Search

Since 1990, the National Cancer Institute (NCI) has screened more than 60,000 compounds against a panel of 60 human cancer cell lines. The 50-percent growth-inhibitory concentration (GI50) for any single cell line is simply an index of cytotoxicity or cytostasis, but the patterns of 60 such GI50 values encode unexpectedly rich, detailed information on mechanisms of drug action and drug resistance. Each compound's pattern is like a fingerprint, essentially unique among the many billions of distinguishable possibilities. These activity patterns are being used in conjunction with molecular structural features of the tested agents to explore the NCI's database of more than 460,000 compounds, and they are providing insight into potential target molecules and modulators of activity in the 60 cell lines. For example, the information is being used to search for candidate anticancer drugs that are not dependent on intact p53 suppressor gene function for their activity. It remains to be seen how effective this information-intensive strategy will be at generating new clinically active agents.

Estimates of ventilatory clearance are usually made by inspecting xenon washout images. Quantitative computer procedures have been described that produce regional clearance rates, yet their accuracy is not well established. We define a mathematical model for scintigraphic ventilation data based on 96 clinical studies, and with this model we test the accuracy of two procedures used to estimate ventilatory clearance. The least-squares curve-fitting technique for both washin and washout data has the same accuracy as a modified Stewart-Hamilton method (A/H) that uses washout data alone. Both procedures demonstrate relative errors of less than 5% and coefficients of variation of 10-20% when regions with equilibrium count rates of 3 cps and clearance times between 10 and 90 sec are examined. Because the A/H procedure is preferred for its simplicity and speed, we analyze two of its main sources of error: early washin/washout termination and background activity. To measure regional ventilation by the A/H procedure, we recommend: (a) washin and washout periods at least three times the largest clearance time of clinical interest; b) a regional equilibrium count rate of at least 3cps; and c) a 25- to 50-sec average of the equilibrium count rate.