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Author: Moshe Szyf Publisher: Springer Science & Business Media ISBN: 038727443X Category : Medical Languages : en Pages : 253
Book Description
NA methylation has bewildered molecular biologists since Hotchkiss discovered it almost six decades ago (Hotchkiss RDJ. Biol Cem 1948; 175:315-332). The fact that the chemical structure of our D genome consists of two components that are covalently bound, the genetic information that is replicated by the DNA replication machinery ana DNA methylation that is maintainea by independent enzymatic machinery, has redictably stimulated the imagination and curiosity of generations of mo Edular biologists. An obvious question was whether DNA methylation was a bearer of additional information to the genetic information and what was the nature of this information? It was tempting to speculate that DNA me thylation applied some form of control over programming of the genome s expression profile. Once techniques to probe the methylation profile of whole genomes as well as specific genes became available, it became clear that DNA methylation patterns are gene and tissue specific and that patterns of gene expression correlate with patterns of methylation. DNA methylation pat terns emerged as the only component of the chemical structure of DNA that exhibited tissue and cell specificity. This data seemingly provided an attrac tively simple explanation for the longstanding dilemma of how could one identical genome manifest itself in so many different forms in multicellular organisms? The DNA methylation pattern has thus become the only known factor to confer upon DNA a unique cellular identity.
Author: Moshe Szyf Publisher: Springer Science & Business Media ISBN: 038727443X Category : Medical Languages : en Pages : 253
Book Description
NA methylation has bewildered molecular biologists since Hotchkiss discovered it almost six decades ago (Hotchkiss RDJ. Biol Cem 1948; 175:315-332). The fact that the chemical structure of our D genome consists of two components that are covalently bound, the genetic information that is replicated by the DNA replication machinery ana DNA methylation that is maintainea by independent enzymatic machinery, has redictably stimulated the imagination and curiosity of generations of mo Edular biologists. An obvious question was whether DNA methylation was a bearer of additional information to the genetic information and what was the nature of this information? It was tempting to speculate that DNA me thylation applied some form of control over programming of the genome s expression profile. Once techniques to probe the methylation profile of whole genomes as well as specific genes became available, it became clear that DNA methylation patterns are gene and tissue specific and that patterns of gene expression correlate with patterns of methylation. DNA methylation pat terns emerged as the only component of the chemical structure of DNA that exhibited tissue and cell specificity. This data seemingly provided an attrac tively simple explanation for the longstanding dilemma of how could one identical genome manifest itself in so many different forms in multicellular organisms? The DNA methylation pattern has thus become the only known factor to confer upon DNA a unique cellular identity.
Author: Michael Lübbert Publisher: Springer Science & Business Media ISBN: 3642384048 Category : Medical Languages : en Pages : 332
Book Description
The growing knowledge about disturbances of epigenetic gene regulation in hematopoietic stem cell disorders is now being translated into treatment approaches that target the epigenetic defects pharmacologically. This book first presents the latest evidence regarding the epigenetic regulation of hematopoietic stem cell differentiation and hemoglobin production. The significance of DNA methylation abnormalities in hematopoietic disorders and of epigenetic disturbances in lung cancer and other solid tumors is then discussed. A major part of the book, however, relates specifically to the translation of basic research and drug development to clinical applications, and in this context both present and future clinical strategies are considered. Individual chapters are devoted to the use of DNA hypomethylating agents and chromatin-modifying agents, and the treatment of hematologic malignancies and solid tumors by means of epigenetic agents is discussed in detail.
Author: Antonio Giordano Publisher: John Wiley & Sons ISBN: 1118005732 Category : Medical Languages : en Pages : 202
Book Description
Cancer Epigenetics: Biomolecular Therapeutics in Human Cancer is the only resource to focus on biomolecular approaches to cancer therapy. Its presentation of the latest research in cancer biology reflects the interdisciplinary nature of the field and aims to facilitate collaboration between the basic, translational, and clinical sciences.
Author: Steven Gray Publisher: Elsevier ISBN: 0323917151 Category : Medical Languages : en Pages : 773
Book Description
Epigenetic Cancer Therapy, Second Edition provides a comprehensive discussion of healthy and aberrant epigenetic biology, along with new discoveries to improve our understanding of cancer epigenetics and therapeutics. The book encompasses large-scale intergovernmental initiatives, as well as recent findings across cancer stem cells, rational drug design, clinical trials, and chemopreventative strategies. As a whole, the work articulates and raises the profile of epigenetics as a therapeutic option in the future management of cancer. Since the publication of the first edition of this book, the field of epigenetics has undergone significant change. New epigenetic therapies have been designed and approved for clinical use. Our knowledge of the plasticity of the epigenome in cancer and disease has expanded dramatically, with increasing evidence linking pollution to epigenetic changes in cancer development. This second edition has been fully updated to address these changes, along with promising therapeutic programs such as CRISPR/Cas9 mediated approaches, CAR-T based therapies, epigenetic priming, histone modifications, and similar, transformative advances across synthetic biology and cellular engineering. Concisely summarizes the therapeutic implications of recent, large-scale epigenome studies Covers new findings in the interplay between cancer stem cells (CSCs) and drug resistance, thus demonstrating that epigenetic machinery is a candidate target for the eradication of these CSCs Provides a fully updated resource on new topics, including the epitranscriptome, oncohistones, single cell analysis, epigenetic priming, CRISPR therapy, CAR-T therapy, and epigenetics and pollution Features chapter contributions from leading experts in the field
Author: Shelley L. Berger Publisher: Springer Science & Business Media ISBN: 354037633X Category : Science Languages : en Pages : 223
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: Atsushi Kaneda Publisher: Springer ISBN: 3319597868 Category : Medical Languages : en Pages : 616
Book Description
This book will focus on DNA and histone methylation in epigenetics and describe how it is involved in the molecular mechanisms responsible for the development of cancer. Chapters will summarize the current knowledge of the molecular basis of DNA and histone methylation and explain how it is involved in cancer, describe the features of DNA and histone methylation associated with particular types of cancer, diagnostic/therapeutic applications, and future directions of DNA and histone methylation as cancer targets.
Author: Trygve Tollefsbol Publisher: CRC Press ISBN: 1420045806 Category : Medical Languages : en Pages : 472
Book Description
During the past few decades, it has become increasingly apparent that heredity is not the sole determining factor in disease development, such as cancer. This landmark work covers a wide array of aspects in the relatively new area of epigenetics, ranging from its role in the basic mechanisms of tumorigenesis, to the newest epigenetic drugs being de
Author: Fazlul H. Sarkar Publisher: Springer Science & Business Media ISBN: 9400766122 Category : Medical Languages : en Pages : 295
Book Description
Overall, this book illustrates the complexities of the regulation and deregulation of genes mediated through epigenetics in the development and progression of human malignancies. All the articles have been carefully chosen to represent several cancer systems with state of our knowledge on the role of epigenetic deregulation of microRNAs (miRNAs) and their target mRNAs along with epigenetic deregulation of mRNAs. This book also illustrates the role of several dietary agents, collectively called nutraceuticals or natural agents in modulating the epigenetic reprogramming of miRNAs and mRNAs for the prevention and/or treatment of human malignancies. It is well known that genetic aberrations, especially inherited through parents (somatic genetic alterations) contribute to the development of less than 10% of all cancer yet epigenetic alterations in genes especially through selective methylation and acetylation appears to be responsible for the development and progression of the vast majority of all cancers. Therefore, understanding the role of epigenetics in the regulation of genes especially through deregulated expression of miRNAs as presented in this book will allow scientists to devise targeted therapeutic strategies for re-expression of the lost genes or down-regulate the genes that are over-expressed in order to eradicate cancer. It is hoped that targeting epigenetics will not only target cancer cells but it will also target the tumor microenvironment (more like the entire tumor environment such as the entire host) for achieving better treatment outcomes for patients diagnosed with cancer which will lead to achieve the long-term objective for complete eradication of cancer. This book contains fifteen chapters which begins with the concept of systems and network biology for investigating the epigenetics of cancer followed by a series of articles on the role of miRNAs and their target genes in the biology of pancreatic cancer and other cancers such as breast, kidney, prostate and and colon. Since it is becoming increasingly clear that cancer stem cells (CSCs) are important in the development and progression of cancer, and CSCs are important in therapeutic resistance, treatment failure and tumor recurrence, thus the importance of CSCs and epigenetics has been highlighted by a very timely article on epigenetic variations of stem cell markers in cancer including miRNAs. Moreover, just targeting heterogeneous cancer cell populations may not be optimal to eradicate tumors and for which one must take a holistic approach for developing drugs that could also target the tumor microenvironment and tumor dormancy that are regulated through epigenetics. Keeping abreast with this thought process the concluding chapter provides a concept towards curative cancer therapy with maspin, which could be a unique window of opportunity to target tumor dormancy. Therefore, it suggest that targeting the tumor dormancy and the tumor microenvironment using novel therapeutics specifically by targeting epigenetics would become the future of medicine.
Author: Pui Chi Flora Chik Publisher: ISBN: Category : Languages : en Pages :
Book Description
"Cancer cells have aberrant DNA methylation patterns which are characterized by hypomethylation of a large set of promoters and hypermethylation of tumor suppressor genes. The dynamic nature of the epigenome makes it a valuable target for therapeutic interventions. This thesis focuses on understanding the use of various inhibitors towards DNA methylation-related proteins and their respective anti-cancer activities at both global and gene-specific levels. The widely used demethylating agent 5-azacytidine and 5-aza-2'-deoxycytidine (5-azaCdR) are FDA-approved drugs for the treatment of myelodysplastic syndrome. However, these nucleoside analogs which trap the DNA methyltransferases (DNMTs) are non-specific. Studies have shown that 5-azaCdR induced pro-metastatic genes and caused long distance metastasis. This raises serious safety concerns for their clinical use. On the contrary, targeting the DNMTs individually or in combination did not result in dramatic induction of pro-metastatic genes as with 5-azaCdR treatment. In particular, single DNMT1-specific inhibition resulted in maximum growth suppression when compared to inhibition of all three major DNMTs, while not increasing cell invasiveness. DNMT1 has been shown to be important for cancer growth. Our study supports the idea that DNMT1 has a major role in cancer over the other DNMTs and that DNMT1 inhibitors could be effective anti-cancer drugs. 5-azaCdR has nevertheless been proven to be a potent suppressor of cancer growth. We tested the idea of a combinatorial treatment that may minimize its side-effects on cell invasion while maintaining its growth suppressor effects. The methyl-CpG binding protein 2 (MBD2) protein has been shown to demethylate pro-metastatic genes. Its inhibition in concurrent with 5-azaCdR treatment synergistically suppressed cancer growth, while reversed the 5-azaCdR-induced invasion. In order to have a deeper understanding of the impact of the treatments, microarrays studies on the methylome and transcriptome of the treated cells were carried out. Bioinformatics analysis indicated that the combined treatment suppressed gene networks that were involved in cell mobility, while synergistically enhanced gene networks that were involved in cell death. This data indicate that combining 5-azaCdR treatment with MBD2 inhibition results in more potent anti-cancer effects than either treatment alone. In order to explore the currently available drugs that inhibit MBD2, we tested the combination of S-adenosylmethionine (SAM) with 5-azaCdR on the same cancer cell lines. SAM remethylated gene promoters of pro-metastatic genes and repressed 5-azaCdR-induced invasion similarly to MBD2 inhibition. We then investigated the relationship between SAM and MBD2 downregulation and observed hypermethylation on both CpG and non-CpG sites in the MBD2 promoter upon SAM treatment. Interestingly, inhibition of MBD2 using short interference RNA also resulted in hypermethylation of its own promoter. This observation suggested that SAM treatment could directly downregulate MBD2 expression, which is further downregulated through a feedback loop. These results also suggested that SAM treatment could have a direct effect on MBD2 promoter, which in turn affects multiple MBD2 targets that are involved in invasion. Together, the data from this thesis support the idea that targeting the epigenome could be a highly efficacious anti-cancer therapy and that combining drugs that target DNA methylation could increase the potency over individual treatments." --
Author: Renato Paro Publisher: Springer Nature ISBN: 3030686701 Category : Science Languages : en Pages : 215
Book Description
This open access textbook leads the reader from basic concepts of chromatin structure and function and RNA mechanisms to the understanding of epigenetics, imprinting, regeneration and reprogramming. The textbook treats epigenetic phenomena in animals, as well as plants. Written by four internationally known experts and senior lecturers in this field, it provides a valuable tool for Master- and PhD- students who need to comprehend the principles of epigenetics, or wish to gain a deeper knowledge in this field. After reading this book, the student will: Have an understanding of the basic toolbox of epigenetic regulation Know how genetic and epigenetic information layers are interconnected Be able to explain complex epigenetic phenomena by understanding the structures and principles of the underlying molecular mechanisms Understand how misregulated epigenetic mechanisms can lead to disease
Author: Moshe Szyf
Author: Moshe Szyf
Author: Michael Lübbert
Author: Antonio Giordano
Author: Steven Gray
Author: Shelley L. Berger
Author: Atsushi Kaneda
Author: Trygve Tollefsbol
Author: Fazlul H. Sarkar
Author: Pui Chi Flora Chik
Author: Renato Paro