Download or read book Proteases and Their Inhibitors in Cancer Metastasis written by J-M. Foidart and published by Springer. This book was released on 2010-12-09 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: In recent years, serine proteases and matrix metalloproteinases (MMPs) have gained considerable attention in tumor biology. For most of these proteases, their expression is a reliable indication of ongoing tissue remodeling. This book provides a comprehensive evaluation of the mechanisms of action of proteases and their inhibitors in tumor biology. The first part provides the reader with a selective overview of the molecular biology of serine proteases, MMPs and their physiological inhibitors. The most important proteases and their physiological as well as synthetic inhibitors are evaluated in the most relevant models of experimental and human cancer. The clinical aspects are also taken into account. This volume offers an update on this challenging aspect of cancer treatment, its interest bias, and possible clinical implication.
Download or read book Cancer Leading Proteases written by Satya Prakash Gupta and published by Academic Press. This book was released on 2020-02-03 with total page 524 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer-Leading Proteases: Structures, Functions, and Inhibition presents a detailed discussion on the role of proteases as drug targets and how they have been utilized to develop anticancer drugs. Proteases possess outstanding diversity in their functions. Because of their unique properties, proteases are a major focus of attention for the pharmaceutical industry as potential drug targets or as diagnostic and prognostic biomarkers. This book covers the structure and functions of proteases and the chemical and biological rationale of drug design relating to how these proteases can be exploited to find useful chemotherapeutics to fight cancers. In addition, the book encompasses the experimental and theoretical aspects of anticancer drug design based on proteases. It is a useful resource for pharmaceutical scientists, medicinal chemists, biochemists, microbiologists, and cancer researchers working on proteases. Explains the role of proteases in the biology of cancer Discusses how proteases can be used as potential drug targets or as diagnostic and prognostic biomarkers Covers a wide range of cancers and provides detailed discussions on protease examples
Download or read book The Cancer Degradome written by Dylan Edwards and published by Springer Science & Business Media. This book was released on 2008-09-16 with total page 921 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers recent knowledge of the composition of the Degradome, how it can be studied using modern approaches such as transcriptomics and mass spectrometry; and many other relevant subjects, including new approaches to targeting proteolysis for therapy.
Download or read book Cell Surface Proteases written by and published by Elsevier. This book was released on 2003-05-03 with total page 475 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cell Surface Proteases provides a comprehensive overview of these important enzymes that catalyze the hydrolysis of a protein as it degrades to a simpler substance. In the 1990s, an explosion of new discoveries shed light on the role of cell surface proteases and extended it beyond degradation of extracellular matrix components to include its influence on growth factors, cell signaling, and other cellular events. This volume unites the scientific literature from across disciplines and teases out unified themes of interactions between cell surface proteases and interconnecting cell surface-related systems -- including integrins and other adhesion molecules. Scientists and students involved in developmental biology, cell biology and disease processes will find this an indispensable resource. * Provides an overview of the entire field of cell surface proteases in a single volume* Presents major issues and astonishing discoveries at the forefront of modern developmental biology and developmental medicine * A thematic volume in the longest-running forum for contemporary issues in developmental biology with over 30 years of coverage
Download or read book Tumour Cell Surface Proteases and Their Inhibitors written by Mohammad Anees and published by . This book was released on 1995 with total page 167 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Matrix Proteases in Health and Disease written by Niels Behrendt and published by John Wiley & Sons. This book was released on 2012-09-10 with total page 419 pages. Available in PDF, EPUB and Kindle. Book excerpt: Presenting a comprehensive overview of the multifaceted field of proteases in the extracellular matrix environment, this reference focuses on the recently elucidated functions of complex proteolytic systems in physiological and pathological tissue remodeling. The proteases treated include both serine proteases such as plasminogen activators and TTSPs, metalloproteases such as MMPs and ADAMS and cysteine protease cathepsins. The text specifically addresses the role of extracellular proteases in cancer cell invasion, stroke and infectious diseases, describing the basic biochemistry behind these disease states, as well as therapeutic strategies based on protease inhibition. With its trans-disciplinary scope, this reference bridges the gap between fundamental research and biomedical and pharmaceutical application, making this required reading for basic and applied scientists in the molecular life sciences.
Download or read book Medical Aspects of Proteases and Protease Inhibitors written by Nobuhiko Katunuma and published by IOS Press. This book was released on 1997 with total page 224 pages. Available in PDF, EPUB and Kindle. Book excerpt: The work presents articles on proteases and their inhibitors as mediators of biological functions. Topics addressed: cathepsin B and L; MHC and peptide interaction; procathepsin L; cysteine proteinases; selective neuronal cell death; HIV and influenza virus; tumor invasion; gingivitis; bacterial infection. Readers: professionals in the area of molecular medicine, biochemists, molecular biologists, clinical pharmacologists, pharmaceutical companies.
Download or read book Protease Inhibitors as Cancer Chemopreventive Agents written by A.R. Kennedy and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 434 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protease inhibitors (PIs) are widely distributed in plants and animals, and have a variety of functions, which include preventing digestion of seeds by insects and modifying blood clotting in animals. After it was noted that synthetic and natural inhibitors suppress two-stage carcinogenesis and breast cancer, extensive work investigating PIs as chemopreventive agents was started. PIs are unique in that they interfere with cancer development in a variety of ways, including suppression of oxygen radicals, oncogenes, and metastases. Epidemiologic evidence supports their prevention of major human cancers in populations that consume foods containing them. Their supervised use in humans is on the threshold of development. The epidemiologic discovery of the importance of lentils and other seeds rich in PIs in preventing many human cancers allowed us to look at the action of PIs as chemopreventive agents, as reviewed in Chapter I (Fontham and Correa). Chapter 2 (Kennedy) discusses the role of natural PIs (e. g. , the Bowman-Birk inhibitor) as anticarcinogens and the possible limitations of their use. In Chapter 3 (Kennedy), the transformation of C3HI lOTlh cells caused by carcinogens and promoters is shown to be suppressed by PIs. Bowman (Chapter 4) relates the discovery of inhibitors in soybeans that are distinct from the Kunitz inhibitor, and the occurrence of a similar inhibitor in peanuts and other legumes. Chapter 5 (Birk) is an overview of PIs of plant origin and their role in human nutrition.
Download or read book Cell Surface Regulation of Matrix Metalloproteinases in Breast Cancer Cells written by and published by . This book was released on 2003 with total page 110 pages. Available in PDF, EPUB and Kindle. Book excerpt: Metastasis is the major cause of death in breast cancer patients and is partly caused by the action of proteolytic enzymes that degrade extracellular matrix (ECM). We have focused on the gelatinases, MMP-2, and MMP-9, two ECM-degrading enzymes that are members of the matrix metalloproteinase (MMP) family of proteases. The gelatinases are associated with the surface of breast cancer cells. MMP-2 surface binding plays a role in activation by MT1-MMP, a membrane-bound MMP that is also expressed in breast cancer cells. MMP-2 activation is mediated by the action of TIMP-2, a metalloproteinase inhibitor. We characterized in detail the process of pro-MMP-2 activation by MT1-MMP and demonstrated the role of TIMP-2 in this process. The regulation of MT1-MMP on the cell surface was also investigated. These studies demonstrated that MT1-MMP undergoes autocatalytic processing and ectodomain shedding, which serve to control the level of MT1-MMP on the cell surface and produce active enzyme at both the cell membrane and in the extracellular space. MT1- MMP initiates a cascade of zymogen activation on the cell surface that leads to the generation of active MMP-2 and active MMP-9. This process is regulated by TIMP-2. A novel mechanism-based inhibitor for the gelatinases that binds with high affinity and irreversible has been characterized. Together, these studies have defined some key aspects that regulate the function of the MT1-MMP/gelatinase axis on the surface of breast cancer cells and develop new approaches to counteract their action in tumor tissues.
Download or read book Development of Phosphoramidate Inhibitors for Cell Surface Proteases in Metastatic Cancers written by Desiree Ellene Mendes and published by . This book was released on 2016 with total page 142 pages. Available in PDF, EPUB and Kindle. Book excerpt: The development of highly tuned diagnostic agents are critical for the early detection of cancer and are commonly designed to bind cell surface receptors. A small library of first-generation phosphoramidate inhibitors leading to sub-micromolar potency as determined by a FRET-based spectrophotometric assay were generated as peptide mimics with a scaffold designed to interact with the S1, S1` register of the catalytic domain of the cell surface receptor matrix metalloproteinase (MMP-14). Candidate residues were selected for the scaffold using in silico modeling, and synthesized using organophosphate and peptide coupling methodologies. A phosphoramidate inhibitor and fluorescent conjugate were shown to specifically target prostate specific membrane antigen (PSMA) in human cancer cell lines was applied to a canine model of which the expression and enzymatic activity of PSMA were previously unknown. The expression of PSMA was determined by RT-PCR and western blot and found to be in lower abundance when compared to human prostate cancer PSMA expression. The kinetics of PSMA were established and inhibitory potency was determined by an end-point HPLC analysis, and was similar to that of human PSMA enzymatic activity. In addition, a fluorescent-conjugate was successfully used to label canine cancer cells in blood as detected using flow cytometry. Previous studies revealed that both PSMA and androgen receptor (AR) decreased following an extended period of androgen deprivation. When the biomarker expression of c-Met and calpain 2 are upregulated, it indicated a switch to a more aggressive prostate cancer phenotype. The expression of these biomarkers in prostate cancer cell lines subjected to prolonged androgen deprivation in an established in vitro model were investigated. After 10 passages of prolonged androgen deprivation, both c-Met and calpain 2 were found to be upregulated with the concomitant decrease in expression of PSMA and AR. In addition to switching signaling pathways, prostate cancer cells secrete exosomes as long-range cell-to-cell communication vehicles. The exosomes were found to be highly enriched with functionally active PSMA. Insights into inhibitor binding, signaling pathway alterations, and biomarker expression in extracellular vesicles could enable new trajectories for treatment and further the advancement toward powerful development of personalized cancer therapy.
Download or read book Chemistry and Biology of Serpins written by Frank C. Church and published by Springer. This book was released on 2011-09-26 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proceedings of an International Symposium held in Chapel Hill, North Carolina, April 13-16, 1996
Download or read book Extracellular Matrix Degradation written by William C. Parks and published by Springer Science & Business Media. This book was released on 2011-04-07 with total page 262 pages. Available in PDF, EPUB and Kindle. Book excerpt: Regulated turnover of extracellular matrix (ECM) is an important component of tissue homeostasis. In recent years, the enzymes that participate in, and control ECM turnover have been the focus of research that touches on development, tissue remodeling, inflammation and disease. This volume in the Biology of Extracellular Matrix series provides a review of the known classes of proteases that degrade ECM both outside and inside the cell. The specific EMC proteases that are discussed include cathepsins, bacterial collagenases, matrix metalloproteinases, meprins, serine proteases, and elastases. The volume also discusses the domains responsible for specific biochemical characteristics of the proteases and the physical interactions that occur when the protease interacts with substrate. The topics covered in this volume provide an important context for understanding the role that matrix-degrading proteases play in normal tissue remodeling and in diseases such as cancer and lung disease.
Download or read book Extracellular Targeting of Cell Signaling in Cancer written by James W. Janetka and published by John Wiley & Sons. This book was released on 2018-07-23 with total page 482 pages. Available in PDF, EPUB and Kindle. Book excerpt: International experts present innovative therapeutic strategies to treat cancer patients and prevent disease progression Extracellular Targeting of Cell Signaling in Cancer highlights innovative therapeutic strategies to treat cancer metastasis and prevent tumor progression. Currently, there are no drugs available to treat or prevent metastatic cancer other than non-selective, toxic chemotherapy. With contributions from an international panel of experts in the field, the book integrates diverse aspects of biochemistry, molecular biology, protein engineering, proteomics, cell biology, pharmacology, biophysics, structural biology, medicinal chemistry and drug development. A large class of proteins called kinases are enzymes required by cancer cells to grow, proliferate, and survive apoptosis (death) by the immune system. Two important kinases are MET and RON which are receptor tyrosine kinases (RTKs) that initiate cell signaling pathways outside the cell surface in response to extracellular ligands (growth factors.) Both kinases are oncogenes which are required by cancer cells to migrate away from the primary tumor, invade surrounding tissue and metastasize. MET and RON reside on both cancer cells and the support cells surrounding the tumor, called the microenvironment. MET and RON are activated by their particular ligands, the growth factors HGF and MSP, respectively. Blocking MET and RON kinase activation and downstream signaling is a promising therapeutic strategy for preventing tumor progression and metastasis. Written for cancer physicians and biologists as well as drug discovery and development teams in both industry and academia, this is the first book of its kind which explores novel approaches to inhibit MET and RON kinases other than traditional small molecule kinase inhibitors. These new strategies target key tumorigenic processes on the outside of the cell, such as growth factor activation by proteases. These unique strategies have promising potential as an improved alternative to kinase inhibitors, chemotherapy, or radiation treatment.
Download or read book Activation of Viruses by Host Proteases written by Eva Böttcher-Friebertshäuser and published by Springer. This book was released on 2018-05-22 with total page 337 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book will give an overview on viruses undergoing proteolytic activation through host proteases. The chapters will be organized in three themed parts, the first part describing respective viruses and their characteristics in detail. In the second part the molecular and cellular biology of the proteases involved as well as their physiological functions will be further explored. The third part will contain a chapter on protease inhibitors that are promising tools for antiviral therapy. This book will engage scholars in virology and medical microbiology as well as researchers with an interest in enzymology and protein structure and function relationship.
Download or read book Matrix Metalloproteinase Inhibitors in Cancer Therapy written by Neil J. Clendeninn and published by Springer Science & Business Media. This book was released on 2000-09-17 with total page 371 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Proteases in Physiology and Pathology written by Sajal Chakraborti and published by Springer. This book was released on 2017-09-14 with total page 619 pages. Available in PDF, EPUB and Kindle. Book excerpt: Using a multidisciplinary approach, this book describes the biochemical mechanisms associated with dysregulation of proteases and the resulting pathophysiological consequences. It highlights the role and regulation of different types of proteases as well as their synthetic and endogenous inhibitors. The role of proteases was initially thought to be limited to general metabolic digestion. However, we now know that the role of protein breakdown is much more complex, and proteases have multiple functions: they are coupled to turnover and can affect protein composition, function and synthesis. In addition to eliminating abnormal proteins, breakdown has many modulatory functions, including activating and inactivating enzymes, modulating membrane function, altering receptor channel properties, affecting transcription and cell cycles and forming active peptides. The ubiquity of proteases in nature makes them an important target for drug development. This in-depth, comprehensive is a valuable resource for researchers involved in identifying new targets for drug development. With its multidisciplinary scope, it bridges the gap between fundamental and translational research in the biomedical and pharmaceutical industries, making it thought-provoking reading for scientists in the field.
Download or read book Proteases and Their Inhibitors in Cancer Metastasis written by J-M. Foidart and published by Springer Science & Business Media. This book was released on 2002 with total page 259 pages. Available in PDF, EPUB and Kindle. Book excerpt: In recent years, serine proteases and matrix metalloproteinases (MMPs) have gained considerable attention in tumor biology. For most of these proteases, their expression is a reliable indication of ongoing tissue remodeling. This book provides a comprehensive evaluation of the mechanisms of action of proteases and their inhibitors in tumor biology. The first part provides the reader with a selective overview of the molecular biology of serine proteases, MMPs and their physiological inhibitors. The most important proteases and their physiological as well as synthetic inhibitors are evaluated in the most relevant models of experimental and human cancer. The clinical aspects are also taken into account. This volume offers an update on this challenging aspect of cancer treatment, its interest bias, and possible clinical implication.
