The breadth of this comprehensive second edition is highlighted by chapters on alcoholic liver disease, non-alcoholic fatty liver disease, and drug-induced liver disease, among others. This invaluable new edition ends with a forward-looking view of future directions and how the field might meet the challenge of refractory patients. Developed by a renowned group of authors, Liver Immunology: Principles and Practice, Second Edition will again serve as a comprehensive textbook by providing an excellent overview for this rapidly evolving field. It greatly adds to the understanding of the pathogenesis of these diseases, while also providing novel insights that can be harnessed into helping improve the care of patients afflicted with various immune-mediated diseases. This volume will again be a must-read for clinicians at all levels, investigators and students.
Anoikis is defined broadly as apoptosis that is inhibited by appropriate cell-matrix interactions. Normal and tumor cells vary widely in their sensitivity to anoikis, but, in general, metastatic tumor cells are inevitably anoikis-resistant. In particular, tumor cells that possess a cancer stem cell or mesenchymal phenotype, arising from the oncogenic Epithelial-Mesenchymal Transition (EMT), are transcriptionally re-programmed to resist anoikis. While the anoikis response occurs through the mitochondrial pathway typically found in other apoptotic responses (e.g., DNA damage, death receptors, oxidative stress), the regulation of anoikis by cell-matrix signalling is unique and only partially characterized. The uniqueness of anoikis is: a. regulation by integrins, non-integrin matrix receptors, and the signaling complexes associated with them; b. regulation by metabolic changes occurring in response to attachment/detachment; c. regulation by oncogenes and tumor suppressor genes d. regulation by tumor microenvironment; e. regulation by EMT.
Human skin cancers, the most common type of tumors, represent a significant health burden. The deadliest is unquestionably melanoma. Half of melanomas have an activating mutation in the BRAF gene, prompting development of novel drugs, vemurafenib and dabrafenib, specifically targeting mutated BRAF. Trametinib and cobimetinib, which block MEK, a BRAF effector protein, have been used in combination with BRAF inhibitors. A promising new melanoma treatment is immunotherapy, approach that boosts patient's own immune system to attack cancer. Pembrolizumab and nivolumab inhibit PD-1, whereas Ipilimumab targets CTLA-4, another immunity check point, to boost the immune response. Here we focus on pathways, mechanisms, targets and treatments of human skin cancers, with particular emphasis on the new developments in the research on melanomas.
Epigenetics and Metabolomics, a new volume in the Translational Epigenetics series, offers a synthesized discussion of epigenetic control of metabolic activity, and systems-based approaches for better understanding these mechanisms. Over a dozen chapter authors provide an overview of epigenetics in translational medicine and metabolomics techniques, followed by analyses of epigenetic and metabolomic linkage mechanisms likely to result in effective identification of disease biomarkers, as well as new therapies targeting the removal of the inappropriate epigenetic alterations. Epigenetic interventions in cancer, brain damage, and neuroendocrine disease, among other disorders, are discussed in-depth, with an emphasis on exploring next steps for clinical translation and personalized healthcare. - Offers a synthesized discussion of epigenetic regulation of metabolic activity and systems-based approaches to power new research - Discusses epigenetic control of metabolic pathways and possible therapeutic targets for cancer, neurodegenerative, and neuroendocrine diseases, among others - Provides guidance in epigenomics and metabolomic research methodology
Handbook of Cell Signaling, Three-Volume Set, 2e, is a comprehensive work covering all aspects of intracellular signal processing, including extra/intracellular membrane receptors, signal transduction, gene expression/translation, and cellular/organotypic signal responses. The second edition is an up-to-date, expanded reference with each section edited by a recognized expert in the field. Tabular and well illustrated, the Handbook will serve as an in-depth reference for this complex and evolving field. Handbook of Cell Signaling, 2/e will appeal to a broad, cross-disciplinary audience interested in the structure, biochemistry, molecular biology and pathology of cellular effectors. - Contains over 350 chapters of comprehensive coverage on cell signaling - Includes discussion on topics from ligand/receptor interactions to organ/organism responses - Provides user-friendly, well-illustrated, reputable content by experts in the field
