Research in the Eiseman laboratory is directed at the preclinical evaluation of potential anti-cancer agents. Studies include the determination of the maximum tolerated dose, pharmacokinetics, metabolism, pharmacodynamics and efficacy. The laboratory is also interested in non-invasively measuring compounds with absorbance spectra in the long visible range. Dr. Eiseman’s laboratory is one of 5 contractors with the NCI to conduct preclinical pharmacology studies of anticancer and anti AIDs agents.
Specific studies include the pharmacokinetics, metabolism and efficacy of the pyrimidine compounds, fluorodeoxycytidine (FdCyd) and gemcitabine (dFdCyd) in combination with a cytidine deaminase inhibitor, tetrahydrouridine in CD2F1 mice and SCID mice with human cancer xenografts, toxicology studies in monkeys and supporting the Phase I and Phase II clinical trials of these compounds. . Additional studies are also examining a new class of topoisomerase I inhibitors currently in clinical trials at the NCI.
The pharmacokinetics and efficacy of protein kinase D inhibitors are being evaluated in collaboration with Drs. Jane Wang and Peter Wipf. C-Myc-Max inhibitors are being evaluated in collaboration with Drs Ed Prochownik and John Lazo. Studies with docetaxel have examined the interaction with 9-nitrocamptothecin in an ovarian cancer xenograft (SK-OV3) and a physiological based pharmacokinetic model was developed to describe the disposition of docetaxel. This model will be evaluated for its usefulness in predicting patient docetaxel pharmacokinetics.
Dr. Eiseman is interested in understanding the mechanisms involved during photodynamic therapy with Pc 4 and other phototherapeutic agents and uses elastic scattering spectrometry to measure changes in drug concentrations and hemoglobin saturation during and following photodynamic therapy. For these studies, we measure the concentrations of the drug and hemoglobin non-invasively as well as through destructive methods such as HPLC and LC/MS-MS. We are interested in novel delivery systems to direct the Pc 4 to the tumor
Other agents investigated include a wide range of potential cancer chemotherapeutics including Benzaldehyde Dimethane Sulfonate, DB-67, CKD-602, 2,2-dimethylbutyrate, DA-3003-1, Zebularine, 17-allyl aminogeldanamycin and 17-dimethylamino-geldanamycin.
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