Katherine Nelson

The effects of acute administration of cytotoxic anticancer agents on the capacity for subsequent hormonal responses in the mouse uterus.

The mouse uterus has been used as a model system with which to examine the interaction of anticancer agents with steroid hormone receptors and to evaluate the effect of a single exposure to a cytotoxic anticancer agent on the subsequent elicitation of the uterotrophic response to estradiol. The uterotrophic response was interpreted in terms of the induction of progesterone receptors, uterine weight gain and increased uterine DNA content. Evaluation of 34 cytotoxic agents selected for this study provided little evidence to substantiate the interaction of these agents with estrogen or progesterone receptors. Although prior treatment with certain cytotoxic agents partially inhibited the subsequent responses to estradiol, some capacity to respond to estradiol was always retained. The majority of cytotoxic agents had little impact on the capacity to respond to estradiol. Thus, in these studies where high sublethal concentrations of cytotoxic agents were administered prior to estradiol, there was no indication that the mechanisms regulating subsequent hormonal responses were compromised.

Antiestrogen Resistance in Human Breast Cancer

Breast cancer will be diagnosed in over 185,000 women in 1996 and will claim more than 44,000 lives (Parker et al, 1996). Antiestrogen (AE) therapy will widely be assigned to a large number of these individuals who are estrogen receptor-positive. Unfortunately, many of these women will eventually become resistant to AE therapy with little prospect for additional effective therapy. It is clear that approaches are needed that reintroduce tumor inhibition in AE-resistant breast cancer cells. Since AE resistance is frequently associated with disease that is refractory to chemotherapy, genes that moderate the action of chemotherapeutic agents also may be affected by the onset of AE resistance. This chapter presents a current overview of AE resistance and describes some of our laboratory’s efforts to restore growth inhibition in AE-resistant breast cancer cells.

Visicalc™ and Visiplot™ software routines and the analysis of data routinely encountered in steroid biochemistry

The use of VisiCalc and VisiPlot software routines for performing calculations and graphing of data commonly encountered in steroid biochemistry is described. These software routines have utility and are relatively easy to use, requiring little or no programming experience. Use of these routines is demonstrated in terms of data processing associated with chromatography of receptor preparations and equilibrium binding analyses. The execution of these software routines is rapid and can result in a considerable savings of time and personnel. These and other generically similar software routines should have the greatest utility in laboratories where the experimental design is subject to on-going change.