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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Important Publications

Eiseman J, J Lan, J Guo, E Joseph and Vucenik I.  Pharmacokinetics and tissue distribution of inositol hexaphosphate in C.B17 SCID mice bearing human breast cancer xenografts.  Metabolism 2011 Apr 11 [Epub ahead of print].

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 67:421-430, 2011.

Zamboni WC, Eiseman JL, S Strychor, PM Rice, E Joseph, BA Zamboni, MK Donnelly, J Shurer, RA Parise, ME Tonda, NY Yu and PH Basse.  Tumor disposition of pegylated liposomal CKD-602 and the reticuloendothelial system in preclinical tumor models.  J Liposome Res 21:70-80, 2011.

Clausen DM, J Guo, RA Parise, JH Beumer, MJ Egorin, JS Lazo, EV Prochownik and JL Eiseman.  In vitro cytotoxicity and in vivo efficacy, pharmacokinetics and metabolism of 10074-G5:  A novel small-molecule inhibitor of C-Myc/Max dimerization.  J Pharmacol Exp Ther 335:715-727, 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.

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.

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.

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.