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Matrix Metalloproteinase Inhibitors in Cancer Therapy
Cutting-edge investigators review the current status of the entire field, from the biology of MMPs through the current clinical studies. The authors include many leading scientists from pharmaceutical companies who present all the latest concepts and results on the preferred design strategies for MMP inhibitors, their molecular mechanisms, and their substrates. In addition, they fully describe their personal research on specific MMP inhibitors, detailing vanguard design strategies, their in vitro activity, the outcome of animal model studies and, where available, their toxicology, safety, efficacy in human clinical trials. Comprehensive and state-of-the-art, Matrix Metalloproteinase Inhibitors in Cancer Therapy offers basic and clinical investigators alike a richly informative summary of all the latest research on these powerful new drugs, and their high promise as emerging cancer therapeutics.
Bone Metastasis
A state-of-the-art review of the molecular underpinnings of bone-seeking cancers, current treatment approaches for them, and future therapeutic strategies. The authors illuminate the role of various autocrine, paracrine, and immunological factors involved in the progression and establishment of bone metastases, highlighting the physiological processes that lead to bone degradation, pain, angiogenesis, and dysregulation of bone turnover. They also discuss the various strategies that appear to have promise and are currently deployed in treatment or are at the experimental stage.
Free Energy Calculations in Rational Drug Design
Free energy calculations represent the most accurate computational method available for predicting enzyme inhibitor binding affinities. Advances in computer power in the 1990s enabled the practical application of these calculations in rationale drug design. This book represents the first comprehensive review of this growing area of research and covers the basic theory underlying the method, numerous state of the art strategies designed to improve throughput and dozen examples wherein free energy calculations were used to design and evaluate potential drug candidates.
Targets for Cancer Chemotherapy
In Targets for Cancer Chemotherapy: Transcription Factors and Other Nuclear Proteins, a panel of leading basic researchers, pharmaceutical scientists, and clinical oncologists explain in detail the therapeutically-relevant protein targets that contribute to cancer pathology and spell out their implications for cancer drug discovery and clinical application. The authors identify and illuminate selected transcription factor oncoproteins and tumor suppressors, together with nuclear proteins that are central to the phenotype of the tumor cell involved in chromatin control. The emphasis is on new targets and approaches to cancer treatment derived from the cancer cell cycle, gene control targets, and angiogenesis.
The Oncogenomics Handbook
An integrated overview of cancer drug discovery and development from the bench to the clinic, showing with broad strokes and representative examples the drug development process as a network of linked components leading from the discovered target to the ultimate therapeutic product. Following a systems biology approach, the authors explain genomic databases and how to discover oncological targets from them, how then to advance from the gene and transcript to the level of protein biochemistry, how next to move from the chemical realm to that of the living cell and, ultimately, pursue animal modeling and clinical development. Emerging cancer therapeutics including Ritux an, Erbitux, Gleevec Herceptin, Avastin, ABX-EGF, Velcade, Kepivance, Iressa, Tarceva, and Zevalin are addressed. Highlights include cancer genomics, pharmacogenomics, transcriptomics, gene expression analysis, proteomic and enzymatic cancer profiling technologies, and cellular and animal approaches to cancer target validation.
Immunotherapy of Cancer
Expert bench and clinical scientists join forces to concurrently review both the state-of-the-art in tumor immunology and its clinical translation into promising practical treatments. The authors explain in each chapter the scientific basis behind such therapeutic agents as monoclonal antibodies, cytokines, vaccines, and T-cells, and illustrate their clinical manipulation to combat cancer. Additional chapters address statistical analysis-both of clinical trials and assay evaluations-methods for the discovery of antigens, adoptive T cell therapy, and adaptive and innate immunity. The challenges in clinical trial design, the need for biomarkers of response-such as novel imaging techniques and immunologic monitoring-and the new advances and directions in cancer immunotherapy are also fully examined.
Signaling Networks and Cell Cycle Control
Leading scientists summarize the latest findings on signal transduction and cell cycle regulation and describe the effort to design and synthesize inhibiting molecules, as well as to evaluate their biochemical and biological activities. They review the relevant cell surface receptors, their ligands, and their downstream pathways. Also examined are the latest findings on the components of novel signaling networks controlling the activity of nuclear transcription factors and cell cycle regulatory molecules. Cutting-edge and highly suggestive, Signaling Networks and Cell Cycle Control: The Molecular Basis of Cancer and Other Diseases presents a wealth of information on the emerging principles of the field, as well as an invaluable guide for all experimental and clinical investigators of cell regulation and its rapidly emerging pharmacological opportunities today.
Apoptosis, Senescence and Cancer
Provides insight into established practices and research into apoptosis and senescence by examining techniques and research in the fields of cell death pathways, senescence growth arrest, drugs and resistance, DNA damage response, and other topics which still hold mysteries for researchers. This book concludes with established cancer therapies.
Proteasome Inhibitors in Cancer Therapy
A panel of leading academic and pharmaceutical investigators takes stock of the remarkable work that has been accomplished to date with proteasome inhibitors in cancer, and examines emerging therapeutic possibilities. The topics range from a discussion of the chemistry and cell biology of the proteasome and the rationale for proteasome inhibitors in cancer to a review of current clinical trials underway. The discussion of rationales for testing proteasome inhibitors in cancer models covers the role of the proteasome in NF-kB activation, the combining of conventional chemotherapy and radiation with proteasome inhibition, notably PS-341, new proteasome methods of inhibiting viral maturation, and the role of protesome inhibition in the treatment of AIDS. The authors also document the development of bortezomib (VelcadeTM) in Phase I clinical trials and in a multicentered Phase II clinical trials in patients with relapsed and refractory myeloma.
Protein Tyrosine Kinases
Leading researchers, from the Novartis group that pioneered Gleevec/GlivecTM and around the world, comprehensively survey the state of the art in the drug discovery processes (bio- and chemoinformatics, structural biology, profiling, generation of resistance, etc.) aimed at generating PTK inhibitors for the treatment of various diseases, including cancer. Highlights include a discussion of the rationale and the progress made towards generating "selective" low molecular-weight kinase inhibitors; an analysis of the normal function, role in disease, and application of platelet-derived growth factor antagonists; and a summary of the factors involved in successful structure-based drug design. Additional chapters address the advantages and disadvantages of in vivo preclinical models for testing protein kinase inhibitors with antitumor activity and the utility of different methods in the drug discovery and development process for determining "on-target" vs "off-target" effects of kinase inhibitors.
