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Recombinant human interleukin-2 became available for clinical use in the mid 1980s. Recent years have seen an enormous amount of clinical research with this cytokine and interleukin-2 has now been registered for use in a number of European countries for the treatment of metastatic renal cell carcinoma. This book is designed to provide the clinical oncologist wishing to use interleukin-2 with a basic background concerning the biology of the agent, a discussion concerning practical aspects, of its clinical use including management of toxicity and an overview of the clinical results together with a description of how this internesting cytokine might be developed in the future.
It is only during the last decade that the functions of sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, pit cells and other intrahepatic lymphocytes have been better understood. The development of methods for isolation and co-culturing various types of liver cells has established that they communicate and cooperate via secretion of various intercellular mediators. This monograph summarizes multiple data that suggest the important role of cellular cross-talk for the functions of both normal and diseased liver. Special features of the book include concise presentation of the majority of detailed data in 19 tables. Original schemes allow for the clear illustration of complicated intercellular relationships. This is the first ever presentation of the newly emerging field of liver biology, which is important for hepatic function in health and disease and opens new avenues for therapeutic interventions.
My personal history in the field of cytokines had an initial period of several years during which my student and then colleague, Werner Muller, tried in vain to attract me to them. My interest always vanished when I was confronted with complex data pointing to func tional redundancy of cytokines in cell culture systems. When gene targeting in the mouse germline became possible, this frustration came to an end. We and others immediately embarked on analyzing the in vivo function of cytokines and the problem of functional redundancy with this powerful new approach. The early cytokine gene knockouts performed by colleagues in Wiirzburg (IL-2) and by ourselves (IL-4 and IL-l 0) seemed to give clear answers and at the same time led to surprises: Each of these cytokines apparently had its own special and irreplaceable function, and this function could be quite distinct from what had been anticipated from functional experiments in vitro. Al though the latter finding is of course a wonderful incentive for fur ther research, the former is pleasing in a general sense since it highlights the value of each of those one hundred thousand genes or so in our genome, cherished by evolution to become respectable mem bers of the community. Even in the present era of "genomics" there will be no way around the careful functional analysis of each gene by itself.
This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.
Covering everything from basic science to disease-specific clinical trials, current applications and future directions, this book discusses the novel biological response modifier interleukin-2. This immunoactive therapy is designed for use in the treatment of metastatic renal cancer and, possibly, melanoma and other malignancies. Examining the value and toxic manifestations of different treatment regimens, this text: describes the biochemistry of the IL-2 receptor, the activation of natural killer cells and the lymphokine-activated killer (LAK) cell phenomenon; explicates tumour-infiltrating lymphocytes and the effect of IL-2 on in vitro assays of immune function; emphasizes high-dose IL-2 therapy in renal cell carcinoma and malignant melanoma; reviews in detail IL-2 treatment of other solid tumours and haematologic malignancies; illustrates the use of lower dose regimens, regional administration and combinations of IL-2 with other therapies; elucidates toxicities associated with IL-2, their pathogenesis and clinical management; and highlights future developments, including gene therapy and the co-administration of cytokine antagonists to reduce toxicity.
The molecular structure of interleukin-2 (IL-2) and that of its receptor subunits provide a basis for understanding lymphocyte activation by IL-2 and the generation of effector cells capable of mediating cytotoxicity towards tumors. This book provides an up-to-date account of IL-2, its effect on lymphocyte function, and clinical applications. Internationally know experts review the molecular aspects of cell signalling, giving insight on the in vivo pathways of activation likely to be important in determining clinical responses. They also examine the use of cytokines, particularly IL-2, in the treatment of cancer, and describe the results of recent clinical trials using IL-2, as well as of adoptive cell therapy. Providing a clear account of recent progress, the book also reviews the problems involved in attempting to improve the therapeutic benefit of IL-2, along with the importance of mechanisms which subverse IL-2 responses. This is the most up-to-date account of molecular research and clinical trials in this area, and will be of great benefit to students and researchers in immunology, pharmacology, biochemistry, and oncology who are interested in this vitally important topic.
Between Bench and Bedside is a compelling account of the clinical trials of interleukin-2 at a major French cancer hospital. Löwy's book offers a remarkable insider's view of the culture of clinical experimentation in oncology.
Inflammation has become one of the most exciting and rewarding areas of medical research. Recent years have seen a revolution in our understanding of how blood and tissue cells interact and of the intracellular mechanisms controlling their activation. This has revealed the underlying inflammatory pathology of many diseases and provided multiple new targets for anti-inflammatory and immunomodulatory therapy. The Encyclopedia of Inflammatory Diseases will cover the following areas: Inflammatory Processes and Cells Inflammatory Diseases Mediators of Inflammation Pharmacology of Inflammation Since inflammatory diseases and their therapy cover a broad range of scientific and medical fields, the encyclopedia will be co-edited by four international experts, a clinician and three researchers from the disciplines of immunology, biochemistry, and pharmacology, in this way providing students, basic and clinical scientists and practitioners in academia, hospitals and industry with valuable interlinked information. This living project will serve as a reliable and comprehensive data pool for everybody working in inflammation research. Owing to its dynamic nature, it will grow with time and future editions, becoming an indispensible source of information for academia, clinical practitioners and industry.