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D T Andrews

Publications and source records attributed to D T Andrews.

4 recordsLinked to original sources
PubMed2000

A gene expression database for the molecular pharmacology of cancer.

We used cDNA microarrays to assess gene expression profiles in 60 human cancer cell lines used in a drug discovery screen by the National Cancer Institute. Using these data, we linked bioinformatics and chemoinformatics by correlating gene expression and drug activity patterns in the NCI60 lines. Clustering the cell lines on the basis of gene expression yielded relationships very different from those obtained by clustering the cell lines on the basis of their response to drugs. Gene-drug relationships for the clinical agents 5-fluorouracil and L-asparaginase exemplify how variations in the transcript levels of particular genes relate to mechanisms of drug sensitivity and resistance. This is the first study to integrate large databases on gene expression and molecular pharmacology.

Antineoplastic Agents↗
PubMed1997

The arterial blood propofol concentration preventing movement in 50% of healthy women after skin incision.

To target appropriate drug concentrations and to facilitate comparisons between drugs, the potency of propofol must be firmly established. We therefore determined the arterial blood propofol concentration preventing movement in 50% of patients after skin incision and the ability of arterial blood pressure and heart rate to predict movement after incision. Fifteen healthy women scheduled for breast surgery were randomly assigned to computer-targeted propofol blood concentrations. No other drugs were administered. Fifteen minutes after starting the propofol infusion, a 5-cm skin incision was made. Patients were observed for gross purposeful movement for 1 min. Arterial blood was sampled for propofol to confirm steady-state blood concentrations. Arterial blood pressure and heart rate were measured noninvasively. Logistic regression was used to calculate the propofol blood concentrations and arterial blood pressures at which 50% and 95% of patients did not move after skin incision (CP50 and CP95, MABP50 and MABP95, respectively). The CP50 and CP95 values for propofol were 14.3 +/- 1.6 microg/mL (mean +/- SE) and 20.6 microg/mL, respectively. The MABP50 and MABP95 values were 63 +/- 4 mm Hg and 43 mm Hg, respectively. Heart rate did not differ significantly in patients who moved and who did not move. Propofol blood concentrations required to prevent movement in most patients resulted in significant arterial hypotension.

Adult↗
PubMedDate not supplied

Mining and visualizing large anticancer drug discovery databases.

In order to find more effective anticancer drugs, the U.S. National Cancer Institute (NCI) screens a large number of compounds in vitro against 60 human cancer cell lines from different organs of origin. About 70,000 compounds have been tested in the program since 1990, and each tested compound can be characterized by a vector (i.e., "fingerprint") of 60 anticancer activity, or -[log(GI50)], values. GI50 is the concentration required to inhibit cell growth by 50% compared with untreated controls. Although cell growth inhibitory activity for a single cell line is not very informative, activity patterns across the 60 cell lines can provide incisive information on the mechanisms of action of screened compounds and also on molecular targets and modulators of activity within the cancer cells. Various statistical and artificial intelligence methods, including principal component analysis, hierarchical cluster analysis, stepwise linear regression, multidimensional scaling, neural network modeling, and genetic function approximation, among others, can be used to analyze this large activity database. Mining the database can provide useful information: (a) for the development of anticancer drugs; (b) for a better understanding of the molecular pharmacology of cancer; and (c) for improvement of the drug discovery process.

Algorithms↗