Our limited understanding of cellular regulatory signal-transduction-networks has been a barrier to progress in improving the overall cure-rate of human cancers. Delineation of the physiologic roles of the specific regulatory signaling components, with known association with metastatic phenotypes, is a highly promising area which will likely provide the next generation of targeted strategies in the future of molecular cancer medicine. These signaling components are likely to be used in diagnosis, prognosis, and as novel targets for therapeutic development.

This book brings together up-to-date summaries by leading cancer researchers on the major principles of cancer cell biology: survival, apoptosis, adhesion, and cell cycle deregulation. It is directed at clinicians and scientists working in the areas of experimental and molecular therapeutics, molecular medicine, translational cancer research, and bio-medical sciences in general.

This volume deals with the most advanced areas of reactivation of the cell cycle in terminally differentiated cells. Terminally differentiated cells have long been regarded as irreversibly unable to proliferate. However, this view is being overturned, with great implications for both biological knowledge and potential therapeutic applications.

The basic science is presented in detail and the potentialities for exploitation in cell replacement therapy and tissue repair are highlighted. For the first time, large parts of this research field are covered in a single resource, contributed by scientists who have given the most to its advancement in recent years. This volume will be valuable for young scientists wishing to enter this field and will serve as an authoritative reference for those already working in it.

Recent years have witnessed striking advances in research on axons at a cellular level that substantially impact our current understanding of axonal biology. Newer findings and their ramifications are critically reviewed in the 16 chapters of this volume by authors highly qualified by virtue of their scientific contributions to research areas they know and write about. Five basic areas (I to V) germane to axonal biology are highlighted, beginning with (I) signaling interactions mediating myelination, and differentiation of axonal membrane domains; (IIa) issues surrounding organization and transport dynamics of neurofilaments in axons, (IIb) mechanisms regulating microtubule organization and dynamics, misregulation of which causes axonal degeneration, and (IIc) the roles actin binding proteins play in regulating organization and functions of the actin filament system in mature and growing axons; (IIIa) myosin motor proteins and cargoes intrinsic to the axon compartment, (IIIb) mitochondrial transport motors, and imperatives governing transport dynamics and directional delivery, (IIIc) mechanisms mediating retrograde signaling associated with NGF's role in trophic-dependent neuronal survival, and (IIId) potential for impaired subcellular targeting of a -synuclein as a mechanism for accumulation of Lewy body inclusions in synucleinopathies; (IVa) occurrence and organization of discrete ribosome-containing domains in axons, (IVb) endogenous mRNAs, classes of proteins translated locally, and RNP trafficking in axons, (IVc) importance of locally synthesized nuclear encoded mitochondrial proteins for maintenance, function and survival of axons, (IVd) occurrence of RNA trafficking from glial cells to axons, and significance glial RNA transcripts may play in expression in axons and axon terminals, (IVe) RNA trafficking and localization of RNA transcripts in axonal growth cones, and signaling pathways that modulate local protein synthesis for directional elongation, and (IVf) genetic and molecular defects underlying spinal muscular atrophy, and roles that SMN gene product plays as a molecular chaperone in mRNA transport and translation; (Va) injury-induced local synthesis of a protein forming a retrograde signaling complex in axons to stimulate regeneration, and (Vb) endogenous and exogenous factors that condition axonal regenerative capacity in PNS and CNS, including injury-induced activation of specific genes governing regeneration. Emergent complexities revealed in this volume compel a major revision in the traditional conceptual model of the axon's intrinsic makeup and capacities.

Advances in Applied Microbiology, Volume 123 continues the comprehensive reach of this widely read and authoritative review source in microbiology. Users will find invaluable references and information on a variety of areas relating to the topics of microbiology.

This volume contains the proceedings of an International Sympo- sium on the Biology and Pharmacology of Tumor Cell Differentiation- held on June 29-July I, 1986 at the University of Tromso, Norway. The objective of this meeting was to bring together scientists from various disciplines to discuss recent advances in the understanding of tumor cell differentiation and to bridge the gap between experimental findings and clinical application of new knowledge. Thus the infor- mation will be of value not only to basic scientists involved in mol- ecular and cell biology, but also to pharmacologists and clinicians trying to develop the concept of tumor cell differentiation as a thera- peutic modality. Each plenary speaker and selected poster presenters were requested to submit a comprehensive, up-to-date review of recent contributions to their disciplines related to differentiation and: hematopoietic factors and leukemic cells in culture~ vitamin deriva- tives and polyamines; nucleosides and methylation; and cell interac- tions.

Rapid progress has been made in our understanding of the molecular mechanisms of cell growth and oncogenesis during the past decade. This book comprises recent results on the regulation of cell growth in normal and neoplastic tissues by growth factors including hormones, and by the activation and inactivation of oncogenes and tumor suppressor genes, respectively. Special attention has been given to the presentation of the frequently neglected close correlation between changes in signal transduction and metabolism pathways during oncogenesis.

The book provides a comprehensive review of the fundamental and practical aspects of bioanalytical support and the integral role it plays in the development of safe and efficacious biopharmaceutical drugs with speed and cost-effectiveness. The book focuses on a broad range of conventional and emerging biopharmaceutical modalities including monoclonal antibody-based therapeutics, gene therapy, cell therapy, peptides and oligonucleotides. The book starts with an introductory overview of bioanalysis showcasing the integral role it plays in understanding the drug disposition (pharmacokinetics/pharmacodynamics and immunogenicity) and the progression of bioanalytical strategy as the drug progresses through discovery and development stages of the program, taking into consideration the continually evolving regulatory landscape. The book further diversifies into individual biopharmaceutical modalities - monoclonal antibodies, antibody-drug conjugates, bispecifics, Fc-fusion proteins, gene therapies, cell therapies, peptides and oligonucleotides. The individual chapters focus on modality-specific bioanalytical assay strategies, critical reagents, assay formats, analytical platforms, associated bioanalytical challenges and mitigation strategies, industry best practices, and the latest understanding of regulatory guidance as applicable to the fast-growing biopharmaceutical landscape.

This book describes all human leukemia-lymphoma cell lines that have been established and that grow continuously under standardised in vitro conditions. These lines are derived from cells belonging to all the major hematopoietic cell lineages, i.e. B- and T-lymphocytes, natural killer cells, granulocytic cells and megakaryocytic cells. The clinical data, the culture conditions and the major phenotypic features of the cell lines are described with citations. This book is the first book describing human leukemia-lymphoma cell lines and will be of interest to scientists involved in the areas of hematology, oncology, immunology, molecular biology and cytogenetics. Cancer Cell Lines, Volumes 1-3: These 3 volumes provide a comprehensive text on the culture of established cell lines from every type of human cancer. The volumes provide a basic manual and reference resource for every cancer research scientist using human cancer cells.

This book covers the latest findings of a wide variety of viral, prokaryotic and eukaryotic macromolecular protein complexes and builds upon the solid macromolecular foundations established by previous volumes of the Subcellular Biochemistry series. Thus, an almost encyclopaedic coverage of the broad field of protein complex structure and function has been established. The 17 interesting chapters included in this book have been organised into four sections: Soluble Protein Complexes, Membrane Protein Complexes, Fibrous Protein Complexes and Viral Protein Complexes. Significant topics present here are: Fatty Acid Synthase, the Fork Protection Complex, Ribonucleotide Reductase, the Kinetochore, G proteins, the FtsEX Complex, the Kainate Receptor, the Photosystem I-antenna, the Mycobacterial Arabinofuranosyltransferases, the the Bacterial Flagellum, the Actomyosin Complex, Motile Cilia, SLS Collagen Polymorphic Structures, and the Reovirus Capsid and Polymerase. Up-dates/expansion of chapter topics present in earlier volumes are now included in chapters here, e.g., those on Ferritin-like proteins and the Multi-tRNA Synthetase. The book is richly illustrated throughout, the result of an impressive integration of structural data from X-ray crystallography and cryo-electron microscopy. The functional aspects of protein-protein interactions are also given a high priority.

Cilia: From Mechanisms to Disease Part B, Volume 176 of Methods in Cell Biology series, highlights new advances in the field, with this new volume presenting interesting chapters. Each chapter is written by an international board of authors.

Encyclopedia of Cancer, Third Edition, Three Volume Set provides a comprehensive, up-to-date overview of the multiple facets of the disease, including research, treatment and societal impact. This new edition comprises 180 contributions from renown experts who present the latest in Mechanisms, Hallmarks of Cancer, Causes of Cancer, Prevention and Control, Diagnosis and Therapy, Pathology and the Genetics of specific Cancers. Readers will find a comprehensive overview of the main areas of oncology, including etiology, mechanisms, prevention, and treatments, from basic science to clinical applications and public health, all set alongside the latest advances and hot topics that have emerged since the previous edition. Topics of interest in the field, including genomics and epigenomics, our understanding of the causes of cancer and the approaches to preventing it (e.g., HPV vaccination, role of obesity and nutrition, molecular markers of environmental exposures), new screening techniques (e.g., low-dose CT for lung cancer) and improvements in the treatment of many cancers (e.g., breast cancer, lung adenocarcinoma) are comprehensively and authoritatively presented.

Phosphoinositides play a major role in cellular signaling and membrane organization. During the last three decades we have learned that enzymes turning over phosphoinositides control vital physiological processes and are involved in the initiation and progression of cancer, inflammation, neurodegenerative, cardiovascular, metabolic disease and more. In two volumes, this book elucidates the crucial mechanisms that control the dynamics of phosphoinositide conversion. Starting out from phosphatidylinositol, a chain of lipid kinases collaborates to generate the oncogenic lipid phosphatidylinositol(3,4,5)-trisphosphate. For every phosphate group added, there are specific lipid kinases - and phosphatases to remove it. Additionally, phospholipases can cleave off the inositol head group and generate poly-phosphoinositols, which act as soluble signals in the cytosol. Volume II extends into the role of phosphoinositides in membrane organization and vesicular traffic. Endocytosis and exocytosis are modulated by phosphoinositides, which determine the fate and activity of integral membrane proteins. Phosphatidylinositol(4,5)-bisphosphate is a prominent flag in the plasma membrane, while phosphatidylinositol-3-phosphate decorates early endosomes. The Golgi apparatus is rich in phosphatidylinositol-4-phosphate, stressed cells increase phosphatidylinositol(3,5)-bisphosphate, and the nucleus has a phosphoinositide metabolism of its own. Phosphoinositide-dependent signaling cascades and the spatial organization of distinct phosphoinositide species are required in organelle function, fission and fusion, membrane channel regulation, cytoskeletal rearrangements, adhesion processes, and thus orchestrate complex cellular responses including growth, proliferation, differentiation, cell motility, and cell polarization.

Extracellular nucleic acids have recently emerged as important players in the fields of biology and the medical sciences. In the last several years, extracellular nucleic acids have been shown to be involved in not only microbial evolution as genetic elements but also to have structural roles in bacterial communities, such as biofilms. Circulating DNA and RNA have been found in human blood and expected to be useful as non-invasive markers for the diagnosis of several diseases. In addition, extracellular nucleic acids have attracted attention as active modulators of the immune system of higher organisms, including humans. This book covers nearly all of the newly developing fields related to extracellular nucleic acids, including those of basic biology, ecology and the medical sciences, and provides readers with the latest knowledge on them.

This second book of the three-volume collection "Ion Transport in Tumor Biology" helps readers gain comprehensive knowledge of the pathophysiology of cancer. The authors highlight that ion transport proteins, channels and transporters - collectively referred to as the transportome - are significantly involved in the development and progression of cancer. Nearly 90% of malignant tumor diseases originate from epithelial cells, the function of which, for the most part, is based on the transportome. This volume focuses on molecular principles by showing that dysregulated expression and/or function of ion transporters have been correlated with malignancy in the vast majority of tumor diseases. Within the story of the various chapters, the authors line out various malfunctions of the transportome and where they can be found at different stages of the metastatic cascade. The authors describe how the interactions between the tumor cells' transportome and the environment reinforce mesenchymal behaviour of cancer cells and contribute to their uncontrolled proliferation, migration, invasion, intra- and extravasation up to the formation of metastases. As part of a three-volume collection, this book will fascinate members of the active research community, as well as clinicians from the cancer field.

In the last two decades, our knowledge on regulatory peptides and their cognate receptors, most of which are members of the seven transmembrane receptor families, has increased enormously. Regulatory peptides are small proteins which, besides their hormonal functions in regulating cellular metabolism in various tissues, may also act as neurotransmitters, and thus they often carry the prefix "neuro." Many of the cognate receptors involved in transducing the peptidergic signal across the cell membrane via a family of G proteins exist in multiple forms, the number of which frequently exceeds that of the corresponding peptide ligands. In this book, various peptide-receptor systems are discussed, e.g. CRF, somatostatin, TRH, opioid peptides, vasopressin, and oxytocin. It also discusses new strategies such as "reverse physiology" to uncover new peptides and orphan receptors.

Written by world experts in astacology, this book covers a range of aspects of the biology and ecology of freshwater crayfish. With a strong focus on wild crayfish, the book studies the taxonomy and genetics of this interesting group of animals. Under examination also are crayfish growth and reproduction, with detailed illustrations; behavior and chemical ecology of crayfish; diseases of crayfish; holistic understanding of drivers for crayfish population success; and methods for the control of non-native crayfish.

Stem cells are found in almost all organisms from the early stages of development to the end of life. There are several types of stem cells and all of them may prove useful for medical research; however, each of the different types has both promise and limitations. "Somatic Stem Cells: Methods and Protocols" presents selected genetic, molecular, and cellular techniques used in somatic stem cell research and its clinical application. Chapters focus on the isolation, characterization, purity, plasticity, and clinical uses of somatic stem cells from a variety of human and animal tissues. 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.

Through and intuitive, "Somatic Stem Cells: Methods and Protocols" seeks to provides scientists with the fundamental techniques of stem cell research and its potential application in regenerative medicine.

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This volume deals with some of the multiple systems that growth factors and cytokines affect. The role of growth factors and cytokines on foetal development, in the immune and haemopoietic systems as well as in the skeletal and reproductive systems are covered. Various cancers are examined in a number of the chapters. This is the third and concluding volume of the treatise on growth factors and cytokines in health and disease.

Jointly published with INRA, Paris.
The use of haploid plants is of increasing importance in plant biology and plant breeding. This book illustrates how the advances in plant molecular and cell biology provide an exciting means for the analysis of androgenesis in terms of pollen development and the initiation of embryogenesis. It provides both an appraisal of techniques and their practical application, and is the most up-to-date source of information about the biology of gametophytes.

This text attempts to introduce the molecular biology of cell membranes to students and professionals of diverse backgrounds. Although several membrane biology books are available, they do not integrate recent knowledge gained using modern molecular tools with more traditional membrane topics. Molecular techniques, such as cDNA cloning and x-ray diffraction, have provided fresh insights into cell membrane structure and function. The great excitement today, which I attempt to convey in this book, is that molecular details are beginning to merge with physiological responses. In other words, we are beginning to understand precisely how membranes work. This textbook is appropriate for upper-level undergraduate or beginning graduate students. Readers should have previous or concurrent coursework in biochemistry; prior studies in elementary physiology would be helpful. I have found that the presentation of topics in this book is appropriate for students of biology, biochemistry, biophysics and physiology, chemistry, and medicine. This book will be useful in courses focusing on membranes and as a supplementary text in biochemistry courses. Professionals will also find this to be a useful resource book for their personal libraries.

Leading researchers and innovators describe in step-by-step detail the latest techniques that promise to significantly impact the practice of proteomics, as well as its success in developing novel clinical agents. The methods span the entire spectrum of top-down and bottom-up approaches, including microarrays, gels, chromatography, and affinity separations, and address every aspect of the human proteome, both quantitatively and qualitatively. The techniques of protein detection utilized are diverse and range from fluorescence and resonance light scattering to surface plasmon resonance and mass spectrometry. The protocols follow the successful Methods in Molecular Biology (TM) series format, each offering step-by-step laboratory instructions, an introduction outlining the principles behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.

This book covers the tremendous progress in the current understanding of the molecular physiology of voltage-gated calcium channels. This book includes unparalleled insights into structural features of calcium channels due to X-ray crystallography and cryo-EM, which in turn yielded critical information into how these channels function under normal and pathophysiological conditions, and how they interact with calcium channel therapeutics. The chapters investigate how, with the advent of high throughput genome sequencing, numerous mutations in various calcium channel genes have been identified in patients with neurological, cardiovascular, neuropsychiatric and other disorders. This is further complemented through a much larger in vivo toolkit such as knock-out and knock-in mice. The chapters further discuss the increased complexity of calcium channel physiology that arises from mRNA editing and splicing. Finally, the book also provides an overview of the updated research on calcium channel inhibitors that can be used both in vivo and in vitro, and which may serve as a spring board for new calcium channel therapeutics for human disease. Voltage-Gated Calcium Channels is useful for academic researchers at all levels in neuroscience, biophysics, cell biology and drug discovery.

This third and final volume in the "Ion Transport in Tumor Biology" collection presents novel diagnostic and therapeutic approaches in cancer based on the exploitation of ion transport proteins. The authors critically examine several transportome members, particularly Na+, K+, Ca2+, and Cl- channels, as well as organic solute carriers regarding their suitability as therapeutic targets. Synergistic effects resulting from the combined use of classical cytostatics with ion transport-inhibiting drugs are pointed out, and the capability of bispecific antibodies to function as anticancer drugs is discussed. As readers will also learn, the use of ion channel inhibitors could improve the outcome of radiotherapy because the development of radio-resistance during radiotherapeutic treatment often correlates with increases in the expression levels and conductance of ion channels. The translational topics of this volume form a bridge between biochemical research and therapeutic application. As part of a three-volume collection, this book will fascinate members of the active research community, as well as clinicians in the cancer field.