Validation of Toxicogenomic Technologies

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Toxicogenomics has been described as a discipline combining ex-pertise in toxicology, genetics, molecular biology, and environmental health to elucidate the response of living organisms to stressful environ-ments. It includes the study of how genomes respond to toxicant expo-sures and how genotype affects responses to toxicant exposures. As the technologies for monitoring these responses rapidly develop, it is critical that scientists and regulators are confident that the technologies are reliable and reproducible and that the data analyses have been validated. To discuss these issues in a public forum, the Committee on the Validation of Toxicogenomic Technologies designed a workshop to consider the current practice and advances in the validation of toxicogenomic tech-nologies. The workshop focused on the technical aspects of validation, recognizing it as a prerequisite for considering other important issues, such as biological validation (e.g., validating the use of microarray “sig-natures” to describe a toxic effect).

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Target Validation in Drug Discovery

This work presents a comprehensive contemporary framework for approaching target validation in drug discovery. It begins with a detailed description of new enabling technologies, including aptamers, RNA interference, functional genomics, and proteomics. The next section looks at biologic drug development with in-depth discussion of lessonslearned from such well-known cases as Erbitux, Herceptin, and Avastin. Additional targets known as "second generation" drugs, which can be identified when disease pathways are validated by biologics, present new possible small molecule therapeutics and serve as the focus of the final section of the book

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Animal Models in Toxicology, Second Edition

Animal Models in Toxicology, Second Edition 

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Animal Models in Toxicology, Second Edition

By Shayne C. Gad, Gad Consulting Services, Cary, North Carolina, USA

Book Specifications

• Available to Purchase
• Published: Oct-06
• ISBN: 9780824754075
• Second Edition
• 952 pages
• Format: Hardcover
• Size: 7" x 10"
• 33 Black and White Illustrations

Quick Overview

Reflecting a decade's worth of changes, this Second Edition is a practical guide to the common statistical problems encountered in toxicology and the methodologies that are available to solve them.

Reflecting a decade's worth of changes, this Second Edition is a practical guide to the common statistical problems encountered in toxicology and the methodologies that are available to solve them.
The book presents a historical review of the use of animal models used in toxicology and an overview of broad considerations of metabolism and its relevance.
Chapters covering the eight major species used in toxicology and experimental biology form the core of the book. With contributions from experts in toxicology, toxicological pathology, and species-specific metabolism, each of these chapters provide an excellent introductory course along with guidance to the literature for more detailed understanding.

Features:

• provides tables of normative physiology, pathology, reproductive, clinical laboratory, and metabolism data
• presents detailed discussions of husbandry, major diseases, and handling for the major species used in toxicology and experimental biology
• contains detailed descriptions and illustrations for dosing, blood collection, and other procedures
• reviews current laws and regulations governing animal care and use in major countries
• includes extensive appendices of acronyms, regulatory and scientific Web sites, animal suppliers, and a lexicon of terms used in describing clinical signs

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Tumor Models in Cancer Research

Progress in a given field is often dependent upon the development of appropriate, accurate models. In modern times, cancer research has been engaged in a focused search for such models for more than 50 years. The foremost problem in developing such models is that cancer is many, many diseases arising from nearly every tissue and metastasizing too many.

A major breakthrough for models in cancer research was the development of transplantable rodent tumors. Many of the early tumor lines were carcinogen-induced, but others arose naturally in elderly animals from inbred strains of mice. These syngeneic tumors grown in the inbred host of origin allowed reproducible tumor growth and reproducible response to anticancer agents to be achieved. These tumor lines also frequently allowed analysis of tumor metastasis in the host.

The mutual needs for as large an array as possible of tumor types and the expansion of true inbred strains of mice to carry these tumors led to the identification of mutant mice with characteristics of deficient immunity suitable for the growth of human tumors as xenografts. The most frequently used of these mutant mouse strains are nude mice and SCID mice. Human tumor xenograft models were established from the many human tumor cell lines developed in the 1970s and 1980s and from fresh tumor explants. Since techniques for genetic manipulation have become more routine, animals expressing “oncogenes” or missing “tumor suppressor” genes have been developed, allowing a new level of understanding of the process of malignancy and new models for testing anticancer agent efficacy. Through the use of these techniques for some diseases and targets, it has been possible to establish specific animal models.

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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.

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