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TP53 gene mutations are present in more than half of all human cancers. The resulting proteins are mostly full-length with a single amino acid change and are abundantly expressed in cancer cells. Some of the mutant p53 proteins gain oncogenic functions (GOF) through which it actively contribute to the aberrant cell proliferation, increased resistance to apoptotic stimuli and ability to metastasize. Gain of function mutant p53 proteins can transcriptionally regulate the expression of a large plethora of target genes. This mainly occurs through the formation of oncogenic transcriptional competent complexes that include mutant p53 protein, known transcription factors, posttranslational modifiers and scaffold proteins. Mutant p53 protein can also transcriptionally regulate the expression of microRNAs, small non-coding RNAs that regulate gene expression at the posttranscriptional level. Each microRNA can putatively target the expression of hundred mRNAs and consequently impact on many cellular functions. Thus, gain of function mutant p53 proteins can exert their oncogenic activities through the modulation of both non-coding and coding regions of human genome. Over the past 3 decades, the regulation of p53 has been extensively studied. However, the regulation of mutant p53 remained largely unexplored. This snapshot focuses on recent discovery of mutant p53 GOF and regulation.
p53 in Breast Cancer: Molecular Mechanisms, Clinical Implications, and Therapeutic Targets comprehensively reviews the role of p53 in breast cancer development, progression, and treatment. It explores the multifaceted functions of p53, from its fundamental connection to breast cancer and pathway mechanisms to its influence on cancer metabolism and the impact of mutational alterations. The initial chapters discuss the complex landscape of p53's involvement in cancer metabolism, the ramifications of its mutations, and its crucial role as a tumor suppressor. The subsequent chapters review the regulatory functions of p53 in cell death, DNA repair, genomic stability, and cell cycle dynamics, highlighting its interactions with transcription factors, DNA repair enzymes, and family members p63 and p73. It further reviews the regulation of mutant p53 via post-translational modifications and delves into the approaches to combat mutated p53, highlighting targeted therapies and efforts to overcome chemoresistance. The chapters also address the role of p53 biomarkers in diagnosis and prognosis, the optimization of treatment responses, and the impact of nutrition on p53 activity. This book is an important resource for oncology and molecular biology researchers. Key Features Provides a thorough examination of the p53 gene and its crucial involvement in breast cancer. Explores the critical implications of mutational alterations in p53 on the development and progression of breast cancer. Examines the role of p53 in managing apoptosis and contributing to DNA repair and genomic stability. Discusses the complex interactions of p53 with transcription factors, DNA repair enzymes, p63, and p73. Highlights the role of p53 as a biomarker in diagnosing and predicting breast cancer prognosis.
This reference work presents the origins of cells for tissue engineering and regeneration, including primary cells, tissue-specific stem cells, pluripotent stem cells and trans-differentiated or reprogrammed cells. There is particular emphasis on current understanding of tissue regeneration based on embryology and evolution studies, including mechanisms of amphibian regeneration. The book covers the use of autologous versus allogeneic cell sources, as well as various procedures used for cell isolation and cell pre-conditioning , such as cell sorting, biochemical and biophysical pre-conditioning, transfection and aggregation. It also presents cell modulation using growth factors, molecular factors, epigenetic approaches, changes in biophysical environment, cellular co-culture and other elements of the cellular microenvironment. The pathways of cell delivery are discussed with respect to specific clinical situations, including delivery of ex vivo manipulated cells via local and systemic routes, as well as activation and migration of endogenous reservoirs of reparative cells. The volume concludes with an in-depth discussion of the tracking of cells in vivo and their various regenerative activities inside the body, including differentiation, new tissue formation and actions on other cells by direct cell-to-cell communication and by secretion of biomolecules.
Cancer cell biology research in general, and anti-cancer drug development specifically, still relies on standard cell culture techniques that place the cells in an unnatural environment. As a consequence, growing tumor cells in plastic dishes places a selective pressure that substantially alters their original molecular and phenotypic properties.The emerging field of regenerative medicine has developed bioengineered tissue platforms that can better mimic the structure and cellular heterogeneity of in vivo tissue, and are suitable for tumor bioengineering research. Microengineering technologies have resulted in advanced methods for creating and culturing 3-D human tissue. By encapsulating the respective cell type or combining several cell types to form tissues, these model organs can be viable for longer periods of time and are cultured to develop functional properties similar to native tissues. This approach recapitulates the dynamic role of cell–cell, cell–ECM, and mechanical interactions inside the tumor. Further incorporation of cells representative of the tumor stroma, such as endothelial cells (EC) and tumor fibroblasts, can mimic the in vivo tumor microenvironment. Collectively, bioengineered tumors create an important resource for the in vitro study of tumor growth in 3D including tumor biomechanics and the effects of anti-cancer drugs on 3D tumor tissue. These technologies have the potential to overcome current limitations to genetic and histological tumor classification and development of personalized therapies.
Mesenchymal stem cell-derived exosomes are at the forefront of research in two of the most high profile and funded scientific areas – cardiovascular research and stem cells. Mesenchymal Stem Cell Derived Exosomes provides insight into the biofunction and molecular mechanisms, practical tools for research, and a look toward the clinical applications of this exciting phenomenon which is emerging as an effective diagnostic. Primarily focused on the cardiovascular applications where there have been the greatest advancements toward the clinic, this is the first compendium for clinical and biomedical researchers who are interested in integrating MSC-derived exosomes as a diagnostic and therapeutic tool. - Introduces the MSC-exosome mediated cell-cell communication - Covers the major functional benefits in current MSC-derived exosome studies - Discusses strategies for the use of MSC-derived exosomes in cardiovascular therapies
This work serves as an introduction to the applications of molecular biology in the field of oncology. It provides a basic understanding of the genetic events involved in fully developed human cancer, including research into inherited and acquired gene defects initiating new neoplasms and the subsequent genetic alterations involved in tumor progression. Some of the specific topics explored include gene control, molecular therapy and antibodies, drug resistance, growth factors and receptors, and tumor biology. While intended primarily as an advanced text for oncologists, postgraduate molecular geneticists and molecular biologists, the book will certainly be of interest to other researchers who frequently encounter cancer in their practice.
Offers a comprehensive and interdisciplinary view of cutting-edge research on advanced materials for healthcare technology and applications Advanced healthcare materials are attracting strong interest in fundamental as well as applied medical science and technology. This book summarizes the current state of knowledge in the field of advanced materials for functional therapeutics, point-of-care diagnostics, translational materials, and up-and-coming bioengineering devices. Advanced Healthcare Materials highlights the key features that enable the design of stimuli-responsive smart nanoparticles, novel biomaterials, and nano/micro devices for either diagnosis or therapy, or both, called theranostics. It also presents the latest advancements in healthcare materials and medical technology. The senior researchers from global knowledge centers have written topics including: State-of-the-art of biomaterials for human health Micro- and nanoparticles and their application in biosensors The role of immunoassays Stimuli-responsive smart nanoparticles Diagnosis and treatment of cancer Advanced materials for biomedical application and drug delivery Nanoparticles for diagnosis and/or treatment of Alzheimers disease Hierarchical modelling of elastic behavior of human dental tissue Biodegradable porous hydrogels Hydrogels in tissue engineering, drug delivery, and wound care Modified natural zeolites Supramolecular hydrogels based on cyclodextrin poly(pseudo)rotaxane Polyhydroxyalkanoate-based biomaterials Biomimetic molecularly imprinted polymers
This is the ideal book for anyone contemplating starting a career in, or shifting their career to, studying the dynamics that drive cancer progression and its response to therapy. Topics include the theory and population genetics of cancers, genetic diversity within tumors (intra-tumor heterogeneity), understanding how mutant clones expand in tissues, the role of cancer stem cells in the dynamics of tumors, the evolution of metastasis, and how to improve cancer therapy by addressing the evolution of cancers in response to our interventions. There are also chapters on the patterns of cancer susceptibility in humans due to a mismatch between our modern environment and the environment in which our ancestors evolved, as well as a chapter on the evolution of cancer suppression mechanisms that have evolved in different species, particularly the large long-lived animals like elephants and whales that are better at suppressing cancers than humans. This book serves as a primer on the evolutionary and ecological theory of cancer- the framework upon which all the details of cancer may be hung. It is ideal for oncologists and cancer researchers interested in evolutionary theory, and evolutionary biologists and ecologists interested in gaining insights into cancer development and prevention.
Epigenetics is a term in biology referring to heritable traits that do not involve changes in the underlying DNA sequence of the organism. Epigenetic traits exist on top of or in addition to the traditional molecular basis for inheritance. The "epigenome" is a parallel to the word "genome," and refers to the overall epigenetic state of a cell. Cancer and stem cell research have gradually focused attention on these genome modifications. The molecular basis of epigenetics involves modifications to DNA and the chromatin proteins that associate with it. Methylation, for example, can silence a nearby gene and seems to be involved in some cancers. Epigenetics is beginning to form and take shape as a new scientific discipline, which will have a major impact on Medicine and essentially all fields of biology. Increasingly, researchers are unearthing links between epigenetics and a number of diseases. Although in recent years cancer has been the main focus of epigenetics, recent data suggests that epigenetic plays a critical role in psychology and psychopathology. It is being realized that normal behaviors such as maternal care and pathologies such as Schizophrenia and Alzheimer's might have an epigenetic basis. It is also becoming clear that nutrition and life experiences have epigenetic consequences. Discover more online content in the Encyclopedia of Molecular Cell Biology and Molecular Medicine.
DNA repair is a rapidly advancing field in biology and these systems represent a major defense mechanism against environmental and intracellular damaging agents such as sunlight, ionizing radiation, and reactive oxygen species. With contributions from eminent researchers, this book explores the basics and current trends in this critical field. Topi