In the post human-genome project era, cancer specific genomic maps are redesigning tumor taxonomy by evolving from histopathology to molecular pathology. The success of a cancer drug today is fundamentally based on the success in identifying target genes that control beneficial pathways. The overwhelming power of genomics and proteomics has enlightened researchers about the fact that the PI3K-mTOR pathway is the most commonly up-regulated signal transduction pathway in various cancers, either by virtue of its activation downstream of many cell surface growth factor receptors or by virtue of its collateral and compensatory circuitry with RAS-MAPK pathway. Oncogenic signaling in the majority of solid tumors is sustained via the PI3K-AKT-mTOR pathway. Because of its prominent role in many cancer types, the PI3K-mTOR pathway has become a major therapeutic target. The volume includes two complementary parts which address the problem of etiology and disease progression and is intended to portray the very basic mechanisms of the PI3K-AKT-mTOR signaling pathway's involvement in various facets of the cancer, including stem cell renewal, cell metabolism, angiogenesis, genetic instability, and drug resistance. Significant progress has been made in recent years elucidating the molecular mechanism of cancer cell proliferation, angiogenesis, and drug-resistance in relation to the PI3K-mTOR pathway and this volume provides an in-depth overview of recent developments made in this area.

This volume presents detailed laboratory protocols for in vitro synthesis of mRNA with favorable properties, its introduction into cells by a variety of techniques, and the measurement of physiological and clinical consequences such as protein replacement and cancer immunotherapy. Synthetic techniques are described for structural features in mRNA that provide investigational tools such as fluorescence emission, click chemistry, photo-chemical crosslinking, and that produce mRNA with increased stability in the cell, increased translational efficiency, and reduced activation of the innate immune response. Protocols are described for clinical applications such as large-scale transfection of dendritic cells, production of GMP-grade mRNA, redirecting T cell specificity, and use of molecular adjuvants for RNA vaccines. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Synthetic mRNA: Production, Introduction into Cells, and Physiological Consequences is a valuable and cutting-edge resource for both laboratory investigators and clinicians interested in this powerful and rapidly evolving technology.

The annual meeting of the European Tissue Culture ., Society was held at the Castle of Zinkovy in Czechoslovakia from May 7-10,1969. Included as part of this meeting was a symposium on "Aging in Cell and Tissue Culture." This volume contains the papers presented at that symposium. The use of cell and tissue culture techniques to study the mechanism of aging is not new. For example, it has long been known that age-associated changes which occur in plasma can inhibit cell proliferation in vitro; also that the time lapse prior to cell migration from ex planted tissue fragments increases with increasing age. These are both examples of the expression in vitro of aging in vivo. More recently, attention has been focused on the occurrence of senescence in vitro. These investi gations have included studies of alterations in non dividing cell cultures, and to a somewhat greater extent, of age-related changes in the proliferative capacity of cells in vitro. For example, cells derived from human fetal lung retain many properties of normal cells including a stable normal diploid karyotype and these cultures have been shown to have a limited life-span in vitro. In addi tion, cultures derived from human adult lung show the same normal characteristics and appear to have a shorter life span than cells derived from fetal lung."

Presently, the need for methods involving separation, identification, and characterization of different kinds of cells is amply realized among immu nologists, hematologists, cell biologists, clinical pathologists, and cancer researchers. Unless cells exhibiting different functions and stages of differ entiation are separated from one another, it will be exceedingly difficult to study some of the molecular mechanisms involved in cell recognition, spe cialization, interactions, cytotoxicity, and transformation. Clinical diagno sis of diseased states and use of isolated cells for therapeutic (e. g., immu notherapy) or survival (e. g, transfusion) purposes are some of the pressing areas where immediate practical benefits can be obtained by applying cell separation techniques. However, the development of such useful methods is still in its infancy. A number of good techniques exist based either on the physical or biological properties of the cells, and these have produced some valuable results. Still others are to be discovered. Therefore, the purpose of this open-ended treatise is to acquaint the reader with some of the basic principles, instrumentation, and procedures presently in practice at various laboratories around the world and to present some typical applications of each technique to particular biological problems."

The study of life is the study of tier upon tier of interlocking homeostatic mechanisms, and the main theme of this book concerns that part of the system that ensures cellular and tissue homeostasis and thus maintains tissue mass, tissue structure and tissue function in the adult mammal. The functional existence of any adult tissue depends on the continuing control of the states of differentiation of its cells. Just as in an embryo, where cellular differentiation is initiated and controlled by the genetic responses of the cells to specific messenger molecules, so also throughout the whole of adult life does the genetic activity of the tissue cells continue to be regulated by similarly specific messenger molecules. The process of differentiation does not cease in the embryo but remains as the essential factor which ensures not only the function but also the continuing existence of the adult tissues. Thus the first problem considered here, the methods of control of cell production, cell function and cell death, is discussed in terms of the nature and mode of action of those messenger molecules which, from moment to moment, determine the states of differentiation of the tissue cells. Some of these messenger molecules are synthesized in adjacent tissues while others are synthesized within the responding tissues themselves.

This stimulating volume addresses vital questions about gene/environment interactions as they affect cell health from the prenatal period through later life. Beginning with a tour of epigenetic processes in the human body, the book assembles current theoretical and empirical developments across the discipline, among them transgenerational epigenetic inheritance, the effects of maternal nutrition on epigenetic change, and possible links between epigenetics and childhood obesity. Public health and policy aspects of the field are discussed in depth, with the understanding that much can be done to improve our epigenetic health as a species. And in this vein, contributors consider future possibilities, such as the reprogramming of genes to reverse cancer and other diseases. Included in the coverage: The role of environmental epigenetics in perinatal and neonatal development The epigenetic biomarker H2AX: from bench science to clinical trials What's the risk? Dental amalgam, mercury exposure, and human health risks throughout the lifespan Post-traumatic stress disorder: neurological, genetic, and epigenetic bases Children's exposure to alcohol, tobacco, and drugs: long-term outcomes Ethical implications of epigenetics Epigenetics, the Environment, and Children's Health Across Lifespans brings real-world knowledge and applications of this increasingly important field to public health practitioners, maternal and child health researchers, and environmental health experts.

This volume provides the latest research on circulating tumor cells aimed for cancer researchers, scientists, and molecular oncologists. It presents the basic concepts behind circulating tumor cells (CTCs), metastatic biology, and potential applications as to how CTCs can be used in diagnostic biomarkers. CTCs are cells that have detached from the primary tumor and circulate in the bloodstream. Such cells may become "seeds" for the growth of additional tumors. The field of analysis surrounding cancer metastasis has been steadily growing, and CTCs provide effective biomarkers that can be examined in peripheral blood through a minimally invasive "liquid biopsy" procedure. CTCs offer several exciting applications, not only as markers of disease progression but also as biomarkers of monitoring response to therapy and companion diagnostics for novel anticancer drug development. In recent years there has been rapid growth and worldwide developments on CTCs, which span both the basic sciences and biomedical engineering fields.

This monograph, written by well renowned breast cancer expect, Dr. Jose Russo, provides new insight on the pathobiology of breast cancer from the most current advances in the field, translational research, initiation and progression of the disease, the mechanism of invasion and metastasis and the concept of stem cells in treatment and drug resistance. The role of personalized medicine and genomic testing are also explored, which will provide a window to the future progress of cancer care.

Innovative microscopic techniques, introduced during the last two decades, have contributed much to creating a new picture of the dynamic architecture of the cell, which can now be more exactly correlated with specific biochemical and physiopathological events. These developments have led to significant advances in our understanding of the physiomorphological and pathological aspects of the secretory mechanism, as well as the pharmacologic methods used to control, experimentally, the function of exocrine and endocrine glands. The integration of new ultrastructural methods such as freeze-fracture/etching, immunocytochemistry, scanning and high-voltage electron microscopy, cytoautoradiography, etc. , has proven to be of great value when applied to the study of endocrine cells and tissues. Because information on this topic has appeared in a variety of scientific and medical journals, this book: (1) reviews the results of an integrative approach presenting a comprehensive ultrastructural account of the main aspects of the field; (2) points out gaps or controversial topics in our knowledge; and (3) outlines pertinent directions for future research. The chapters, prepared by recognized authorities in the field, present traditional information on the topic in a concise manner and, with a valuable selection of original illustrations, show what the integration of new microscopic methods can contribute to the subject in terms of new concepts. This volume will be useful to cell biologists, anatomists, embryologists, histologists, pharmacologists, pathologists, and, of course, endocrinologists. It will also be of interest to students, practitioners of medicine, and to all others dealing with clinical research and diagnosis.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

The book focuses on the understanding of molecular pathways by which normal cell progress to the definable stage of cancer. The chapters explore microbiota and chronic inflammation, multiple myeloma chemoprevention, microRNAs, cancer regulation, liquid biopsies, and angiogenesis. Recent advances of molecular risk assessment, tumor microenvironment, microneoplasia, malignant gene expressions are highlighted to provide a means and design of future cancer prevention strategies and challenges thereupon. The volume also explores various receptor drugs that are in development process with the emphasis of inhibitors used to prevent malignant gene expression. The book bridges the gap between basic science and clinical application of current knowledge of cancer and emphasizes that tumor progression and cancer metastasis are not random - treatments and cure are logical and eventual. Expertly authored and drawing from a wealth of international perspectives, Molecular Targets and Strategies in Cancer Prevention is invaluable reading for clinicians and researchers in the fields of oncology and molecular biology.

The fascinating area of Nutrigenomics describes this daily communication between diet, food and nutrients, their metabolites and our genome. This book describes how nutrition shapes human evolution and demonstrates its consequences for our susceptibility to diseases, such as diabetes and atherosclerosis. Inappropriate diet can yield stress for our cells, tissues and organs and then it is often associated with low-grade chronic inflammation. Overnutrition paired with physical inactivity leads to overweight and obesity and results in increased burden for a body that originally was adapted for a life in the savannas of East Africa. Therefore, this textbook does not discuss a theoretical topic in science, but it talks about real life, and our life-long "chat" with diet. We are all food consumers, thus each of us is concerned by the topic of this book and should be aware of its mechanisms. The purpose of this book is to provide an overview on the principles of nutrigenomics and their relation to health or disease. We are not aiming to compete with more comprehensive textbooks on molecular nutrition, evolutionary biology, genomics, gene regulation or metabolic diseases, but rather will focus on the essentials and will combine, in a compact form, elements from different disciplines. In order to facilitate the latter, we favor a high figure-to-text ratio following the rule "a picture tells more than thousand words". The content of this book is based on the lecture course "Nutrigenomics", which is held since 2003 once per year by Prof. Carlberg at the University of Eastern Finland in Kuopio. The book is subdivided into three sections and twelve chapters. Following the "Introduction" there are sections on the "Molecular genetic basis" and the "Links to disease", which take a view on nutrigenomics from the perspective of molecular mechanisms or from the causes of metabolic diseases, respectively. Besides its value as a textbook, Nutrigenomics will be a usefull reference for individuals working in biomedicine.

Ribonucleic acid (RNA) binding proteins currently number in the thousands and defects in their function are at the heart of diseases such as cancer and neurodegeneration. RNA binding proteins have become implicated in the intricate control of surprisingly diverse biological settings, such as circadian rhythm, stem cell self-renewal, oncogenesis and germ cell development. This book surveys a range of genome-wide and systems approaches to studying RNA binding proteins, the importance of RNA binding proteins in development, cancer and circadian rhythm.

This volume, with contributions from the most recognized experts in preventive strategies in breast cancer, presents the accepted as well as the novel ideas that have been introduced for the prevention of breast cancer. There is no single preventive agent that can stop the incidence of breast cancer-the malignant disease most frequently diagnosed in women of all races and nationalities. Furthermore, its incidence around the globe is increasing in industrialized countries. The worldwide incidence of breast cancer has increased 30-40% since the 1970s, reaching an excess of 1,390,000 new cases and a mortality of more than 460,000 cases in 2015. Therefore, what is needed is the development of rational strategies for the prevention of this fatal disease.

This volume covers the topics presented at the 3rd International Conference on Tumor Microenvironment and Cellular Stress by an international community of researchers. The conference brings together scientists to discuss different cellular and animal models of tumor microenvironment study and identify common pathways that are candidates for therapeutic intervention; stimulate collaboration between groups that are more focused on elucidation of biochemical aspects of stress biology (e.g., HIF regulation) and groups that study the pathophysiological aspects of stress pathways or engaged in drug discovery; and critically evaluate novel targets for imaging or therapeutic intervention that would be of use to the tumor microenvironment community and pharmaceutical industry.

This book provides readers an extensive overview of recent progress in basic and clinical research on cancer immunotherapy. Thanks to rapid advances in molecular biology and immunology, it has become increasingly evident that cancer growth is influenced by host immune responses. With the success of a number of clinical trials, immunotherapy has become a promising treatment modality of cancer. This book covers five major topics, including monoclonal antibodies, biological response modifiers, cancer vaccines, adoptive cellular therapy and oncolytic viruses. It also examines the combination of different immune strategies as well as the combination of immunotherapy with other treatments to increase anti-tumor effects. Through the comprehensive discussion of the topic, the book sheds valuable new light on the treatment of tumors.

This volume provides a thorough overview of the Wilms' Tumour Gene (WT1). The book begins with three review chapters that cover the involvement of WT1 in pediatric cancer, kidney disease, and tissue development and homeostasis. The next few chapters discuss cell marking and lineage tracing, epicardial cell methodology, colony forming assays for bone marrow stem cells, angiogenesis assays and zebrafish tools. The next group of chapters explores the latest tools in genomics, molecular biology, and biochemistry. They discuss dissecting transcription factor function in cell free systems, ChiP seq, proteomics, RNA interactome, and multiphoton imaging of lipids, measuring the binding constants of protein-nucleic acid interactions, and bioinformatics approaches for analyzing Next Generation Sequence data. The final chapter discusses protocols for clinical trials for immune therapy using anti-WT1 peptides. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Practical and thorough, The Wilms' Tumour (WT1) Gene: Methods and Protocols is a valuable resource for anyone who is interested in the diverse methodologies used in WT1 research.

This volume provides current methods and protocols for gene and protein delivery based on both lentivirus-generated and spontaneously released nanovesicles. Lentiviral Vectors and Exosomes as Gene and Protein Delivery Tools guides readers through methods on macromolecule delivery and chapters describe the LV-based protocols of gene engineering. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Lentiviral Vectors and Exosomes as Gene and Protein Delivery Tools aims to ensure successful results in the further study of this vital field.

This volume provides readers with a wide collection of the latest and readily reproducible technical protocols available in the field of non-viral gene delivery vectors. The chapters in this book are organized into three major parts: Part I is a section on conventional bolus gene delivery vectors that introduces typical transfection approaches relying on the addition of transfectants to the cell culture medium where the cells are grown in; Part II covers stimuli-responsive bolus transfectants and topics on gene delivery complexes made of smart polymers or stimuli-responsive polymers that change according to the environment they are in and delivered by dripping into cells; Part III discusses examples of substrate-mediated gene delivery-also termed reverse transfection-and the immobilization of a gene delivery vector onto a surface as opposed to more typical bolus delivery from the medium. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and practical, Non-Viral Gene Delivery Vectors: Methods and Protocols is written for experimentalists, and is an essential part of many laboratory bookshelves. This book will help novice and professionals alike succeed in their research in this field.

Presenting topics from the basic application of molecular genetics to more complex gene expression analysis using different models of study, this detailed volume explores asthma through the lens of genetics, considered to play an essential role in the etiopathogenesis of the disease. Since asthma is a complex disease, this book is designed to provide a review of the most useful techniques with examples of their applications in specific laboratory protocols. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Molecular Genetics of Asthma serves as an ideal guide to researchers investigating this vital field of study.

The aim of this volume is to present current methodologies to predict and understand the pathogenesis of Type-1 Diabetes for clinical and non-clinical researchers. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Practical and reliable, Type-1 Diabetes: Methods and Protocols will aid researchers in using these methods to advance their own studies.

This volume details a valuable collection of protocols and reviews, such as emerging experimental and theoretical approaches. These approaches have resulted in a substantial improvement in the understanding of chromosome architecture. Chromosome Architecture: Methods and Protocols guides readers through cutting-edge interdisciplinary methods which allow for an understanding of architecture of chromosomes with exceptionally enhanced resolution, both in terms of space and time. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Chromosome Architecture: Methods and Protocols aims to ensure successful results in the further study of this vital field.

This second edition expands upon the previous volume with new and updated chapters. Auditory and Vestibular Research: Methods and Protocols, Second Edition guides readers through protocols on cell culture, tissue engineering, nanotechnology, high-throughput screening, and physiology. Chapters on physiology cover techniques that include optical coherence tomography, patch clamping, and photostimulation of caged neurotransmitters. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Auditory and Vestibular Research: Methods and Protocols, Second Edition aims to ensure successful results in the further study of this vital field.

This volume provides a comprehensive collection of classical and cutting edge protocols and techniques to examine the normal development and physiological functions of the gastrointestinal system and to model the most common digestive diseases. The chapters focus on diverse research topics including ex vivo systems to study gastrointestinal development and functions, in vivo imaging of the gastrointestinal tract, isolation and characterization of intestinal immune cells, and animal models of gastrointestinal inflammation and cancer. The Gastrointestinal Physiology and Diseases: Methods and Protocols book targets wide audience of physiologists, cell and developmental biologists, immunologists, and physician-scientists working in the field of gastroenterology and beyond. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Highly practical and clearly written, Gastrointestinal Physiology and Diseases: Methods and Protocols will serve both seasoned researchers as well as newcomers to the field and will provide a unique resource and expert guidance to modern laboratory techniques developed for examining normal functions and diseases of the gastrointestinal tract.