Senescence Associated Secretory Phenotypes Reveal Cell Nonautonomous Functions Of Oncogenic Ras And The P53 Tumor Suppressor
DOWNLOAD
Download Senescence Associated Secretory Phenotypes Reveal Cell Nonautonomous Functions Of Oncogenic Ras And The P53 Tumor Suppressor PDF/ePub or read online books in Mobi eBooks. Click Download or Read Online button to get Senescence Associated Secretory Phenotypes Reveal Cell Nonautonomous Functions Of Oncogenic Ras And The P53 Tumor Suppressor book now. This website allows unlimited access to, at the time of writing, more than 1.5 million titles, including hundreds of thousands of titles in various foreign languages. If the content not found or just blank you must refresh this page
Senescence Associated Secretory Phenotypes Reveal Cell Nonautonomous Functions Of Oncogenic Ras And The P53 Tumor Suppressor
DOWNLOAD
Author :
language : en
Publisher:
Release Date : 2008
Senescence Associated Secretory Phenotypes Reveal Cell Nonautonomous Functions Of Oncogenic Ras And The P53 Tumor Suppressor written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008 with categories.
Cellular senescence suppresses cancer by arresting cell proliferation, essentially permanently, in response to oncogenic stimuli, including genotoxic stress. We modified the use of antibody arrays to provide a quantitative assessment of factors secreted by senescent cells. We show that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy. This senescence-associated secretory phenotype (SASP) developed slowly over several days and only after DNA damage of sufficient magnitude to induce senescence. Remarkably similar SASPs developed in normal fibroblasts, normal epithelial cells, and epithelial tumor cells after genotoxic stress in culture, and in epithelial tumor cells in vivo after treatment of prostate cancer patients with DNA-damaging chemotherapy. In cultured premalignant epithelial cells, SASPs induced an epithelial-mesenchyme transition and invasiveness, hallmarks of malignancy, by a paracrine mechanism that depended largely on the SASP factors interleukin (IL)-6 and IL-8. Strikingly, two manipulations markedly amplified, and accelerated development of, the SASPs: oncogenic RAS expression, which causes genotoxic stress and senescence in normal cells, and functional loss of the p53 tumor suppressor protein. Both loss of p53 and gain of oncogenic RAS also exacerbated the promalignant paracrine activities of the SASPs. Our findings define a central feature of genotoxic stress-induced senescence. Moreover, they suggest a cell-nonautonomous mechanism by which p53 can restrain, and oncogenic RAS can promote, the development of age-related cancer by altering the tissue microenvironment.
Signaling Pathways That Regulate Cellular Senescence
DOWNLOAD
Author : Adam Mark Freund
language : en
Publisher:
Release Date : 2010
Signaling Pathways That Regulate Cellular Senescence written by Adam Mark Freund and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with categories.
Chronic inflammation is associated with aging and plays a causative role in several age-related diseases such as cancer, atherosclerosis, and osteoarthritis. Studies have shown that cellular senescence, a tumor suppressive stress response that is also associated with aging, entails a striking increase in the secretion of pro-inflammatory proteins, termed the senescence-associated secretory phenotype (SASP), which might be an important contributor to chronic inflammation. Little is known about pathways that regulate the SASP, or how those pathways overlap with the pathways that regulate the senescence growth arrest, such as p53 and p16INK4A. We previously showed that DNA damage response (DDR) signaling is essential but not sufficient to establish and maintain the SASP. Additionally, p53, while required for senescence growth arrest, is not required for the SASP and in fact restrains the phenotype. In this dissertation, I delineate a crucial pathway for regulating the SASP and its relationship to the classic DDR and p53. I show, in normal human fibroblasts, that senescence-inducing stimuli such as ionizing radiation or oncogenic RAS activate p38MAPK with kinetics that parallel the development of the SASP. p38MAPK was required for the majority of SASP expression, and constitutive activation of p38MAPK was sufficient to induce a robust SASP. Moreover, p53 restrained p38MAPK activation such that p38MAPK was more active in p53-deficient cells, and the amplified SASP caused by p53 deficiency was p38MAPK dependent. Further, p38MAPK activation was independent of the DDR and constitutive p38MAPK activation induced a SASP without inducing DDR signaling. Mechanistically, p38MAPK induced the SASP at the mRNA level by increasing NF-[kappa]B transcriptional activity. These findings assign p38MAPK a novel role in SASP regulation - one that is independent of previously described pathways. I also examined how the p38MAPK/NF-[kappa]B pathway affected the senescence growth arrest. p38MAPK was required for oncogene-induced growth arrest, however it was not required for DNA damage-induced growth arrest, and NF-[kappa]B was not required for growth arrest in either context or for p38MAPK-induced senescence. Thus, p38MAPK regulates the SASP but not growth arrest via NF-[kappa]B, demonstrating a bifurcation in the growth arrest/SASP pathways downstream of p38MAPK. These findings demonstrate how the SASP and growth arrest can be independently regulated, suggesting possibilities for mitigating the deleterious effects of the SASP without adversely affecting the tumor suppressive growth arrest. Additionally, these data have implications for our understanding of growth arrest regulation in oncogenic backgrounds. Lastly, I identified lamin B1 loss as a novel biomarker of senescence that is independent of other senescence regulatory pathways and may serve as a useful tool for identifying senescent cells in multiple contexts.
Host Response To Biomaterials
DOWNLOAD
Author : Stephen F. Badylak
language : en
Publisher: Academic Press
Release Date : 2015-05-08
Host Response To Biomaterials written by Stephen F. Badylak and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-05-08 with Medical categories.
Host Response to Biomaterials: The Impact of Host Response on Biomaterial Selection explains the various categories of biomaterials and their significance for clinical applications, focusing on the host response to each biomaterial. It is one of the first books to connect immunology and biomaterials with regard to host response. The text also explores the role of the immune system in host response, and covers the regulatory environment for biomaterials, along with the benefits of synthetic versus natural biomaterials, and the transition from simple to complex biomaterial solutions. Fields covered include, but are not limited to, orthopaedic surgery, dentistry, general surgery, neurosurgery, urology, and regenerative medicine. Explains the various categories of biomaterials and their significance for clinical applications Contains a range of extensive coverage, including, but not limited to, orthopedic, surgery, dental, general surgery, neurosurgery, lower urinary tract, and regenerative medicine Includes regulations regarding combination devices
Cellular Senescence In Disease
DOWNLOAD
Author : Manuel Serrano
language : en
Publisher: Academic Press
Release Date : 2021-11-27
Cellular Senescence In Disease written by Manuel Serrano and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021-11-27 with Science categories.
Winner of the 2023 PROSE award in Biomedicine and Neuroscience! Research in the field of senescence has boomed recently due to the gradual realization that senescent cells are associated with a significant number of diseases. The genetic or pharmacological elimination of senescent cells can cause widespread benefits and improves outcomes for most of those diseases. Cellular Senescence in Diseases presents an updated review of the role of cellular senescence in multiple pathologies. Focus is given to those diseases where the implication of senescence has been more extensively documented, such as (cancer, lung and liver diseases, diabetes, Neurodegenerative diseases and others). The Editors recruited a group of worldwide experts in each individual pathology to review the role of cellular senescence in each one of them, aiming at identifying potential therapeutic pathways. The first two chapters provide an overview of the cellular senescence principles. Next, the chapters are divided into specific diseases. Cancer, including premalignant lesions (OIS), Advanced disease (TIS), and Metastasis are covered. The following condition covered is Lund diseases, including IPF, COPD, and Pulmonary Hypertension. Next Liver Diseases are covered, including Fibrosis and Cirrhosis, and Fatty liver disease. Next there is coverage for Kidney implications, including fibrosis and transplantation. Vascular diseases are covered next including infarction and hear fibrosis, and atherosclerosis. Both diabetes types 1 and 2 are covered next. Following chapters cover Obesity, Sarcopenia, and Bone and Cartilage disorders, respectively. Neurodegenerative diseases are covered next, focusing on Alzheimer and Parkinson. The next chapter discusses accumulation of senescent cell in tissues during aging. The two final chapters cover current developments and conclusions. Cellular Senescence in Diseases is designed for researchers and clinicians with a focus on the cellular mechanisms of diseases. All chapters cover current experimental therapeutic approaches to eliminate or cancel the pathological effects of senescent cells. Pharmaceutical scientists may also benefit from the contents of the book in the exploration of novel therapeutic opportunities. 2023 PROSE Awards - Winner: Category: Biomedicine and Neuroscience: Association of American Publishers Provides a thorough introduction to Cellular Senescence Covers all major pathologies for which cellular senescence has shown evidence of involvement Focuses on possible therapeutic pathways Edited and authored by worldwide experts
Anti Aging Drug Discovery On The Basis Of Hallmarks Of Aging
DOWNLOAD
Author : Sandeep Kumar Singh
language : en
Publisher: Academic Press
Release Date : 2022-07-19
Anti Aging Drug Discovery On The Basis Of Hallmarks Of Aging written by Sandeep Kumar Singh and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-07-19 with Medical categories.
Anti-Aging Drug Discovery on the Basis of Hallmarks of Aging is a comprehensive and timely book on all aspects of anti-aging strategies. The book provides comprehensive, foundational knowledge on the mechanisms of aging and current anti-aging strategies and approaches developed. Aging research has experienced an unprecedented advance over recent years with the discovery that the rate of aging is determined, at least to some extent, mainly by our genetics and modulated by environmental factors. The hallmarks of aging describe the molecular and cellular processes that govern biological aging and their variation in individuals. Covers different aspects of anti-aging research, from foundational knowledge to future perspectives Provides understanding on the different hallmarks of aging and how they can be applied in the development of anti-aging drugs Discusses various anti-aging strategies, including telomerase reactivation, clearance of senescent cells, stem cell-based therapy, and others
Cellular Senescence And Aging
DOWNLOAD
Author :
language : en
Publisher: Elsevier
Release Date : 2024-01-30
Cellular Senescence And Aging written by and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2024-01-30 with Science categories.
Cellular Senescence and Aging, Volume 181 in the Methods in Cell Biology series, highlights new advances in the field, with this new volume presenting interesting chapters on topics such as assessing polyglutamine tract aggregation in the nematode Caenorhabditis elegans, Generation of glial cell-derived neurotrophic factor (gdnf) morphants in zebrafish larvae by cerebroventricular microinjection of vivo morpholino, Methods for detection of mitochondrial reactive oxygen species in senescent cells, Assessment of cell cycle progression and mitotic slippage by videomicroscopy, The original colorimetric method to detect cellular senescence, and more. Additional sections cover Assessing microbiota composition in the context of aging, Assessing chronological aging in Saccharomyces cerevisiae, Image processing and supervised machine learning for retinal microglia characterization in senescence, Measuring telomerase activity using TRAP assays, High throughput assessment of cellular senescence, Detection of radiation-induced senescence by the Debacq-Chainiaux protocol: Improvements and upgrade in the detection of positive events, Dynamic and scalable assessment of the senescence-associated secretory phenotype (SASP), Flow cytometry-assisted quantification of cell cycle arrest in cancer cells treated with CDK4/6 inhibitors, and more. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Methods in Cell Biology series Updated release includes the latest information on Cellular Senescence and Aging
Hsf1 And Molecular Chaperones In Biology And Cancer
DOWNLOAD
Author : Marc Laurence Mendillo
language : en
Publisher: Springer Nature
Release Date : 2020-04-15
Hsf1 And Molecular Chaperones In Biology And Cancer written by Marc Laurence Mendillo and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-04-15 with Medical categories.
Protein homeostasis, or “Proteostasis”, lies at the heart of human health and disease. From the folding of single polypeptide chains into functional proteins, to the regulation of intracellular signaling pathways, to the secreted signals that coordinate cells in tissues and throughout the body, the proteostasis network operates to support cell health and physiological fitness. However, cancer cells also hijack the proteostasis network and many of these same processes to sustain the growth and spread of tumors. The chapters in this book are written by world experts in the many facets of the proteostasis network. They describe cutting-edge insights into the structure and function of the major chaperone and degradation systems in healthy cells and how these systems are co-opted in cancer cells and the cells of the tumor microenvironment. The chapters also cover therapeutic interventions such as the FDA-approved proteasome inhibitors Velcade and Krypolis as well as other therapies currently under clinical investigation to disarm the ability of the proteostasis network to support malignancy. This compendium is the first of its kind and aims to serve as a reference manual for active investigators and a primer for newcomers to the field. This book is dedicated to the memory of Susan Lindquist, a pioneer of the proteostasis field and a champion of the power of basic scientific inquiry to unlock the mechanisms of human disease. The chapter “Reflections and Outlook on Targeting HSP90, HSP70 and HSF1 in Cancer: A Personal Perspective” is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Immunosenescence And Clinical Consequences
DOWNLOAD
Author : Valquiria Bueno
language : en
Publisher: Frontiers Media SA
Release Date : 2021-08-10
Immunosenescence And Clinical Consequences written by Valquiria Bueno and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021-08-10 with Medical categories.
The New Dynamics Of Ageing Volume 2
DOWNLOAD
Author : Alan Walker
language : en
Publisher: Policy Press
Release Date : 2018-07-25
The New Dynamics Of Ageing Volume 2 written by Alan Walker and has been published by Policy Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-07-25 with Social Science categories.
This volume and its companion, The new dynamics of ageing volume 1, provide comprehensive multi-disciplinary overviews of the very latest research on ageing. Together they report the outcomes of the most concerted investigation ever undertaken into both the influence shaping the changing nature of ageing and its consequences for individuals and society. This book concentrates on four major themes: autonomy and independence in later life, biology and ageing, food and nutrition and representation of old age. Each chapter provides a state of the art topic summary as well as reporting the essential research findings from New Dynamics of Ageing research projects. There is a strong emphasis on the practical implications of ageing and how evidence-based policies, practices and new products can produce individual and societal benefits.
Interaction Of Immune And Cancer Cells
DOWNLOAD
Author : Magdalena Klink
language : en
Publisher: Springer Science & Business Media
Release Date : 2013-11-26
Interaction Of Immune And Cancer Cells written by Magdalena Klink and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-11-26 with Medical categories.
The tumor environment is a dynamic network that includes cancer cells, immune cells, fibroblasts, endothelial cells, extracellular matrix, cytokines and receptors. The aim of this book is to summarize the role of these components, especially immune cells, in tumor suppression and/or progression and describe in detail why tumor cells can survive and spread in spite of the antitumor response of immune cells. Since immunotherapy is an attractive approach to cancer therapy, this book also provides information on the two main strategies: monoclonal antibodies and adaptive T cell immunotherapy, with a focus on recent human clinical trials. The book provides a state-of-the-art, comprehensive overview of immune cells in cancer and is an indispensable resource for scientists and medical doctors working and/or lecturing in the field of cancer research and immunology.
