Catálogo de publicaciones - revistas

<jats:p> Chromosomal translocations in the human acute leukemias rearrange the regulatory and coding regions of a variety of transcription factor genes. The resultant protein products can interfere with regulatory cascades that control the growth, differentiation, and survival of normal blood cell precursors. Support for this interpretation comes from the results of gene manipulation studies in mice, as well as the sequence homology of oncogenic transcription factors with proteins known to regulate embryonic development in primitive organisms, including the nematode <jats:italic>Caenorhabditis elegans</jats:italic> and the fruit fly <jats:italic>Drosophila melanogaster</jats:italic> . Many of these genetic alterations have important prognostic implications that can guide the selection of therapy. The insights gained from studies of translocation-generated oncogenes and their protein products should hasten the development of highly specific, and hence less toxic, forms of leukemia therapy. </jats:p>

<jats:p>The discovery of anticancer drugs is now driven by the numerous molecular alterations identified in tumor cells over the past decade. To exploit these alterations, it is necessary to understand how they define a molecular context that allows increased sensitivity to particular compounds. Traditional genetic approaches together with the new wealth of genomic information for both human and model organisms open up strategies by which drugs can be profiled for their ability to selectively kill cells in a molecular context that matches those found in tumors. Similarly, it may be possible to identify and validate new targets for drugs that would selectively kill tumor cells with a particular molecular context. This article outlines some of the ways that yeast genetics can be used to streamline anticancer drug discovery.</jats:p>

<jats:p>Acting in concert with individual susceptibility, environmental factors such as smoking, diet, and pollutants play a role in most human cancer. However, new molecular evidence indicates that specific groups—characterized by predisposing genetic traits or ethnicity, the very young, and women—may have heightened risk from certain exposures. This is illustrated by molecular epidemiologic studies of environmental carcinogens such as polycyclic aromatic hydrocarbons and aromatic amines. Individual genetic screening for rare high-risk traits or for more common, low-penetrant susceptibility genes is problematic and not routinely recommended. However, knowledge of the full spectrum of both genetic and acquired susceptibility in the population will be instrumental in developing health and regulatory policies that increase protection of the more susceptible groups from risks of environmental carcinogens. This will necessitate revision of current risk assessment methodologies to explicitly account for individual variation in susceptibility to environmental carcinogens.</jats:p>

<jats:p> Chemoprevention is the use of pharmacologic or natural agents that inhibit the development of invasive cancer either by blocking the DNA damage that initiates carcinogenesis or by arresting or reversing the progression of premalignant cells in which such damage has already occurred. Recent advances in our understanding of the mechanisms of carcinogenesis have led to the synthesis of new drugs that can inhibit tumor development in experimental animals by selective action on specific molecular targets, such as the estrogen, androgen, and retinoid receptors or inducible cyclooxygenase. Several of these agents (including tamoxifen, 13- <jats:italic>cis</jats:italic> -retinoic acid, retinyl palmitate, and an acyclic retinoid) are clinically effective in preventing the development of cancer, particularly in patients who are at high risk for developing second primary tumors after surgical removal of the initial tumor. </jats:p>

<jats:p> <jats:bold>Beginnings Count.</jats:bold> The Technological Imperative in American Health Care. DAVID J. ROTHMAN. Oxford University Press, New York, 1997. xiv, 189 pp. $24.95 or §18.95. ISBN 0-19-511118-4. A Twentieth Century Fund Book. </jats:p>

<jats:p> <jats:bold>Patterns and Processes of Vertebrate Evolution.</jats:bold> ROBERT L. CARROLL. Cambridge University Press, New York, 1997. xvi, 448 pp., illus. $85 or £70, ISBN 0-521-47232-6; paper, $39.95 or £24.95, ISBN 0-521-47809-x. Cambridge Paleobiology, 2. </jats:p>