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Author: Abdel-Majid Khatib
Publisher: Springer Science & Business Media
ISBN: 1402051328
Category : Medical
Languages : en
Pages : 161
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Book Description
Convertases are widely expressed activating enzymes involved in various physiological and pathological processes. This book provides detailed and updated information on the role of these molecules in cancer. It is the first to summarize current knowledge of the importance of protein precursors maturation by the convertases in tumor progression, angiogenesis and metastasis. Each chapter discusses the importance of the convertases in the activation of various cancer-related molecules including growth factors, adhesion molecules and proteases.
Author: Abdel-Majid Khatib
Publisher: Springer Science & Business Media
ISBN: 1402051328
Category : Medical
Languages : en
Pages : 161
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Book Description
Convertases are widely expressed activating enzymes involved in various physiological and pathological processes. This book provides detailed and updated information on the role of these molecules in cancer. It is the first to summarize current knowledge of the importance of protein precursors maturation by the convertases in tumor progression, angiogenesis and metastasis. Each chapter discusses the importance of the convertases in the activation of various cancer-related molecules including growth factors, adhesion molecules and proteases.
Author: Abdel-Majid Khatib
Publisher: Biota Publishing
ISBN: 1615045376
Category : Science
Languages : en
Pages : 88
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Book Description
Proprotein convertases (PCs) are a family of proteases including PC1, PC2, Furin, PC4, PACE4, PC5, and PC7. These enzymes are involved in the maturation of many precursor proteins involved in the process of tumorigenesis and metastasis. Since their discovery, PCs were suggested as potential targets for anti-cancer therapy, and their activity was found to directly affect tumor cell proliferation, migration invasion, and the malignant phenotypes of tumor cells. Here, we discuss a number of previous and recent findings on the PCs features, their implication in the regulation of multiple cellular functions that impact on the invasive/metastatic potential of cancer cells, and their clinical relevance in cancer patients. Among the substrates of the proprotein convertases, various growth factors, their receptors, adhesion molecules, and proteases were identified. The PCs are inhibited by endogenous and exogenous inhibitors. To date, only pro7B2, a specific chaperone of PC2, and the granine-like precursor of neuroendocrine protein proSAAS, a selective ligand of PC1, have been identified as endogenous inhibitors of the PCs found in the regulated pathway. However, only PCs prosegments, several bioengineered inhibitors, peptides, and non-peptide compounds were found to inhibit the activity of the PCs found in the secretory pathway.
Author: Xiaowei Sun
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
"Cancer is a leading cause of death worldwide and accounts for about one fifth of all death in the Western world. In 2008, nearly 12.7 million new cancer cases and 7.6 million cancer deaths occurred worldwide. The development of cancer is a multistage process, during which cells acquire a series of mutations that eventually lead to unrestrained cell growth, evasion of cell death, angiogenesis, invasion of the surrounding tissue and finally spreading to other parts of the body. The mammalian proprotein convertases (PCs) constitute a family of nine secretory serine proteases that are related to bacterial subtilisin and yeast kexin. They have been associated with cancer since the early 1990s. By processing cancer-associated factors, PCs are believed to play key roles in almost every step of cancer development. Seven of these PCs (PC1, PC2, furin, PC4, PC5/6, PACE4 and PC7) activate, or less frequently inactivate, a wide variety of substrates, including hormones, growth factors, receptors, adhesion molecules, angiogenic factors, metalloproteases. Among these substrates, some of them are key factors controlling cancer progression and metastasis. The last member of this family proprotein convertase subtilisin kexin 9 (PCSK9) only cleaves itself and participates in maintaining the levels of cholesterol, which was shown to have impacts on cancer incidence.In this thesis, I focused on the role of two PCs, PC5/6 and PCSK9, in cancer development. I first showed that PC5/6 is systematically down-regulated in human and mice intestinal tumors. In ApcMin/+ mice which are a colonic cancer model and develop numerous adenocarcinomas along the intestinal tract, the specific knockout of PC5/6 in the intestine and colon leads to higher number of tumors, particularly in duodenum. This suggests that PC5/6 plays a protective role against tumorigenesis in the intestine. Although PC5/6 is protective in intestinal cancer, it has been shown to promote tumor progression in other cancer types e.g., brain and skin. Interestingly, PC5/6 is inhibited by some natural inhibitors, the latent TGFbeta binding proteins 2 and 3 (LTBP-2, -3). These two proteins reduce the enzymatic activity of PC5/6A and reduce the bio-availability of PC5/6A by sequestering the zymogen proPC5/6 in the extracellular matrix. Finally, I demonstrated that the lack of PCSK9 leads to a significantly lower level of liver metastasis of melanoma cells. This cancer protective effect is due to low plasma cholesterol levels as well as high apoptosis in liver stroma and metastasized tumors that are associated with PCSK9 deficiency.In summary, the present cumulative data define some of the in vivo roles of PC5/6 and PCSK9 in cancer and should enhance our appreciation of the physiological impact of PC inhibition." --
Author: Utpal Chandra De
Publisher: Biota Publishing
ISBN: 1615044752
Category : Science
Languages : en
Pages : 78
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Book Description
The Ca+2-dependent mammalian Proprotein Convertase Subtilisin Kexins (PCSKs) or Proprotein/ Prohormone Convertases (PCs) are a family of endoproteases that play critical roles not only in normal development and metabolism but also in various physiological and pathological conditions. These were initiated by the proteolytic processing of large inactive proproteins into their shorter bioactive mature forms by the PCSK enzymes. These events take place in a highly selective, orchestrated, and stepwise manner. Among the various proprotein substrates of PCSK enzymes, particularly important are the precursor growth factors that include proPDGF-A, B, proIGF-1, 2 and proVEGF-C because of their strong implications in neoplasia initiation, progression, and metastasis. As a result of these findings, PCSK enzymes, particularly furin or PCSK3, became a major target for possible interventions of cancer via the use of their selective inhibitors. Significant progress has been accomplished in the development of peptide and protein-based PCSK inhibitors. However, non-peptide PCSK9 inhibitors are more preferable because of their drug-like and other characteristics. So far, a few non-peptide inhibitors of PCSK enzymes of various types of chemical structures have been described in the literature. These include (i) Carbocyclic compounds of diterpene and streptamine class. (ii) Nitrogen (N)-based heterocyclic compounds of various types and chemical structures such as (a) pyrrolidine bis piperazines, (b) Cu/Zn chelating terpyridine derivatives; (iii) Oxygen (O)-based Heterocyclic compounds of varying types of chemical structures such as (a) Flavonoids, (b) Coumarins of simple and dimeric types, (c) Quinonoids, (d) Iridoids; (iv) Aromatic compounds such as (a) Aryl guanidino and amidino derivatives, (b) Naphthyl fluorescein derivative, and (c) Phenyl Arsonic acids; and (v) C2-symmetrical aromatic azo-compounds. When measured against a small peptidyl-MCA fluorogenic substrate, these inhibitors displayed IC50 values ranging from nM to μM. A number of these inhibitors exhibited significant anti-PCSK activity when tested in ex vivo or cell culture conditions. This article provides an overall review of all non-peptide PCSK inhibitors so far reported in the literature along with those we identified recently for the first time and not yet published. The potential implications of these molecules as biochemical, therapeutical, or clinical agents will also be discussed.
Author: Pierre Vereecken
Publisher:
ISBN: 9789535171324
Category :
Languages : en
Pages : 310
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Book Description
Highlights in Skincancer is a companion handbook published expressly for all the practitionners who are interested in skin cancers: medical oncologists and dermatologists but also residents, general practitionners, surgeons, plastic surgeons. The book is designed to teach new aspects of skincancers in the context of practical clinical settings. Each topic is an expert view of a specific skincancer field. Highlights in Skincancer provides information on a wide range of skincancer topics with emphasis on the emergence of new diagnostic approaches, therapeutic perspectives, and a better insight into the biology of the skin tumours. No doubt that the Highlights in Skincancer will be considered as a real tool throughout a medical career.
Author: Ian Tannock
Publisher: McGraw Hill Professional
ISBN: 9780071387743
Category : Medical
Languages : en
Pages : 596
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Book Description
This concise text examines cancer causation and biology as well as the biology underlying cancer treatment. Thoroughly updated and reorganized with five new chapters, the Fourth Edition emphasizes new development in molecular biology, hormone therapy, and the pharmacology of anti-cancer drugs. Features updated coverage of the basic science of radiotherapy and experimental radiation in addition to expansive coverage of new drugs developments.
Author: Aamir Ahmad
Publisher: Springer Nature
ISBN: 3030203018
Category : Medical
Languages : en
Pages : 427
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Book Description
Resistance to therapies, both targeted and systemic, and metastases to distant organs are the underlying causes of breast cancer-associated mortality. The second edition of Breast Cancer Metastasis and Drug Resistance brings together some of the leading experts to comprehensively understand breast cancer: the factors that make it lethal, and current research and clinical progress. This volume covers the following core topics: basic understanding of breast cancer (statistics, epidemiology, racial disparity and heterogeneity), metastasis and drug resistance (bone metastasis, trastuzumab resistance, tamoxifen resistance and novel therapeutic targets, including non-coding RNAs, inflammatory cytokines, cancer stem cells, ubiquitin ligases, tumor microenvironment and signaling pathways such as TRAIL, JAK-STAT and mTOR) and recent developments in the field (epigenetic regulation, microRNAs-mediated regulation, novel therapies and the clinically relevant 3D models). Experts also discuss the advances in laboratory research along with their translational and clinical implications with an overarching goal to improve the diagnosis and prognosis, particularly that of breast cancer patients with advanced disease.
Author: Eva Böttcher-Friebertshäuser
Publisher: Springer
ISBN: 3319754742
Category : Medical
Languages : en
Pages : 337
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Book Description
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.
Author: Wu-Min Deng
Publisher: Springer Nature
ISBN: 3030236293
Category : Medical
Languages : en
Pages : 251
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Book Description
This volume provides a series of review articles that capture the advances in using the fruit fly, Drosophila melanogaster, model system to address a wide range of cancer-related topics. Articles in this book provide case studies that shed light on the intricate cellular and molecular mechanisms underlying tumor formation and progression. Readers will discover the beauty of the fly model’s genetic simplicity and the vast arsenal of powerful genetic tools enabling its efficient and adaptable use. This model organism has provided a unique opportunity to address questions regarding cancer initiation and development that would be extremely challenging in other model systems. This book provides a useful resource for a researcher who wishes to learn about and apply the Drosophila model to tackle fundamental questions in cancer biology, and to find new ways to fight against this devastating disease.
Author:
Publisher: Elsevier
ISBN: 0080490883
Category : Science
Languages : en
Pages : 475
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Book Description
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
