Comparative and Veterinary Specialty Section

Description: Hormones secreted by cells of the endocrine system have diverse effects throughout the body. Exposure to xenobiotic compounds can result in profound changes to the endocrine organs and/or their target cells. Significant species differences exist in the structure and function of endocrine and reproductive organs making interpretation of test results and extrapolation from animal models to humans more challenging. In addition to the numerous anatomical and physiological differences, there are also species variations in metabolism and response to toxicants. It is the goal of these presentations to give an overview of the structure, function, regulation, and toxic responses of selected endocrine and reproductive organs. In addition, the speakers will discuss the hormonal assays and other mechanistic approaches necessary to make species comparisons, and to extrapolate the findings from animals to humans. Each presentation will briefly describe important species differences with regard to anatomy, endocrine physiology, and response to different classes of xenobiotic chemicals by selected endocrine and reproductive organs such as the thyroid (follicular cells), ovary, and testis (Leydig cells). One presentation will focus on the principles and pitfalls of hormonal measurements in laboratory animals considering advantages/disadvantages of different methods, species specificity of certain assays, most appropriate sampling times, and other useful items to consider in future protocol development. Following completion of this workshop, attendees should have a more complete understanding of the comparative endocrinology and toxicology of selected endocrine and reproductive organs in laboratory animals.

Targeted Therapeutic Approach to Anti-Cancer Drug Development- Chairs: Vijayapal Reddy and Myrtle Davis

Description: Over the past decade, a range of targeted anti-cancer drugs have been developed that are designed to interfere with one or more of the many molecular mechanisms that drive tumor growth. The molecularly-targeted approach to the development of these new anti-cancer drugs has created a false impression that these newer drugs, unlike earlier cytotoxic anti-cancer drugs, will be non-toxic. Cytotoxic drugs are typically administered in short courses of maximal doses (MTD). This is not necessarily appropriate for targeted therapies, which can require long-term therapy and for which it is often difficult to determine the biologically most effective dosage (BED). This course will focus on different aspects of regulatory, preclinical, and clinical targeted anti-cancer drug development. The first speaker will focus on tumor cell biology and the respective cell signaling pathways that hold promise for targeted anti-cancer therapy. The second speaker will present differences in preclinical development philosophy between cytotoxic and targeted anti-cancer drugs. The third speaker will discuss specific examples of preclinical development of targeted biotherapeutics. The fourth speaker will discuss biomarkers as endpoints of clinical efficacy and safety assessment. The final speaker will focus on regulatory considerations of preclinical development of targeted therapies, highlighting differences between cytotoxic and targeted therapies. This advanced course in drug development is targeted to government, biotechnology and pharmaceutical toxicologists as well as general toxicologists with an interest in cancer chemotherapy.

Neuropathology for the Toxicologist- Chair: David Dorman

Description: This course is designed to provide a basic overview of rodent neuropathology. The course will start off with a review of the normal anatomy and histology of the adult nervous system. This overview will also discuss the ways in which neuropathology and functional assays of motor activity and other behaviors relate to one another. The second lecture relates to tissue handling techniques and basic approaches in neuropathology. This topic is critically important since the ability to detect chemical-induced neuropathology requires proper tissue fixation and processing. Although the second lecture will largely focus on rodent tissues, the approaches and methods to be discussed can be easily adapted to other species. The course will then transition into two presentations focused on common lesions induced by model neurotoxicants. One presentation will focus on central nervous system effects while the latter lecture will address peripheral neuropathies. Our final presentation will discuss morphometric approaches in neuropathology including a discussion of the use of magnetic resonance imaging methods in neurotoxicologic pathology. Participants in this course will gain a greatly improved appreciation of basic neuropathology and applications to toxicology.