apy agent. The low-dose pre-treatment appeared to temporarily turn off the gene that produces P-glycoprotein, producing a "window" of time during which there was an increase in the sensitivity of the cells to the killing effect of the second drug. The researchers achieved similar results by priming cells with three other cross-linking drugs.

"Opening the window takes about 24 hours, and it stays open for another 72 hours -- and that's the period when the second drug is most effective," says Hamilton. The researchers report similar results in drug-resistant cells derived from breast, colon, liver, leukemia and brain tumors. Preliminary results from animal and human studies, using paclitaxel (Taxol), doxorubicin and mitomycin, are consistent with these findings.

The results suggest that a similar pretreatment regimen may increase the efficacy of cancer chemotherapy in patients. Sequential use of chemotherapeutic agents would minimize drug interactions as well as side effects.

The researchers are now doing animal studies to determine the most effective combination of drugs, and human clinical trials to determine the effectiveness of this approach in various natural cancers.

The Dartmouth team includes Michael Ihnat, Jean Lariviere, Amy Warren, Nicole La Ronde, Johanna Blaxall, Karana Pierre and Bruce Turpie. The work was supported by grants from the National Cancer Institute, the International Life Sciences Institute Inc., the American Cancer Society and the Cotton Cancer Center.

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Contact: Nancy Serrell
nancy.serrell@dartmouth.edu
603/650-3661
Dartmouth Medical School
13-Aug-1997


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