| |
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:
- Eiseman JL, J Guo, RK Ramanathan, CP Belani, DB Solit, HI Scher, SP Ivy, EG Zuhowski and MJ Egorin. Evaluation of plasma insulin-like growth factor binding protein 2 (IGFBP-2) and Her-2 extracellular domain (Her-2 ECD) as biomarkers for 17-allylamino-17-demethoxygeldanamycin (17-AAG) treatment of adult patients with advanced solid tumors. Clinical Cancer Research 13:2121-2127, 2007
- Guo J, RA Parise, E Joseph, J Lan, S-S Pan, B Joo, MJ Egorin, P Wipf, JS Laso and JL Eiseman. Pharmacology and antitumor activity of a quinolinedione Cdc25 phosphatase inhibitor, DA-3003-1 (NSC 663284). Anticancer Research 27:3067-3073, 2007
- Kanick SC, JL Eiseman, E Joseph, J Guo and RS Parker. Nonivasive and nondestructive optical spectroscopic measurements of motexafin gadolinium in mouse tissues: Comparison to high-performance liquid chromatography. Journal of Photochemistry and Photobiology B: Biology 88:90-104, 2007
- Zamboni WC, S Strychor, E Joseph, DR Walsh, RA Parise, ME Tonda, NY Yu, C Engber, JL Eiseman. Plasma, tumor, and tissue disposition of STEALTH liposomal CKD-602 (S-CKD602) and non-liposomal CKD-602 in mice bearing A375 human melanoma xenografts. Clinical Cancer Research 13:7217-7223, 2007
- Zamboni WC, S Strychor, E Joseph, R Parise, MJ Egorin and JL Eiseman. Antitumor response and pharmacokinetic study of docetaxel in combination with 9-nitrocamptothecin in mice bearing SKOV3 human ovarian xenografts. Cancer Chemother Pharmacol, in press, 2007
- Beumer JH, E Joseph, MJ Egorin, RS Parker, DZ D’argenio, JM Covey and JL Eiseman. A mass balance and disposition study of the DNA methyltransferase inhibitor, zebularine (NSC 309132) and three of its metabolites in mice. Clinical Cancer Research 12:5826-5833, 2006
|
