Research in the matrix metalloproteinase field began with the demonstration by Gross and Lapière, in 1962, that resorbing tadpole tail expressed an enzyme that could degrade collagen gels. These humble beginnings have led us to the elucidation of around twenty distinct vertebrate MMPs, along with a variety of homologs from such diverse organisms as sea urchin, plants, nematode worm, and bacteria. This, coupled with four known specific inhibitors of MMPs, the TIMPs, gives a complex picture. Part I of Matrix Metalloproteinase Protocols provides the reader with a selective overview of the MMP arena, and a chance to come to grips with where the field has been, where it is, and where it is going. I hope that this complements all of the methodology that comes later. Part II presents the reader with a diverse set of methods for the expression and purification of MMPs and TIMPs, bringing together the long and often hard-earned experience of a number of researchers. Part III allows the reader to detect MMPs and TIMPs at both the protein and mRNA level, whereas Part IV gives the ability to assay MMP and TIMP activities in a wide variety of circumstances.

Cutting-edge investigators review the current status of the entire field, from the biology of MMPs through the current clinical studies. The authors include many leading scientists from pharmaceutical companies who present all the latest concepts and results on the preferred design strategies for MMP inhibitors, their molecular mechanisms, and their substrates. In addition, they fully describe their personal research on specific MMP inhibitors, detailing vanguard design strategies, their in vitro activity, the outcome of animal model studies and, where available, their toxicology, safety, efficacy in human clinical trials. Comprehensive and state-of-the-art, Matrix Metalloproteinase Inhibitors in Cancer Therapy offers basic and clinical investigators alike a richly informative summary of all the latest research on these powerful new drugs, and their high promise as emerging cancer therapeutics.

This detailed volume examines the latest techniques and protocols associated with zymography, the practice of detecting enzyme activity on electrophoretic gels. Sections cover subjects such as endopeptidase zymography, reverse zymography & in situ zymography, 2D zymography, as well as a variety of special cases. Written in the highly respected Methods in Molecular Biology series format, chapters include brief introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and practical, Zymography: Methods and Protocols serves as an ideal aid for a broad array of researchers from the fields of biological and medicinal science, as well as scientists working in clinical and diagnostic medicine, medical genetics, agricultural entomology, genetic monitoring of environmental pollution, and forensic science.

This volume explores the role of proteases in various catalytic classes and cellular processes associated with cancer. The chapters in this book cover topics such as encoding proteolytic enzymes, cleavage sites of proteases, functional catalytic domains of MMPs, zymography, angiogenesis and lymphangiogenesis, genetic and epigenetic alterations of metallopeptidases, and methods to target metalloproteinases. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and cutting edge, Proteases and Cancer: Methods and Protocols is a valuable resource for clinical researchers across numerous fields such as molecular and cellular biology, oncology, biochemistry, and chemistry. This book is also useful for PhD students in the various disciples of health sciences.

Matrix Metalloproteinases and Tissue Remodeling in Health and Disease: Target Tissues and Therapy, Volume, Volume 148, the latest volume in the Progress in Molecular Biology and Translational Science series covers a variety of timely topics, with chapters focusing on The Role of Matrix Metalloproteinases in Development, Repair, and Destruction of the Lungs, Matrix Metalloproteinases in Kidney Disease: Role in Pathogenesis and Potential as a Therapeutic Target, Regulation of Matrix Metalloproteinase in the Pathogenesis of Diabetic Retinopathy, Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia, and Matrix Metalloproteinases, Neural Extracellular Matrix, and Central Nervous System Pathology. This volume is the second part of a thematic on matrix metalloproteinases and tissue remodeling in health and disease. It focuses on the role of MMPs in other systems, target tissues, and pathological disorders and the potential benefits of MMP inhibitors in various disorders. Serves as the second part of a thematic on matrix metalloproteinases and tissue remodeling in health and disease Focuses on cardiovascular remodeling Contains contributions from leading authorities on the topics Publishes cutting-edge reviews in molecular biology

Inflammation has been described as the basis of many pathologies of human disease. When one considers the updated signs of inflammation, they would be vasodilation, cell migration, and, in the case of chronic inflam- tion, cell proliferation, often with an underlying autoimmune basis. Gen- ally, inflammation may be divided into acute, chronic, and autoimmune, - though the editors believe that most, if not all, chronic states are often the result of an autoimmune response to an endogenous antigen. Thus, a proper understanding of the inflammatory basis may provide clues to new therap- tic targets not only in classical inflammatory diseases, but atherosclerosis, cancer, and ischemic heart disease as well. The lack of advances in classical inflammatory diseases, such as rh- matoid arthritis, may in part arise from a failure to classify the disease into different forms. That different forms exist is exemplified in patients with d- fering responses to existing antiinflammatory drugs, ranging from nonresponders to very positive responders for a particular nonsteroidal an- inflammatory drug (NSAID). Though researchers have progressively unr- eled the mechanisms, the story is far from complete. It should also be noted that the inflammatory response is part of the innate immune response, or to use John Hunter’s words in 1795, “inflammation is a salutary response.” That may be applied in particular to the defensive response to invading micro- ganisms.

In Volume I, Analysis of Cells and Tissues, we presented a range of protocols aimed at mapping and analyzing the expression of various molecules of pot- tial interest in metastasis research and for examining their production at the genetic level. In this second volume of metastasis research protocols, we move to the level of living cells and tissues and present methodologies applicable to examining metastatic behavior in vitro and in whole animal models. The methods described in the first section of this volume concentrate on the separation of cell lines with high and low metastatic potential, including the genetic modification of cell lines. The assay systems to test defined aspects of the metastatic cascade are then described in Part II and include cell migration assays, assays for matrix degrading enzymes, basement membrane degrading assays, adhesion assays, and assays of angiogenesis. The role of the specific elements of the metastatic cascade assayed in each of these systems in turn must of course be put into perspective relative to their roles in entire living organisms.