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Diabetes mellitus is a complex, multifactorial disease that is often associated with progressive retinopathy and visual loss. In this book, Drs. Scott, Flynn, and Smiddy have compiled the current basic science and clinical information from leading authorities on diabetic eye disease. They have also included the results of clinical trials in patients with diabetic retinopathy, as well as the guidelines established by collaborative studies and the concepts of disease mechanisms and clinical management that have subsequently evolved from those guidelines. This monograph will provide practitioners with a concise, up-to-date, practical reference for the diagnosis and management of ocular disease in diabetic patients.
The field of antibody engineering has become a vital and integral part of making new, improved next generation therapeutic monoclonal antibodies, of which there are currently more than 300 in clinical trials across several therapeutic areas. Therapeutic antibody engineering examines all aspects of engineering monoclonal antibodies and analyses the effect that various genetic engineering approaches will have on future candidates. Chapters in the first part of the book provide an introduction to monoclonal antibodies, their discovery and development and the fundamental technologies used in their production. Following chapters cover a number of specific issues relating to different aspects of antibody engineering, including variable chain engineering, targets and mechanisms of action, classes of antibody and the use of antibody fragments, among many other topics. The last part of the book examines development issues, the interaction of human IgGs with non-human systems, and cell line development, before a conclusion looking at future issues affecting the field of therapeutic antibody engineering. - Goes beyond the standard engineering issues covered by most books and delves into structure-function relationships - Integration of knowledge across all areas of antibody engineering, development, and marketing - Discusses how current and future genetic engineering of cell lines will pave the way for much higher productivity
Advances in Cancer Research, volume 153 provides a timely review of the biology, biochemistry, and current approaches to therapeutically target the RAS oncoprotein, the most frequently mutated oncogene family in human cancers. 2021 saw the approval of the first direct RAS inhibitor (sotorasib) for use in treating non-small cell lung cancers harboring KRAS(G12C) mutations. The successful approval and use of this drug highlights that the once "undruggable RAS is indeed pharmacologically tractable. This volume provides an overview of efforts to develop additional approaches to therapeutically target oncogenic RAS. In addition, the reader will find excellent reviews on the history and research efforts to understand the biochemistry and oncogenic activity of RAS in human cancers. - Overview of the history and development of efforts to pharmacologically inhibit RAS. - Discussion of the biochemistry and biology of different RAS mutant proteins and how this might be effectively leveraged in the development of anti-RAS therapies. - Up-to-date reviews of the cutting-edge approaches to develop new anti-RAS pharmacologics.
This book presents a contemporary review of the field of Pain Therapeutics, including the historical medicines which still dominate standard of care treatments, as well as the new mechanisms and combinations/reformulations that have dominated the regulatory approvals over the last decade. In addition this book provides a deep review of the key biological mechanisms currently under investigation for their utility into the treatment of pain, such as ion channels, opiates and others. Additional discussion highlights the current challenges of pain research, covering a range of topics from difficulties in identifying new targets from pre-clinical models to the current regulatory and commercial challenges. This background sets the scene for recent scientific changes in pain research, such as the drive for genetic validation of targets and the derivation of human cell platforms from stem cells. Finally the book covers the discovery and development stories for two pain products approved in the last decade. These case studies for Lyrica and the Butrans patch, give insight into the discovery and development challenges and successes for both an oral and non-oral product.
Psychiatry: Past, Present, and Prospect provides a set of perspectives written in essay form from eminent contributors, covering the major developments in psychiatry over the last 40 years.
Perspectives on Occupational Therapy Education: Past, Present, and Future outlines a path forward for occupational therapy educators, incorporating the impact of historical context, contemporary issues and trends, and international viewpoints on the development of the profession. With this mission in mind, Drs. Steven D. Taff, Lenin C. Grajo, and Barbara R. Hooper offer helpful tips, practical tools, and fresh insights to support current and future educators in developing their teaching philosophies and pedagogies.
Historically, the first observation of a transmissible lytic agent that is specifically active against a bacterium (Bacillus anthracis) was by a Russian microbiologist Nikolay Gamaleya in 1898. At that time, however, it was too early to make a connection to another discovery made by Dmitri Ivanovsky in 1892 and Martinus Beijerinck in 1898 on a non-bacterial pathogen infecting tobacco plants. Thus the viral world was discovered in two of the three domains of life, and our current understanding is that viruses represent the most abundant biological entities on the planet. The potential of bacteriophages for infection treatment have been recognized after the discoveries by Frederick Twort and Felix d’Hérelle in 1915 and 1917. Subsequent phage therapy developments, however, have been overshadowed by the remarkable success of antibiotics in infection control and treatment, and phage therapy research and development persisted mostly in the former Soviet Union countries, Russia and Georgia, as well as in France and Poland. The dramatic rise of antibiotic resistance and especially of multi-drug resistance among human and animal bacterial pathogens, however, challenged the position of antibiotics as a single most important pillar for infection control and treatment. Thus there is a renewed interest in phage therapy as a possible additive/alternative therapy, especially for the infections that resist routine antibiotic treatment. The basis for the revival of phage therapy is affected by a number of issues that need to be resolved before it can enter the arena, which is traditionally reserved for antibiotics. Probably the most important is the regulatory issue: How should phage therapy be regulated? Similarly to drugs? Then the co-evolving nature of phage-bacterial host relationship will be a major hurdle for the production of consistent phage formulae. Or should we resort to the phage products such as lysins and the corresponding engineered versions in order to have accurate and consistent delivery doses? We still have very limited knowledge about the pharmacodynamics of phage therapy. More data, obtained in animal models, are necessary to evaluate the phage therapy efficiency compared, for example, to antibiotics. Another aspect is the safety of phage therapy. How do phages interact with the immune system and to what costs, or benefits? What are the risks, in the course of phage therapy, of transduction of undesirable properties such as virulence or antibiotic resistance genes? How frequent is the development of bacterial host resistance during phage therapy? Understanding these and many other aspects of phage therapy, basic and applied, is the main subject of this Topic.
Haematopoietic stem cell transplantation was initiated in the early 1970’s by pioneers studying radiation-induced bone marrow damage and blood transfusion. Since that time there have been over one million transplants and over 34 million donors registered with the world marrow donor association. This special edition of Frontiers in Immunology highlights the research achievements which led to the curative therapy of haematopoietic stem cell transplantation (HSCT) but also reviews the ongoing complications such as graft versus host disease (GvHD) and infection caused by the procedure. Early animal and human studies are reviewed as well as those which led to the development of changes in transplant protocols such as peripheral blood stem cell and cord blood transplants and the harnessing of graft versus leukaemia (GvL) effects by donor lymphocyte infusions. The eBook covers immunogenetics, the role of biomarkers, and future developments of the therapy which will aim to further improve the outcome for HSCT patients. The eBook is divided into 8 chapters dealing with animal studies; a history of early human studies; the pathophysiology of HSCT; graft versus host disease; graft versus leukaemia effects; immune reconstitution; non-HLA immunogenetics and future developments, including use of mesenchymal stem cells, virus specific T cells and chimeric antigen receptor (CAR) therapy.
This book describes the challenges involved in developing mTOR inhibitors for cancer treatment, starting with an in-depth examination of their molecular mechanism of action, with emphasis on the class side-effects, efficacy and mechanisms of resistance, as well as on promising novel directions for their development, including novel compounds and rational combinations with other anti-neoplastic drugs. Over the last 10 years, inhibitors of mTOR have emerged as a major class of anticancer drugs. Two rapamycin analogs are currently approved for the treatment of renal cell carcinoma, and it is estimated that a variety of other tumor types could benefit from mTOR inhibition, with numerous clinical trials (including pivotal registration trials) already underway. Second-generation small-molecule inhibitors of the pathway have also shown promise in terms of their superior tolerability and efficacy and are undergoing extensive clinical evaluation, with an estimated 30+ compounds currently under evaluation.