Since the discovery of p53 as a tumor suppressor, numerous methods have evolved to reveal the unique structural features and biochemical functions of this protein. Several unique properties of p53 posed a challenge to understa- ing its normal function in the initial phase of its research. The low levels of p53 in normal cells, its stabilization under situations of genotoxic stress, induction of growth arrest, and apoptosis with stabilization of the protein, obstructed the visibility of its normal, unmutated function. The property of p53 that can sense a promoter and transactivate or inhibit is still not well understood. It is still not known whether it is the absence of the protein that causes tumorigenesis, or if its mutants have a dominant role in inducing cancer. p53 Protocols comprises eighteen chapters for the study of the diverse properties of p53 and related proteins. The methods included are invaluable for delineating the function of other proteins that may function as tumor suppr- sors or growth suppressors. The chapters are not presented in any schematic order, for the importance and diversity of the functions of p53 make it imp- sible to organize them suitably. We have made a sincere effort to collect the methods most useful to those investigators working on tumor suppressors or growth suppressors. The purpose of p53 Protocols is not only to provide investigators with methods to analyze similar biochemical functions, but also to familiarize them with the associated problems that arose during the course of investigations.

Decades of research on the tumor suppressor p53 have revealed that it plays a significant role as a "guardian of the genome," protecting cells against genotoxic stress. In recent years, p53 research has begun to move into the clinic in attempts to understand how p53 is frequently inactivated in-and sometimes even promotes-human cancer. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine covers the rapid progress that has recently been made in basic and clinical research on p53. The contributors review new observations about its basic biology, providing updates on the functions of its isoforms and domains, the myriad stresses and signals that trigger its activation or repression, and its downstream effects on genome stability and the cell cycle that enforce tumor suppression in different cell and tissue types. They also discuss how p53 dysfunction contributes to cancer, exploring the various inherited and somatic mutations in the human TP53 gene, the impact of mutant p53 proteins on tumorigenesis, and the prognostic value and clinical outcomes of these mutations. Drugs that are being developed to respond to tumors harboring aberrant p53 are also described. This book is therefore essential reading for all cancer biologists, cell and molecular biologists, and pharmacologists concerned with the treatment of this disease.

This volume offers a comprehensive review of the functions of the p53 family. The contributors examine the normal roles of these transcription factors, their evolution, the regulatory mechanisms that control p53 activity, and the part played by p53 mutations in tumorigenesis.

Simian virus 40 gained notoriety in the 1960s because it was found to be a contaminant of polio and adenovirus vaccines that had been administered to millions of healthy individuals worldwide. The public health implications of this revelation provided the initial impetus for an in-depth study of SV40 biology. Later work showed that SV40 DNA sequences as well as infectious virus are in fact found in human tumors and may have contributed to oncog- esis. It also turned out that SV40 uses mostly cellular machinery to carry out many steps in viral infection, which makes it a powerful probe for examining many fundamental questions in eukaryotic molecular biology. SV40 Pro- cols consolidates a number of well-tested step-by-step techniques in one v- ume; experts with hands-on experience in particular methods give detailed accounts of their optimized experimental protocols, so that the beginner, as well as more experienced researchers, may readily overcome problems of ambiguity often present in the literature. As with other DNA tumor viruses, the response of cultured cells to SV40 infection depends upon the species being infected. Monkey cells s- port virus production, which leads to their death, whereas rodent cells p- duce only the early proteins and acquire a transformed phenotype. Thus, SV40 Protocols is organized in two sections. The first relates to assays of the lytic cycle of the virus, and the second deals with transformation.

A collection of cutting-edge techniques for analyzing genotoxic exposure and detecting the resulting biological effects-including endogenous metabolites-up to and including the development of cancer. The authors emphasize analytical methods that can be specifically applied to human populations and patients. Among the applications detailed are the analysis of interactions between such cellular macromolecules as DNA and proteins and chemical and physical agents, the assessment of medically relevant toxicity, and the characterization of genetic alterations induced in transgenic animals by in vivo systems. There are also methods for the analysis of genotoxic exposure during gene expression, of cytotoxicity caused by the induction of apoptosis, of genetic alterations in reporter genes and oncogenes, early (premalignant) detection of altered oncogenes, and of individual variation in biotransformation and DNA repair capacity.

The daily analysis of whole-body MRI datasets uncovers many incidental findings, which are discussed by an interdisciplinary advisory board of physicians. This book provides a systematic overview of these incidental findings with the aid of approximately 240 high-quality images. The radiologists involved in the project have written chapters on each organ system, presenting a structured compilation of the most common findings, their morphologic appearances on whole-body MRI, and guidance on their clinical management. Chapters on technical and ethical issues are also included. It is hoped that this book will assist other diagnosticians in deciding how to handle the most common incidental findings encountered when performing whole-body MRI.

This is the first in a series of volumes concerning the properties of the eukaryotic nucleus. Contributions from several of the most active laboratories are brought together to present a focused overview of a selected aspect of nuclear structure and function.