Evaluation of arylmethylaminopropanediols by a novel in vitro pharmacodynamic assay: correlation with antitumor activity in vivo

The pharmacodynamics of a new series of antitumor DNA intercalators, known as arylmethylaminopropanediols (AMAPs), has been evaluated in vitro against adherent (MCF-7 human breast cancer) and nonadherent (P388 murine leukemia) cell lines. Previous work had shown that the in vitro antitumor activity of the model AMAP crisnatol was a function of exposure (Cn x T), rather than concentration alone. A unique exposure parameter, the minimum C x T, was proposed as an end point for antitumor activity in cell culture. Comparison of crisnatol to several established agents by the minimum C x T versus the standard concentration producing 10% survival indicated that these end points were not equivalent. The current work examined the validity of the pharmacodynamic approach using AMAP isomers from three different ring systems that were known to exhibit a spectrum of activity against the P388 tumor in vivo. The results indicated that antiproliferative, but not cytotoxic, activity of AMAPs in the pharmacodynamic assay correlated with their differential activity in vivo, expressed as percentage of increase in life span. In contrast, the concentration producing 10% survival either at 1 h or after continuous exposure did not show a similar correlation. The pharmacodynamic assay also revealed that certain AMAPs, while equipotent by concentration alone, required significantly less time and therefore less overall exposure for efficacy. Finally, the activity of AMAP isomers in P388 cells differed from that in MCF-7 cells, which may indicate AMAP selectivity for certain tumor types. Since AMAP action was a function of exposure, drug effects on cellular targets could likewise depend on exposure rather than concentration. These findings emphasize the importance of relating drug mechanisms to the pharmacodynamics of anticancer agents.     

Efficacy of selected complementary and alternative medicine interventions for chronic pain

Complementary and alternative medicine (CAM) is a group of diverse medical and healthcare systems, therapies, and products that are not presently considered part of conventional medicine. This article provides an up-to-date review of the efficacy of selected CAM modalities in the management of chronic pain. Findings are presented according to the classification system developed by the National Institutes of Health National Center for Complementary and Alternative Medicine (formerly Office of Alternative Medicine) and are grouped into four domains: biologically based medicine, energy medicine, manipulative and body-based medicine, and mind-body medicine. Homeopathy and acupuncture are discussed separately as "whole or professionalized CAM practices." Based on the guidelines of the Clinical Psychology Division of the American Psychological Association, findings indicate that some CAM modalities have a solid track record of efficacy, whereas others are promising but require additional research. The article concludes with recommendations to pain practitioners.