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Author: Chang-Shi Chen
Publisher:
ISBN:
Category : Antineoplastic agents
Languages : en
Pages :
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Book Description
Abstract: Histone deacetylase (HDAC) is recognized as one of the promising targets for cancer therapy as aberrant transcriptional regulation of the epigenetic system has been linked to tumorigenesis. To date, many HDAC inhibitors have entered clinical trials in light of their high potency in inhibiting tumor cell growth without incurring significant toxicity. Although the effects of HDAC inhibitors on chromatin remodeling and transcriptional regulation are well understood, an increasing body of evidence suggests that modulation of gene expression might not be exclusively responsible for the antineoplastic effects of these agents. In the first part of this study, we demonstrate a novel histone acetylation-independent mechanism by which HDAC inhibitor induces Akt dephosphorylation in U87MG glioblastoma cells by disrupting HDAC-protein phosphatase 1 (PP1) complexes. This selective histone acetylation-independent action of HDAC inhibitors on HDAC-PP1 complexes also represents the first example of modulating specific PP1 interactions by small-molecule agents. The results of the second part of this study present the efficacy of (S)-HDAC-42, a novel HDAC inhibitor synthesized in our laboratory, in prostate cancer cells. We demonstrate that the antitumor effects of (S)-HDAC-42 are attributed to both histone acetylation-dependent and -independent mechanisms by interfering with the activation or expression status of a number of signaling targets. Together, these mechanisms provide a molecular basis to account for the efficacy of (S)-HDAC-42 in suppressing established prostate xenograft tumor growth. The third part of this study reports another transcriptional regulation-independent anticancer effect of HDAC inhibitor; the inhibition of DNA damage repair. We show that pretreatment of the Bax-deficient DU-145 cells with HDAC inhibitors increased Ku70 acetylation, thereby reducing Ku70's DNA end-binding affinity and diminishing the cellular capability to repair DNA damage. The ability of HDAC inhibitors to modify DNA damage repair underlies the viability of their combination with DNA damaging agents as a therapeutic strategy for prostate cancer. This dissertation research characterizes two novel histone acetylation-/transcriptional regulation-independent anticancer effects of HDAC inhibitors. Moreover, we also show that these histone acetylation-dependent and -independent mechanisms underscore the pleiotropic antineoplastic effects of HDAC inhibitors at both epigenetic and cellular levels.
Author: Chang-Shi Chen
Publisher:
ISBN:
Category : Antineoplastic agents
Languages : en
Pages :
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Book Description
Abstract: Histone deacetylase (HDAC) is recognized as one of the promising targets for cancer therapy as aberrant transcriptional regulation of the epigenetic system has been linked to tumorigenesis. To date, many HDAC inhibitors have entered clinical trials in light of their high potency in inhibiting tumor cell growth without incurring significant toxicity. Although the effects of HDAC inhibitors on chromatin remodeling and transcriptional regulation are well understood, an increasing body of evidence suggests that modulation of gene expression might not be exclusively responsible for the antineoplastic effects of these agents. In the first part of this study, we demonstrate a novel histone acetylation-independent mechanism by which HDAC inhibitor induces Akt dephosphorylation in U87MG glioblastoma cells by disrupting HDAC-protein phosphatase 1 (PP1) complexes. This selective histone acetylation-independent action of HDAC inhibitors on HDAC-PP1 complexes also represents the first example of modulating specific PP1 interactions by small-molecule agents. The results of the second part of this study present the efficacy of (S)-HDAC-42, a novel HDAC inhibitor synthesized in our laboratory, in prostate cancer cells. We demonstrate that the antitumor effects of (S)-HDAC-42 are attributed to both histone acetylation-dependent and -independent mechanisms by interfering with the activation or expression status of a number of signaling targets. Together, these mechanisms provide a molecular basis to account for the efficacy of (S)-HDAC-42 in suppressing established prostate xenograft tumor growth. The third part of this study reports another transcriptional regulation-independent anticancer effect of HDAC inhibitor; the inhibition of DNA damage repair. We show that pretreatment of the Bax-deficient DU-145 cells with HDAC inhibitors increased Ku70 acetylation, thereby reducing Ku70's DNA end-binding affinity and diminishing the cellular capability to repair DNA damage. The ability of HDAC inhibitors to modify DNA damage repair underlies the viability of their combination with DNA damaging agents as a therapeutic strategy for prostate cancer. This dissertation research characterizes two novel histone acetylation-/transcriptional regulation-independent anticancer effects of HDAC inhibitors. Moreover, we also show that these histone acetylation-dependent and -independent mechanisms underscore the pleiotropic antineoplastic effects of HDAC inhibitors at both epigenetic and cellular levels.
Author: Brian G. Henning
Publisher: Lexington Books
ISBN: 0739174371
Category : Philosophy
Languages : en
Pages : 488
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Book Description
It has been said that new discoveries and developments in the human, social, and natural sciences hang “in the air” (Bowler, 1983; 2008) prior to their consummation. While neo-Darwinist biology has been powerfully served by its mechanistic metaphysic and a reductionist methodology in which living organisms are considered machines, many of the chapters in this volume place this paradigm into question. Pairing scientists and philosophers together, this volume explores what might be termed “the New Frontiers” of biology, namely contemporary areas of research that appear to call an updating, a supplementation, or a relaxation of some of the main tenets of the Modern Synthesis. Such areas of investigation include: Emergence Theory, Systems Biology, Biosemiotics, Homeostasis, Symbiogenesis, Niche Construction, the Theory of Organic Selection (also known as “the Baldwin Effect”), Self-Organization and Teleodynamics, as well as Epigenetics. Most of the chapters in this book offer critical reflections on the neo-Darwinist outlook and work to promote a novel synthesis that is open to a greater degree of inclusivity as well as to a more holistic orientation in the biological sciences.
Author: Shelley L. Berger
Publisher: Springer Science & Business Media
ISBN: 354037633X
Category : Science
Languages : en
Pages : 223
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Book Description
Methylation of DNA at cytosine residues as well as post-translational modifications of histones, including phosphorylation, acetylation, methylation and ubiquitylation, contribute to the epigenetic information carried by chromatin. These changes play an important role in the regulation of gene expression by modulating the access of regulatory factors to the DNA. The use of a combination of biochemical, genetic and structural approaches has allowed demonstration of the role of chromatin structure in transcriptional control. The structure of nucleosomes has been elucidated and enzymes involved in DNA or histone modifications have been extensively characterized. Since deregulation of epigenetic marks has been reported in many cancers, a better understanding of the underlying molecular mechanisms bears the promise that new drug targets may soon be found. The newest developments in this quickly developing field are presented in this book.
Author: Raffaele Teperino
Publisher: Springer Nature
ISBN: 3030352137
Category : Medical
Languages : en
Pages : 264
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Book Description
The genotype/phenotype dichotomy is being slowly replaced by a more complex relationship whereby the majority of phenotypes arise from interactions between one’s genotype and the environment in which one lives. Interestingly, it seems that not only our lives, but also our ancestors’ lives, determine how we look. This newly recognized form of inheritance is known as (epi)genetic, as it involves an additional layer of information on top of the one encoded by the genes. Its discovery has constituted one of the biggest paradigm shifts in biology in recent years. Understanding epigenetic factors may help explain the pathogenesis of several complex human diseases (such as diabetes, obesity and cancer) and provide alternative paths for disease prevention, management and therapy. This book introduces the reader to the importance of the environment for our own health and the health of our descendants, sheds light on the current knowledge on epigenetic inheritance and opens a window to future developments in the field.
Author: Vincenzo E. A. Russo
Publisher:
ISBN:
Category : Medical
Languages : en
Pages : 716
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Book Description
Many inheritable changes in gene function are not explained by changes in the DNA sequence. Such epigenetic mechanisms are known to influence gene function in most complex organisms and include effects such as transposon function, chromosome imprinting, yeast mating type switching and telomeric silencing. In recent years, epigenetic effects have become a major focus of research activity. This monograph, edited by three well-known biologists from different specialties, is the first to review and synthesize what is known about these effects across all species, particularly from a molecular perspective, and will be of interest to everyone in the fields of molecular biology and genetics.
Author: Heth Roderick Turnquist
Publisher: Frontiers Media SA
ISBN: 2889715345
Category : Medical
Languages : en
Pages : 165
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Book Description
Author: Indra K. Vasil
Publisher: Springer Science & Business Media
ISBN: 9401726795
Category : Science
Languages : en
Pages : 603
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Book Description
The 10th IAPTC&B Congress, Plant Biotechnology 2002 and Beyond, was held June 23-28, 2002, at Disney's Coronado Springs Resort, in Orlando, Florida, USA. It was attended by 1,176 scientists from 54 countries. The best and brightest stars of international plant biotechnology headlined the scientific program. It included the opening address by the President of the IAPTC&B, 14 plenary lectures, and 111 keynote lectures and contributed papers presented in 17 symposia covering all aspects of plant biotechnology. More than 500 posters supplemented the formal program. The distinguished speakers described, discussed and debated not only the best of science that has been done or is being done, but also how the power of plant biotechnology can be harnessed to meet future challenges and needs. The program was focused on what is new and what is exciting, what is state of the art, and what is on the cutting edge of science and technology. In keeping with the international mandate of the IAPTC&B, 73 of the 125 speakers were from outside the United States, representing 27 countries from every region of the world. The 10th IAPTC&B Congress was a truly world-class event. The IAPTC&B, founded in 1963 at the first international conference of plant tissue culture organized by Philip White in the United States, currently has over 1,500 members in 85 countries. It is the largest, oldest, and the most comprehensive international professional organization in the field of plant biotechnology. The IAPTC&B has served the plant biotechnology community well through its many active national chapters throughout the World, by maintaining and disseminating a membership list and a website, by the publication of an official journal (formerly the Newsletter), and by organizing quadrennial international congresses in France (1970), the United Kingdom (1974), Canada (1978), Japan (1982), the United States (1963, 1986, 2002), The Netherlands (1990), Italy (1994), and Israel (1998). In addition, the IAPTC&B has a long tradition of publishing the proceedings of its congresses. Individually, these volumes have provided authoritative quadrennial reports of the status of international plant biotechnology. Collectively, they document the history of plant biotechnology during the 20th century. They are indeed a valuable resource. We are pleased to continue this tradition by publishing this proceedings volume of the 10th IAPTC&B Congress. Regrettably, we are not able to publish seven of the lectures in full (only their abstracts are included). The American and Canadian chapters of the IAPTC&B, the Plant Section of the Society for In Vitro Biology, and the University of Florida hosted the 10th IAPTC&B Congress. The Congress was a true partnership between academia and industry, and was generously supported by both groups (see list of donors/sponsors on back cover). A number of prominent international biotechnology companies and publishers participated in the very successful Science and Technology Exhibit (see accompanying list of exhibitors) The IAPTC&B awarded 84 fellowships to young scientists from 31 countries (see accompanying list of fellowship recipients) to support their participation in the Congress.
Author: L. Joseph Su
Publisher: Springer
ISBN: 1447166787
Category : Medical
Languages : en
Pages : 327
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Book Description
This book examines the toxicological and health implications of environmental epigenetics and provides knowledge through an interdisciplinary approach. Included in this volume are chapters outlining various environmental risk factors such as phthalates and dietary components, life states such as pregnancy and ageing, hormonal and metabolic considerations and specific disease risks such as cancer cardiovascular diseases and other non-communicable diseases. Environmental Epigenetics imparts integrative knowledge of the science of epigenetics and the issues raised in environmental epidemiology. This book is intended to serve both as a reference compendium on environmental epigenetics for scientists in academia, industry and laboratories and as a textbook for graduate level environmental health courses. Environmental Epigenetics imparts integrative knowledge of the science of epigenetics and the issues raised in environmental epidemiology. This book is intended to serve both as a reference compendium on environmental epigenetics for scientists in academia, industry and laboratories and as a textbook for graduate level environmental health courses.
Author:
Publisher: Academic Press
ISBN: 0128112344
Category : Science
Languages : en
Pages : 382
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Book Description
Transgenic Plants, Volume 86, the latest release in the series Advances in Botanical Research, brings together information needed by many teachers, researchers and managers who have to consider biotechnology from a scientific or legal point-of-view. It presents authors who bring their long personal experience on a given subject. Although the subjects are technical in nature, the take-home message of each chapter is understandable by non-specialists. Encompasses various aspects of the GMO debate (its historical background, current status, recent research outcomes, potential future developments) Written by highly competent authors from all continents Based on facts and written in a dispassionate and non-polemical tone
Author: Frederick W. Alt
Publisher: Elsevier
ISBN: 0080475078
Category : Medical
Languages : en
Pages : 306
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Book Description
Advances in Immunology, a long established and highly respected serial, presents current developments as well as comprehensive reviews in immunology. Articles address the wide range of topics that comprise immunology, including molecular and cellular activation mechanisms, phylogeny and molecular evolution, and clinical modalities. Edited and authored by the foremost scientists in the field, each volume provides up-to-date information and directions for future research.
