One of the most exciting areas of cancer research now is the development of agents which can target signal transduction pathways that are activated inappropriately in malignant cells. The understanding of the molecular abnormalities which distinguish malignant cells from their normal counterparts has grown tremendously. This volume summarizes the current research on the role that signal transduction pathways play in the pathogenesis of cancer and how this knowledge may be used to develop the next generation of more effective and less toxic anticancer agents. Series Editor comments: "The biologic behavior of both normal and cancer cells is determined by critical signal transduction pathways. This text provides a comprehensive review of the field. Leading investigators discuss key molecules that may prove to be important diagnostic and/or therapeutic targets."

CD4+FoxP3+ regulatory T cells (Tregs) play an indispensable role in the maintenance of immune homeostasis and prevention of autoimmune diseases, and represent a major cellular mechanism of tumor immune evasion. Targeting of Tregs has great potential in the treatment of some major human diseases, including autoimmunity, transplant rejection, GvHD, and cancer, and are critical controllers of immunity to infectious pathogens. It is expected they will also be central to the control of allergic and inflammatory diseases. Understanding the biological pathways crucial for the regulation of Treg activity is a prerequisite for harnessing the immense therapeutic potential of Tregs. TNF is generally believed to be a master pro-inflammatory cytokine, and anti-TNF therapy has become a mainstay treatment for some autoimmune diseases. However, experimental evidence indicates that TNF preferentially activates Tregs, resulting in the expansive proliferation, phenotypic stability, and enhanced suppressive capacity of these immune suppressors. This effect of TNF is mediated by TNFR2, which is preferentially expressed by human and mouse Tregs. Furthermore, expression of TNFR2 is able to identify the most suppressive subset of Tregs. Although counterintuitive and contradictory to earlier reports, these findings have been supported by increasing experimental evidence from both human and mouse studies. These recent studies revealing the Treg-promoting effect of TNF not only leads to the redefinition of the immunological biology of this pleiotropic cytokine, they are also helpful in designing novel therapies in the treatment of cancer, autoimmune diseases, and GvHD, as well as enhancing current vaccines and immunomodulators. In this article collection, current knowledge on the cellular and molecular aspects of the Treg-stimulatory effect of the TNF-TNFR2 pathway will be discussed. An insight of the physiological and pathological roles of such effects of TNF in an inflammatory reaction and immune response will be provided. The seemingly contradictory Treg-promoting effect of TNF and immunosuppressive effect of anti-TNF therapy will be analyzed. Recent efforts to translate such discoveries into therapeutic benefits will be introduced. The novel strategies in the treatment of cancer and GvHD, by down- or up-regulation of Treg activity through targeting TNFR2, will be highlighted. In addition to Tregs, TNFR2 has also been found to play a key role in the accumulation and immunosuppressive function of myeloid-derived suppressive cells (MDSCs) and Mesenchymal stem cells (MSCs). Therefore, the current understanding of the role of TNF-TNFR2 signal in other type of immunosuppressive cells, as well as its clinical and therapeutic implications, have also been considered.

This volume explores some of the most exciting recent advances in basic research on animal models of molecular pathology. - This series provides a forum for discussion of new discoveries, approaches, and ideas - Contributions from leading scholars and industry experts - Reference guide for researchers involved in molecular biology and related fields

Over two billion people worldwide are at risk for the spectrum of disorders known as "The Iodine Deficiency Disorders." 1-10% will suffer cretinism; 5-30% will have some sort of brain damage or neurological impairment and 30-70% will be hypothyroid. The causes of iodine deficiencies can be considered from both simplistic and more complex perspectives: From the leaching of iodine from soil resulting in crops with low iodine content to malnutrition resulting in impaired iodine absorption. Poor dietary diversification and impoverished socio-economic development can also lead to iodine deficiencies. Although it is possible to diagnose and treat deficiencies, there is still an ongoing dialogue regarding the detailed molecular pathology of iodine homeostatis, how hypothyroidism impacts the body tissues, and efficient diagnosis and treatment of the Iodine Deficiency Disorders. This Handbook provides a resource of information on the various pathways and processes based on different countries or diseases. Because there is a constant flow of new information on iodine and related disorders, the goal of this Handbook is to provide a base of scientific information upon which additional knowledge can be applied. - Provides important information on one of the most common micro-nutrient deficiencies in the world, the most important "single nutrient-multiple consequences" paradigm today - Includes information on iodine-related diseases, including those that are common, preventable and treatable - Provides insight from a broad perspective of viewpoints -- from subcellular transports to economic impact

The human hypothalamus, a small structure at the base of the brain, has strategic importance for the harmonic function of the human body. It controls the autonomic nervous system, neuroendocrine function, circadian and circannual rhythms, somatic activities, and behavior, and is situated at the borders between the brain and the body and the brain and the soul, meeting points for mind and body. The hypothalamus is involved in a wide range of higher mental functions, including attention, learning and reinforcement of mnemonic processes, emotional control, mood stability, and cognitive-emotional interactions. It also has a role to play in behavioral disorders, panic reactions, cluster headache, gelastic epilepsy, mental deficiency, periodic disorders, depression, autism, and schizophrenia, and in a substantial number of neurodegenerative diseases. It enlarges greatly the dimensions of the hypothalamic contribution in controlling psychosomatic equilibrium and retaining internal unity of the human existence.

The results of randomized trials evaluating the use of early or adjuvant systemic treatment for patients with resectable breast cancer provide an eloquent rebuttal to those who would argue that we have made no progress in the treatment of cancer. Many of the tumors that we have been most successful in curing with chemotherapy and other newer forms of treatment are relatively uncommon. In contrast, breast cancer continues to be the single most common malignancy among women in the western world, is increasingly a cause of death throughout Asia and Third-World countries, and remains one of the most substantial causes of cancer mortality world wide. The use of mammography as a means of early detection has been shown to reduce breast cancer mortality by 25-35% among those popu lations in which it is utilized. The use of adjuvant systemic treatment in appropriate patients provides a similar (and additional) reduction in breast cancer mortality. Few subjects have been so systematically studied in the history of medicine, and it seems fair to conclude that the value to adjuvant systemic therapy in prolonging the lives of women with breast cancer is more firmly supported by empirical evidence than even the more conventional or primary treatments using various combinations ofsurgery and radiotherapy.

The third book in the group devoted to the "natural" immune system, this volume provides the ideal detailed, up-to-date overview of neutrophil function. Distilling new information alongside observations of the past, the book focuses on some of the most critical developments in currentneutrophil research. Specific examples of diseases resulting from neutrophil dysfunction and deficiency are brought to life by clinical case studies. An essential source of current research into this exciting field, this volume will be invaluable for advanced students and researchers in immunology,cell biology, and medicine.