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Research Description:
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, pharmacodynamics and efficacy. The laboratory is also interested in non-invasively measuring compounds with absorbance spectra in the long visible range. Specific studies include the pharmacokinetics 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 pancreatic cancer xenografts. The pharmacokinetics and efficacy of tubulin interactive agents including docetaxel, paclitaxel and 6-epi-dictyostatin are also under investigation. 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 use 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. Other agents investigated include a wide range of potential cancer chemotherapeutics including DB-67, CKD-602, 2,2-dimethylbutyrate, DA-3003-1, Zebularine, 17-allyl aminogeldanamycin and 17-dimethylamino-geldanamycin.
Education:
B.S. (Chemistry), University of Michigan, Ann Arbor, MI, 1969.
M.S. (Pharmacology), Michigan State University, East Lansing, MI, 1971.
Ph.D. (Pharmacology), Cornell University Medical College, New York, NY, 1980.
Important Publications:
- Beumer JH, JL Eiseman, J Gilbert, JL Holleran, A Yellow-Duke, D Clausen, D D'Argenio, M Ames P Hershberger, RA Parise, L Bai, JA Covey and ML Egorin. Plasma pharmacokinetics and oral bioavailabiity of the 3,4,5,6-tetrahydrouridine (THU) prodrug, triacetyl-THU (taTHU) in mice. Cancer Chemother Pharmacol, in press, 2010
- Holleran JL, RA Parise, AE Yellow-Duke, MJ Egorin, JL Eiseman, JM Covey and JH Beumer. Liquid chromatography-tandem mass spectrometric assay for the quantitation in human plasma of the novel indenoisoquinoline topoisomerase I inhibitors, NSC 743400 and NSC 725776. J Pharm Biomed Anal 52:714-720, 2010
- Bai L, J Guo, FA Bontempo and JL Eiseman. The relationship of phthalocyanine 4 (Pc 4) concentrations measured non-invasively to outcome of Pc 4 photodynamic therapy in mice. Photochemistry and Photobiology 85:1011-1019, 2009
- Guo P, RA Parise, E Joseph, MJ Egorin, EK Prochownik and JL Eiseman. Efficacy, pharmacokinetics, tissue distribution, and metabolism of the Myc-Max disruptor, 10058-F4 [Z,E]-[4-ethylbenzylidine]-2-thioxothiazolidin-4-one, in mice. Cancer Chemother Pharmacol 63:615-625, 2009
- Beumer JH, JL Eiseman, RA Parise, JM Covey and MJ Egorin. Modulation of gemcitabine (2',2'-difluoro-2'-deoxycytidine) pharmacokinetics, metabolism, and bioavailability in mice by 3,4,5,6-tetrahydrouridine. Clin Cancer Res 14:3529-3535, 2008
- Eiseman JL, L Bai, W-H Jung, J Moura-Letts, BW Day and DP Curran. Improved synthesis of 6-epi-dictyostatin and antitumor efficacy in mice bearing MDA-MB231 human breast cancer xenografts. J Med Chem 51:6650-6653, 2008
- Kanick SC, JL Eiseman and RS Parker. Pharmacokinetic modeling of motexafin gadolinium disposition in mouse tissues using optical pharmacokinetic system measurements. Photodiagnosis and Photodynamic Therapy 5:276-284, 2008
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