Epigenetics Of Cancer Prevention

Epigenetics of Cancer Prevention, Volume Ten is the first to look at epigenetics and chemoprevention together. Although there is numerous scientific data available on how epigenetics can lead to cancer and how chemoprevention can be beneficial in the treatment of, or improvement of quality of life, together they will set an advanced understanding for the reader in this upcoming field of chemoprevention influencing epigenetics. This book discusses molecular epigenetic targets of natural products, such as green tea polyphenols, curcumin and resveratrol, and organ specific epigenetic targets related to diverse types of cancer, for example prostate, colorectal, breast, lung and skin cancers. Additionally, it encompasses a discussion on research methods and limitations to study epigenetics and epigenomics of chemopreventive drugs and personalized cancer treatment with phytochemicals. The book is ideal for cancer researchers, health care professionals and all individuals who are interested in cancer prevention research and its clinical applications, especially in natural remedies. Lists natural agents, including nutraceuticals, and their effects on normal or tumor genome Addresses various epigenetic systems and mechanisms in the regulation and support of the mammalian genome Discusses how various parts of dietary phytochemicals can influence or modify epigenetic mechanisms in several types of cancer

This volume addresses the question of how knowledge of epigenetic phenomena like DNA methylation and acetylation can be applied to early cancer detection and risk assessment. The objectives of the papers include defining the terminology used in epigenetics.

This volume shares technologies that detect common epigenetic changes which are very important in the early detection, progression, and prognosis of cancer as well as the design of new therapeutic tools against cancer cells. Beginning with a bit of background on epigenetic mechanisms, Cancer Epigenetics: Risk Assessment, Diagnosis, Treatment, and Prognosis continues with cancer specific type epigenetic change, methods and technologies used for detecting epigenetic changes, factors that influence epigenetic changes in cancer, as well as a final section on future directions in the field. Written for the highly successful Methods in Molecular Biology series, chapters in this volume include the kind of detailed implementation advice that guarantees easily reproducible results. Comprehensive and practical, Cancer Epigenetics: Risk Assessment, Diagnosis, Treatment, and Prognosis provides the most up-to-date knowledge of epigenetics and its implication in cancer prevention by risk assessment and screening and cancer control by treatment.

In a simplified form, epigenetics refers to heritable changes in phenotype that are not due to changes in the underlying DNA sequence. In this book, epigenetic mechanisms of regulation and dysregulation in health and disease are explored in great depth. Detailed chapters on epigenetic processes including DNA methylation and chromatin post-translational modifications including potential interventions with DNA methyltransferase inhibitors and histone deacetylase inhibitors are explored in initial chapters. These provide a detailed overview and important background to the entire field. The book is then focussed on epigenetic mechanisms involved in various diseases including anti-inflammatory and autoimmune conditions. Important accounts relating to the effects of epigenetics in metabolic syndrome, cardiovascular disease and asthma are the focus of subsequent chapters. The role of epigenetic dysregulation in malignancy is a current topic of interest and represents an intense field of research. A large component of this book is dedicated to the analysis of aberrant epigenetic processes in carcinogenesis and cancer progression. Further, chapters are focused on emerging cancer prevention using nutritional components and anti-cancer therapies particularly with histone deacetylase inhibitors, which have already been approved for the treatment of cutaneous T-cell lymphoma. The emerging role of nanoparticle preparations, especially in the context of delivering potential epigenetic therapies to target cells in various diseases, is also explored in this book. Overall, this book encompasses a wide range of topics related to epigenetic mechanisms in health and disease and would appeal to anyone with an interest in epigenetics, chromatin biology and emerging epigenetic interventions and therapies.

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.

Cancer chemoprevention is defined as the strategy to block or slow the onset of premalignant tumors and using relatively nontoxic chemical substance. Recently, accumulating experimental evidence has suggested that epigenetic alterations are involved in cancer development. The scope of epigenetics lies on the molecular interface between genetics and environmental factors; external factors switch genes on and off by influencing how cells read the genes. DNA methylation, histone covalent modification and remodeling, miRNA-mediated gene silencing represent the major mechanisms that play important role in epigenetic control of gene expression. This thesis focused on elucidating the epigenetic mechanisms in cancer prevention by dietary phytochemicals. Nrf2 is a master regulator of the antioxidant response and xenobiotic metabolism through the regulation of a wide range of antioxidant and phase II detoxification genes. The cellular protective role of Nrf2 points its potential as a primary target in chemoprevetion. Our group has reported that within tumor development in the transgenic adenocarcinoma of mouse prostate (TRAMP) model, there is a progressive loss of expression of Nrf2 and its downstream target genes, which is associated CpG hypermethylation in the promoter region. Using TRAMP C1 cells, we demonstrated that sulforaphane is a potent demethylation agent and it restores the epigenetically silenced Nrf2 gene through DNA demethylation. JB6 cells are derived from normal skin epidermis. We found that hypermethylation of Nrf2 promoter also exists in the transformation sensitive JB6 P+ cell line. The epigenetic reactivation of the Nrf2 signaling pathway by Tanshinone IIA could potentially contribute to the attenuation of JB6 P+ cellular transformation under the challenge of TPA, a tumor promoter. On the other hand, histone modification, in particular acetylation of H3K27 residue, is implicated in the transcription activation of pro-survival, pro-proliferative, and pro-inflammatory genes following TPA treatment. Bromodomain and extraterminal domain (BET) proteins function as epigenetic reader that recognizes acetylated histone tails and recruits the transcription machinery. Our study revealed that a small molecule BET inhibitor JQ-1 exerts potent anti-cancer and anti-inflammatory effects by interfering with the core transcriptional program of neoplastic transformation. Last but not least, altered levels of miRNA have been linked to tumor malignancy due to their ability to regulate functional gene expression in carcinogenesis. Using oligonucleotide microarray approach we identified the most affected miRNAs in LNCaP cells. Then we further assessed one potential target of PEITC - miR-194 in prostate cancer cell invasiveness. Collectively, dietary phytochemicals could modulate cellular epigenetic events that in part contribute to the cancer preventive effects. Given that oxidative stress and inflammation reaction are important (micro) environmental factors in malignancy transformation, understanding the role of redox and inflammatory signaling in epigenetic regulation could bring novel insights in cancer prevention.

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.

This book explores epigenetic strategies, bridging fundamental cancer epigenetics, different paradigms in tumor genetics and translational understanding for both the clinic and improved lifestyles. The work provides target-based insights for treating different types of cancers and presents research on evolutionary epigenetics, introducing ‘Medical Epi- Anthropology’ and ‘Cancer Epi-Anthropology’. Translating multi-disciplinary research into therapeutic design is at the core of this book. Readers may explore how cancer management involves unmasking the involved networks and the interactive status of different genes to achieve the appropriate methylome based therapy. Early chapters explore fundamental aspects and brain tumours, whilst later chapters investigate breast cancer and various other cancers, and the final chapter presents an evolutionary insight in cancer epigenetics, considering that the epigene is beyond DNA methylation, RNA interference and histone modification in cancer development. This book will be of interest to researchers in different medical and scientific fields, including clinical management (diagnosis, prognosis, prediction, prevention, and guidelines), genetic education, nutrition and nutrigenomics, industrial chemistry, and drug innovation. Because of the unique bridging between science and medicine this book will also be useful as an educational and translational research package.