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The Eighth International Conference of the Inflammation Research Association was held on October 27 to 31, 1996 at Hershey Lodge and Convention Center in Hershey, Pennsylvania. As have others in this series, the conference focused on understanding the molecular mechanisms involved in acute and chronic inflammatory reactions as well as on therapeutic approaches to treating inflammatory diseases. One outstanding symposium focused on new drugs and was de signed as a forum for the dissemination of early clinical results on new anti-inflammatory agents. Other symposia spotlighted exciting advances being made in defining intracellular signaling path ways and the potential for future therapeutics that target cytokines and costimulatory pathways. This conference was characterized by a high level of participation by attendees, who represent both the academic and industrial sectors. It was gratifying to note that a large proportion of the attending scientists presented their latest findings during workshops, poster discussions, and pos ter se.ssions. This volume covers many of the highlights of the Eighth International Conference and should become a valuable resource for scientists involved in inflammation research and drug discovery.
Humans coexist with millions of harmless microorganisms, but emerging diseases, resistance to antibiotics, and the threat of bioterrorism are forcing scientists to look for new ways to confront the microbes that do pose a danger. This report identifies innovative approaches to the development of antimicrobial drugs and vaccines based on a greater understanding of how the human immune system interacts with both good and bad microbes. The report concludes that the development of a single superdrug to fight all infectious agents is unrealistic.
The immune system detects "danger" through a series of what we call pathogen-associated molecular patterns (PAMPs) or damage-associated molecular pattern molecules (DAMPs), working in concert with both positive and negative signals derived from other tissues. PAMPs are molecules associated with groups of pathogens that are small molecular motifs conserved within a class of microbes. They are recognized by Toll-like receptors (TLRs) and other pattern recognition receptors. A vast array of different types of molecules can serve as PAMPs, including glycans and glycoconjugates. Bacterial lipopolysaccharides (LPSs), endotoxins found on the cell membranes of Gram-negative bacteria, are considered to be the prototypical class of PAMPs. LPSs are specifically recognized by TLR4, a recognition receptor of the innate immune system. Other PAMPs include bacterial flagellin (recognized by TLR5), lipoteichoic acid from Gram-positive bacteria, peptidoglycan, and nucleic acid variants normally associated with viruses, such as double-stranded RNA, recognized by TLR3 or unmethylated CpG motifs, recognized by TLR9. DAMPs, also known as alarmins, are molecules released by stressed cells undergoing necrosis that act as endogenous danger signals to promote and exacerbate the immune and inflammatory response. DAMPs vary greatly depending on the type of cell (epithelial, mesenchymal, etc.) and injured tissue. Some endogenous danger signals include heat-shock proteins, HMGB1 (high-mobility group box 1), reactive oxygen intermediates, extracellular matrix breakdown products such as hyaluronan fragments, neuromediators, and cytokines like the interferons (IFNs). Non-protein DAMPs include ATP, uric acid, heparin sulfate, and DNA. Furthermore, accumulating evidence supports correlation between alarmins and changes in the microbiome. Increased serum or plasma levels of these DAMPs have been associated with many inflammatory diseases, including gastric and intestinal inflammatory diseases, graft-versus-host disease (GVHD), sepsis and multiple organ failure, allergies particularly in the lungs, atherosclerosis, age-associated insulin resistance, arthritis, lupus, neuro-inflammation/degeneration and more recently in tumors, which is particularly interesting with the emergence of immunotherapies. Therapeutic strategies are being developed to modulate the expression of these DAMPs for the treatment of these diseases. A vast number of reviews have already been published in this area; thus, in an effort to not duplicate what has already been written, we will focus on recent discoveries particularly in disease models that are epidemic in Western society: intestinal chronic inflammatory diseases including GVHD and its relationship with the microbiome, chronic infectious diseases, allergies, autoimmune diseases, neuroinflammation and cancers. We will also focus on the basic cellular roles of macrophages, T cells and B cells. This research topic brings together sixteen articles that provide novel insights into the mechanisms of action of DAMPS/alarmins and their regulation and subsequent immunologically driven responses.
Therapeutic Application of Nitric Oxide in Cancer and Inflammatory Disorders presents updated reviews on the chemistry, signaling, pre-clinical and clinical activities on the role of nitric oxide donors/inhibitors used alone and in combination with other therapeutic agents for the treatment of a variety of diseases. This book examines various studies related to the application of novel therapeutic NO (donors/inhibitors) compounds in the treatment of various cancers. These studies have been shown to exert significant therapeutic activities against various cancers and various inflammatory diseases such as rheumatoid arthritis, Crohn’s disease, allergies, and asthma, where no current effective therapies exist. Pathologies based on functional and structural vascular alterations are also taken into consideration. Edited and written by internationally renowned experts in the field of novel therapeutics for cancer, this book is a valuable source for cancer researchers, medical scientists, clinicians, clinical pharmacologists, and graduate students. Provides readers with a clear overview of the recent findings and references as well as summaries, significant molecular pathways, and conclusions Discusses new ideas proposed and makes suggestions for further investigations that will advance the field Presents introductory and summary information on the contributions of the field, all the findings of the studies discussed, and projects future goals for research
This volume examines in detail the role of chronic inflammatory processes in the development of several types of cancer. Leading experts describe the latest results of molecular and cellular research on infection, cancer-related inflammation and tumorigenesis. Further, the clinical significance of these findings in preventing cancer progression and approaches to treating the diseases are discussed. Individual chapters cover cancer of the lung, colon, breast, brain, head and neck, pancreas, prostate, bladder, kidney, liver, cervix and skin as well as gastric cancer, sarcoma, lymphoma, leukemia and multiple myeloma.
Immune Rebalancing: The Future of Immunosuppression summarizes the most promising perspectives of immunopharmacology, in particular in the area of immunosuppression by considering molecular pathways, personalized medicine, microbiome and nanomedicine. Modulation of immune responses for therapeutic purposes is a particularly relevant area, given the central role of anomalous immunity in diseases. These diseases vary from the most typically immune-related syndromes (autoimmune diseases, allergy and asthma, immunodeficiencies) to those in which altered immunity and inflammation define the pathological outcomes (chronic infections, tumours, chronic inflammatory and degenerative diseases, metabolic disorders, etc. Visits immunosuppression from a modern point of view of signalling mechanisms at the light of the current knowledge of signalling mechanisms and regulatory networks allows the reader to formulate new ideas and concepts on how to use immunosuppression the therapeutic purposes Encourages researchers to engage into exploring the field of pharmacological modulation of immune responses in depth, and with the new knowledge and tools available, designs more effective therapeutic strategies to autoimmune and inflammatory diseases, cancer, degenerative diseases and infections Examines the link between molecular pathways associated to immune-suppression and the new immunopharmacology approaches Provides information on the new strategies for drug development in this field Considers the role of microbes in the development of the mammalian immune system and immune responses, which will widen the reader’s strategy for addressing therapeutic immune modulations
Compiling an up-to-date and detailed survey of the role cytokines play in cell-to-cell communication, development, and differentiation, this comprehensive reference highlights the medical advantages of cytokine inhibition and pursues novel methods of discovery for more potent and specific blocking agents. Investigates the pathogenic role of