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Epigenetic Regulation in Overcoming Chemoresistance, Volume 19, explains how epigenetic agents can enhance the chemotherapy sensitivity of diverse types of cancers. The book provides a comprehensive delineation and the recent development of the scientific studies on the epigenetic regulation in enhancing chemo-sensitivity. In addition, it discusses several topics such as DNA methyltransferase inhibitors (DNMTi), Histone deacetylases inhibitors (HDACi), Histone lysine demethylases inhibitors (HDMi), Histone lysine methyltransferases inhibitors (HMTi) and drugs regulating the microRNA, long non-coding RNA (lncRNA) or RNA methylation. Finally, recent and future developments of the field of epigenetic regulation are explored. This is a valuable resource for cancer researchers, clinicians, graduate students and several members of biomedical field who are interested in learning about epigenetic regulation methods to reverse chemo-resistance in cancers. - Presents detailed diagrams of the mechanisms of epigenetic regulation for easy consult - Encompasses multiple clinical trial summary diagrams to help readers quickly and clearly get information from clinical trials - Provides future perspectives in each section to inspire readers to use epigenetic regulation to overcome chemo-resistance
The link between the pineal gland and cancer is a rapidly emerging research field due to promising experimental and clinical trials with melatonin. The pineal gland acts as a transducer of environmental light to regulate rhythmic processes, including reproductive function in seasonally breeding animals and the entrainment of circadian rhythms, such as the sleep-wake cycle, in man. This book elucidates the physiological significance of the pineal gland and surveys phenomena and mechanisms of pineal - tumor interaction at the neuroendocrine, neuroimmune, neural, and molecular levels. Yet unidentified low-molecular-weight pineal substances with tumor-inhibiting capacity, a possible involvement of melatonin in electromagnetic field effects on cancer, and the oncotherapeutic potential of melatonin are also addressed. The encouraging results should incite further research to elucidate the exact nature of the link between the pineal gland and cancer for the benefit of patients.
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.
Chemotherapy is one of the major treatment options for cancer patients; however, the efficacy of chemotherapeutic management of cancer is severely limited by multidrug resistance, in that cancer cells become simultaneously resistant to many structurally and mechanistically unrelated drugs. In the past three decades, a number of mechanisms by which cancer cells acquire multidrug resistance have been discovered. In addition, the development of agents or strategies to overcome resistance has been the subject of intense study. This book contains comprehensive and up-to-date reviews of multidrug resistance mechanisms, from over-expression of ATP-binding cassette drug transporters such as P-glycoprotein, multidrug resistance-associated proteins, and breast cancer resistance p- tein to the drug ratio-dependent antagonism and the paradigm of cancer stem cells. The book also includes strategies to overcome multidrug resistance, from the development of compounds that inhibit drug transporter function to the modulation of transporter expression. In addition, this book contains techniques for the detection and imaging of drug transporters, methods for the investigation of drug resistance in animal models, and strategies to evaluate the efficacy of resistance reversal agents. The book intends to provide a state-of-the-art collection of reviews and methods for both basic and clinician investigators who are interested in cancer multidrug resistance mechanisms and reversal strategies. Tianjin, China Jun Zhou v Contents Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix 1 Multidrug Resistance in Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Bruce C. Baguley 2 Multidrug Resistance in Oncology and Beyond: From Imaging of Drug Efflux Pumps to Cellular Drug Targets . . . . . . . . . . . . . . . . . . . . . . . . . .
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.
This work covers the pathophysiology of cancer, exploring the difficulty of optimal treatment due to the complexity and diversity of cancer types. The search for distinctive molecular biology characteristics of tumor cells is especially relevant in the identification of overexpressed receptors and proteins that can be used as a target for cancer treatment. We highlight the main therapeutic modalities, particularly conventional systemic chemotherapy, addressing its mechanisms of action, therapeutic classes and even the toxic effects. We also describe the main tumor markers, their importance in the diagnosis and treatment of cancer, and the specificity of tumor cells. The first chapters serve as an introduction to the central topic of this book, targeted therapy. Key aspects of target therapy, such as classes of drugs, immunotherapy, monoclonal antibodies, checkpoint inhibitors, cancer vaccines and tyrosine kinase inhibitors are presented, and, for each one, the benefits, as well as the adverse effects are reported. Chapter 6 compares conventional systemic chemotherapy and targeted therapy, identifies the risks and benefits and also the eligibility criteria for patient care. The possibility of targeted therapy replacing conventional chemotherapy is discussed while reviewing studies that demonstrate the benefits of combining both types of treatment. Finally, the introduction of pharmaceutical nanotechnology to improve antineoplastic agents is addressed in the last chapter and sets the direction for future research in cancer treatment. This is a valuable resource for many health professionals including physicians, pharmacists, nurses, researchers and students interested in the field of oncology.
Strategies for Overcoming Chemotherapy Resistance in Cervical Cancer: From Molecular Insights to Precision Solutions, Volume 21 highlights different strategies to reverse chemotherapy resistance in cervical cancer. The book puts a strong focus on strategies to reverse chemotherapy resistance as well as strategies for early detection of the resistance, enhancing precision oncology in terms of patient care and maximizing patient management. The book also looks at virally induced resistance to chemotherapy and recommends combination therapies that can maximize the reversal of this resistance.In 10 chapters, the book not only gives an overview of cervical cancer and chemotherapy as treatment, but also investigates resistance to chemotherapy and treatment for resistance. It defines treatment mechanisms, options, and limitations to beat chemotherapy resistance and the reversal of the resistance mechanisms. It gives insights into future directions of cervical cancer treatment using epigenetic silencing, chemotherapy splicing, the involvement of MicroRNAs to chemotherapy resistance, and the application of Artificial Intelligence. - Discusses strategies to reverse and detect resistance to chemotherapy at an early stage - Investigates the applications of Artificial Intelligence in the study of cervical chemotherapy resistance - Presents research and applications developed to overcome cancer resistance
Epigenetic Regulation of Cancer in Response to Chemotherapy, Volume 158 of the Advances in Cancer Research series, highlights new advances in the field, with this new volume presenting chapters on timely topics, including Epigenetically Programmed Resistance to Chemotherapy and Promotion of Immune Evasion in Cancer, A Role for the Epigenome in Cancer Cell Drug Tolerance, Histone Methylation and X Chromosomal Genes in Metastasis of Breast Cancer, Targeting Epigenetic Regulation Using Small Molecule Inhibitors, Histone Deacetylase Inhibitors as Sanguine Epigenetic Therapeutics against Pugnacious Lung Cancer, From ecology to oncology: To understand cancer stem cell dormancy, ask a Brine shrimp (Artemia), and more. Additional chapters cover Predictive Models of Chemoresistance Generated by Crunching the Public Drug Screen, Epigenomic and Genomic Profiling Datasets via Regression-, Machine Learning, and Knowledge-Based Methods, Probing on the Mechanisms of lncRNAs on Cancer Drug Resistance, Drug Tolerant Persister Cells in Cancer: Current Knowledge and Therapeutic Perspectives, and much more. - Provides the authority and expertise of leading contributors from an international board of authors - Presents the latest release in the Advances in Cancer Research series - Includes the latest information on the Epigenetic Regulation of Cancer in Response to Chemotherapy
Candidate gene based studies have identified a handful of aberrant CpG DNA methylation events in prostate cancer (Brooks et al. 1998; Yegnasubramanian et al. 2004). However, large scale DNA methylation profiles have not been examined for normal prostates or prostate tumors. Additionally, the mechanisms behind these DNA methylation alterations are unknown. In this thesis, I describe the results of my efforts to better understand these previously unexplored areas of biology. For the study presented in this thesis, I quantitatively profiled 95 primary prostate tumors and 86 healthy prostate tissue samples for their DNA methylation levels at 26,333 CpGs representing 14,104 gene promoters by using the Illumina HumanMethylation27 platform. When the profiles of the prostate tissue samples were compared, I observed a substantial number of tumor-specific DNA methylation alterations. A 2-class Significance Analysis of this dataset revealed 5,912 CpG sites with increased DNA methylation and 2,151 CpG sites with decreased DNA methylation in tumors (FDR
In recent years, the field of epigenetics has grown significantly, driving new understanding of human developmental processes and disease expression, as well as advances in diagnostics and therapeutics. As the field of epigenetics continues to grow, methods and technologies have multiplied, resulting in a wide range of approaches and tools researchers might employ. Epigenetics Methods offers comprehensive instruction in methods, protocols, and experimental approaches applied in field of epigenetics. Here, across thirty-five chapters, specialists offer step-by-step overviews of methods used to study various epigenetic mechanisms, as employed in basic and translational research. Leading the reader from fundamental to more advanced methods, the book begins with thorough instruction in DNA methylation techniques and gene or locus-specific methylation analyses, followed by histone modification methods, chromatin evaluation, enzyme analyses of histone methylation, and studies of non-coding RNAs as epigenetic modulators. Recently developed techniques and technologies discussed include single-cell epigenomics, epigenetic editing, computational epigenetics, systems biology epigenetic methods, and forensic epigenetic approaches. Epigenetics methods currently in-development, and their implication for future research, are also considered in-depth. In addition, as with the wider life sciences, reproducibility across experiments, labs, and subdisciplines is a growing issue for epigenetics researchers. This volume provides consensus-driven methods instruction and overviews. Tollefsbol and contributing authors survey the range of existing methods; identify best practices, common themes, and challenges; and bring unity of approach to a diverse and ever-evolving field. - Includes contributions by leading international investigators involved in epigenetic research and clinical and therapeutic application - Integrates technology and translation with fundamental chapters on epigenetics methods, as well as chapters on more novel and advanced epigenetics methods - Written at verbal and technical levels that can be understood by scientists and students alike - Includes chapters on state-of-the-art techniques such as single-cell epigenomics, use of CRISPR/Cas9 for epigenetic editing, and epigenetics methods applied to forensics