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This text highlights seminal discoveries and also provides comprehensive and state-of the-art approach to mouse models of human patient tumors. These areas include training, basic techniques, as well as general troubleshooting. Subsequent chapters focus on the different mouse models of patient tumors including the various strains of immunodeficient mice currently available and the transplantation techniques that can be used as well as state-of-the-art imaging techniques. Practical applications of the models from drug discovery, genome analysis to personalized treatment are also covered. Written by experts in that field, each of these sections address these critical issues. A brief review of the existing literature addressing the particular topic follows in each section. Presently, there is no single source to provide information on technique and uses of mouse models of human patient tumors. Patient-Derived Mouse Models of Cancer will satisfy this need for cancer researchers, oncologists, pharmaceutical and biotechnology industry scientists as well as molecular biologists studying in vivo systems
The laboratory mouse is an important model for addressing questions in cancer biology. In recent years, the questions have become more refined, and mouse models are increasingly being used to develop and test cancer therapeutics. Thus, the need for more sophisticated and clinically relevant mouse models has grown, as has the need for innovative tools to analyze and validate them. This laboratory manual provides cutting-edge methods for generating and characterizing mouse models that accurately recapitulate many features of human cancer. The contributors describe strategies for producing genetic models, including transgenic germline models, gene knockouts and knockins, and conditional and inducible systems, as well as models derived using transposon-based insertional mutagenesis, RNA interference, viral-mediated gene delivery, and chemical carcinogens. Tissue recombination, organ reconstitution, and transplantation methods to develop chimeric, allograft, and xenograft models are covered. Approaches to characterize tumor development, progression, and metastasis in these models using state-of-the-art imaging, histopathological, surgical, and other techniques are also included. Other chapters cover the use of mouse models to test and optimize drugs in pre-, co-, and post-clinical trials. An appendix specifically addresses the use of mouse cancer models in translational studies and the integration of mouse and human clinical investigations. This manual is therefore an indispensable laboratory resource for all researchers, from the graduate level upwards, who study cancer and its treatment.
Beverly A. Teicher and a panel of leading experts comprehensively describe for the first time in many years the state-of-the-art in animal tumor model research. The wide array of models detailed form the basis for the selection of compounds and treatments that go into clinical testing of patients, and include syngeneic models, human tumor xenograft models, orthotopic models, metastatic models, transgenic models, and gene knockout models. Synthesizing many years experience with all the major in vivo models currently available for the study of malignant disease, Tumor Models in Cancer Research provides preclinical and clinical cancer researchers alike with a comprehensive guide to the selection of these models, their effective use, and the optimal interpretation of their results.
Animal Models in Cancer Drug Discovery brings forward the most cutting-edge developments in tumor model systems for translational cancer research. The reader can find under this one volume virtually all types of existing and emerging tumor models in use by the research community. This book provides a deeper insight on how these newer models could de-risk modern drug discovery. Areas covered include up to date information on latest organoid derived models and newer genetic models. Additionally, the book discusses humanized animal tumor models for cancer immunotherapy and how they leverage personalized therapies. The chapter on larger animal, canine models and their use in and their use in pre-investigational new drug (pre-IND) development makes the volume unique. Unlike before, the incorporation of several simplified protocols, breeding methodologies, handling and assessment procedures to study drug intervention makes this book a must read. Animal Models in Cancer Drug Discovery is a valuable resource for basic and translational cancer researchers, drug discovery researchers, contract research organizations, and knowledge seekers at all levels in the biomedical field.
Patient Derived Tumor Xenograft Models: Promise, Potential and Practice offers guidance on how to conduct PDX modeling and trials, including how to know when these models are appropriate for use, and how the data should be interpreted through the selection of immunodeficient strains. In addition, proper methodologies suitable for growing different type of tumors, acquisition of pathology, genomic and other data about the tumor, potential pitfalls, and confounding background pathologies that occur in these models are also included, as is a discussion of the facilities and infrastructure required to operate a PDX laboratory. - Offers guidance on data interpretation and regulatory aspects - Provides useful techniques and strategies for working with PDX models - Includes practical tools and potential pitfalls for best practices - Compiles all knowledge of PDX models research in one resource - Presents the results of first ever global survey on standards of PDX development and usage in academia and industry
The way a cell undergoes malignant transformation should meet their capacity of surviving in the microenvironment of the organ where the cancer will develop. Metabolic adaptation is for sure one of the criteria that must be accomplished, driven by metabolic plasticity that allows the adaptation of cancer cells to the availability of energy and biomass sources that will sustain cell survival and proliferation. Each human organ has a particular microenvironment which depends on several cell types and in some cases also on symbiotic microorganisms. These biological partners are constantly sharing organic compounds and signaling molecules that will control mitogenesis, cell death and differentiation, accounting for the organ's function. Nevertheless, cancer cells are capable of taking advantage of this metabolic and signaling microenvironmental dynamics. In this book, we intend to present the different components of the microenvironment driving the metabolic fitness of cancer cells. The metabolic changes required for establishing a tumor in a given microenvironment and how these metabolic changes limit the response to drugs will generally be the major items addressed. It is important to mention not only aspects of the microenvironment that stimulate metabolic changes and that select better adapted tumor cells, but also how this regulation of cell plasticity is made. Thus, the signaling pathways that orchestrate and are orchestrated throughout this panoply of metabolic rearrangements will also be addressed in this book. The subjects will be presented from the conceptual point of view of the cross-cancer mechanisms and also particularizing some models that can be examples and enlightening within the different areas.
This open access book presents recent advances in the pure sciences that are of significance in the quest for alternatives to the use of animals in research and describes a variety of practical applications of the three key guiding principles for the more ethical use of animals in experiments – replacement, reduction, and refinement, collectively known as the 3Rs. Important examples from across the world of implementation of the 3Rs in the testing of cosmetics, chemicals, pesticides, and biologics, including vaccines, are described, with additional information on relevant regulations. The coverage also encompasses emerging approaches to alternative tests and the 3Rs. The book is based on the most informative contributions delivered at the Asian Congress 2016 on Alternatives and Animal Use in the Life Sciences. It will be of value for those working in R&D, for graduate students, and for educators in various fields, including the pharmaceutical and cosmetic sciences, pharmacology, toxicology, and animal welfare. The free, open access distribution of Alternatives to Animal Testing is enabled by the Creative Commons Attribution license in International version 4: CC BY 4.0.
Because of its marked capacity to regenerate and the ability of chemical carcinogens and viruses to ready transform hepatocytes, the liver has been used extensively as a model for investigating the molecular mechanisms of cellular proliferation and carcinogenesis. Recently, striking advances have occured in the understanding of hepatocyte growth regulation and the manner in which chemical agents and viruses alter these normal growth regulatory pathways in liver carcinogenesis. This explosion of information has occured in a multitude of researh disciplines. This book brings together current findings in a coherent manner, from a molecular point of view. Three sections cover in detail the areas of liver regeneration, liver carcinogenesis, and liver tumor therapy. The contributors are pioneers and leaders in this field.* Logical organization of material in three detailed and comprehensive sections: liver regeneration, liver carcinogenesis, and liver tumor treatment* Contributors are pioneers and leaders in the field* There are currently no books on this subject on the market* Research focus is at the molecular level
Origins of Inbred Mice documents the proceedings of a symposium on the state of knowledge on inbred mice held in Bethesda, Maryland, in 1978. The book is organized into seven parts. Part I provides introductory remarks on the history of the development of inbred mice. Part II contains papers that examine mutations of inbred strains of mice. Part III contains studies dealing with viruses that affect inbred mice, including those that cause leukemia and mammary tumors. Part IV examines histocompatibility genes and their antigens; cell surface antigens of mouse leukemia; the characteristics of genes of the Tla region of the mouse; and the use of recombinant inbred strains in gene mapping. Part V presents studies on differences among sublines of inbred mouse strains. The papers in Part VI focus on wild mice, covering their classification and biochemical polymorphisms. Finally, Part VIII discusses the viruses, T locus, and histocompatibility antigens of wild mice.
Scientists from both academia and industry in many countries have closely cooperated to arrive at a consensus on the descriptions of all the types of tumour and preneoplastic lesions encountered in laboratory mice. The series of fascicles should provide information and guidelines especially adapted for international use in practical toxicologic pathology. Images showing the typical appearance of the discussed lesions and references to the most recently published papers complete the information presented here.