Research Topics
Species | Julie L EisemanSummaryAffiliation: University of Pittsburgh Country: USA Publications
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Publications
Pharmacokinetics and tissue distribution of inositol hexaphosphate in C.B17 SCID mice bearing human breast cancer xenograftsJulie Eiseman
Molecular Therapeutics and Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
Metabolism 60:1465-74. 2011..After both IV and PO administration, exogenous IP(6) was rapidly dephosphorylated to inositol; however, alterations in endogenous IPs were not examined...
Evaluation of plasma insulin-like growth factor binding protein 2 and Her-2 extracellular domain as biomarkers for 17-allylamino-17-demethoxygeldanamycin treatment of adult patients with advanced solid tumorsJulie L Eiseman
Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213 1863, USA
Clin Cancer Res 13:2121-7. 2007..Pretreatment plasma samples were also obtained from 12 healthy volunteers. Plasma IGFBP-2 and Her-2 ECD concentrations were quantitated by ELISA...- Distribution of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) uracil in mice bearing colorectal cancer xenografts: rationale for therapeutic use and as a positron emission tomography probe for thymidylate synthaseJulie L Eiseman
Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213 1863, USA
Clin Cancer Res 10:6669-76. 2004..These studies were designed to evaluate FAU as a potential therapeutic and diagnostic probe... - Pharmacokinetics and pharmacodynamics of 17-demethoxy 17-[[(2-dimethylamino)ethyl]amino]geldanamycin (17DMAG, NSC 707545) in C.B-17 SCID mice bearing MDA-MB-231 human breast cancer xenograftsJulie L Eiseman
Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Cancer Chemother Pharmacol 55:21-32. 2005..v. delivery to mice; and (2) correlated tumor and normal tissue 17DMAG concentrations with alterations in heat shock protein 90 (HSP90) and selected HSP90-chaperoned proteins... 
Improved synthesis of 6-epi-dictyostatin and antitumor efficacy in mice bearing MDA-MB231 human breast cancer xenograftsJulie L Eiseman
Department of Pharmacology and Chemical Biology and University of Pittsburgh Cancer Institute, G 27 b Research Pavilion, Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, Pennsylvania 15213 1862, USA
J Med Chem 51:6650-3. 2008..Here we describe a new total synthesis that produced more than 30 mg of 6- epi-dictyostatin. The compound was found to have potent antitumor activity in SCID mice bearing MDA-MB231 human breast cancer xenografts...- Systemic and tumor disposition of platinum after administration of cisplatin or STEALTH liposomal-cisplatin formulations (SPI-077 and SPI-077 B103) in a preclinical tumor model of melanomaWilliam C Zamboni
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213, USA
Cancer Chemother Pharmacol 53:329-36. 2004..Thus, we evaluated the disposition of encapsulated and released Pt in plasma and tumors after administration of STEALTH liposomal and nonliposomal cisplatin... - Plasma pharmacokinetics and oral bioavailability of 3,4,5,6-tetrahydrouridine, a cytidine deaminase inhibitor, in miceJan H Beumer
Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
Cancer Chemother Pharmacol 62:457-64. 2008..This suggests the feasibility of using THU to decrease elimination and first-pass metabolism of cytidine analogues by CD. THU pharmacokinetics are now being evaluated in humans... - Pharmacology and antitumor activity of a quinolinedione Cdc25 phosphatase inhibitor DA3003-1 (NSC 663284)Jianxia Guo
Departments of Pharmacology, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, 15261, USA
Anticancer Res 27:3067-73. 2007..These studies suggest that the minimal antitumor activity of DA3003-1 in mice may be due to its rapid metabolism... - Tumor, tissue, and plasma pharmacokinetic studies and antitumor response studies of docetaxel in combination with 9-nitrocamptothecin in mice bearing SKOV-3 human ovarian xenograftsWilliam C Zamboni
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213, USA
Cancer Chemother Pharmacol 62:417-26. 2008.... - Relationship between plasma exposure of 9-nitrocamptothecin and its 9-aminocamptothecin metabolite and antitumor response in mice bearing human colon carcinoma xenograftsWilliam C Zamboni
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pennsylvania 15213 1863, USA
Clin Cancer Res 11:4867-74. 2005..These results suggest that the intermittent schedule of 9-nitrocamptothecin may be an active regimen in patients with colorectal carcinoma... - Efficacy, pharmacokinetics, tisssue distribution, and metabolism of the Myc-Max disruptor, 10058-F4 [Z,E]-5-[4-ethylbenzylidine]-2-thioxothiazolidin-4-one, in miceJianxia Guo
Hillman Cancer Center, The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
Cancer Chemother Pharmacol 63:615-25. 2009..In vitro studies indicate the thioxothiazolidinone, 10058-F4, inhibits c-Myc/Max dimerization. In this study, we report the efficacy, pharmacokinetics and metabolism of this novel protein-protein disruptor in mice... - Plasma pharmacokinetics and oral bioavailability of the 3,4,5,6-tetrahydrouridine (THU) prodrug, triacetyl-THU (taTHU), in miceJan H Beumer
Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Hillman Research Pavilion, Room G27D, 5117 Centre Avenue, Pittsburgh, PA 5213 1863, USA
Cancer Chemother Pharmacol 67:421-30. 2011..Therefore, we characterized THU pharmacokinetics after the administration to mice of the more lipophilic pro-drug triacetyl-THU (taTHU)... - Plasma and tissue disposition of non-liposomal DB-67 and liposomal DB-67 in C.B-17 SCID miceWilliam C Zamboni
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, 15213, USA
Invest New Drugs 26:399-406. 2008..We evaluated the tissue and plasma disposition of DB-67 lactone and hydroxy acid after administration of non-liposomal (NL) and liposomal (L) DB-67 in severe combined immunodeficient (SCID) mice... - Phase I and pharmacodynamic study of 17-(allylamino)-17-demethoxygeldanamycin in adult patients with refractory advanced cancersRamesh K Ramanathan
Division of Hematology Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA
Clin Cancer Res 13:1769-74. 2007..The primary objective was to establish the dose-limiting toxicity (DLT) and recommended phase II dose of 17-(allylamino)-17-demethoxygeldanamycin (17AAG) given twice a week... - Modulation of gemcitabine (2',2'-difluoro-2'-deoxycytidine) pharmacokinetics, metabolism, and bioavailability in mice by 3,4,5,6-tetrahydrouridineJan H Beumer
Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Room G 27d, Hillman Research Pavilion, 5117 Centre Avenue, Pittsburgh, PA 15213 1863, USA
Clin Cancer Res 14:3529-35. 2008..3,4,5,6-Tetrahydrouridine (THU) is a potent CD inhibitor with a 20% oral bioavailability. We investigated the ability of THU to decrease elimination and first-pass effect by CD, thereby enabling oral dosing of dFdC... - Plasma, tumor, and tissue disposition of STEALTH liposomal CKD-602 (S-CKD602) and nonliposomal CKD-602 in mice bearing A375 human melanoma xenograftsWilliam C Zamboni
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Clin Cancer Res 13:7217-23. 2007..For STEALTH liposomal formulations of anticancer agents to achieve antitumor effects, the active drug must be released into the tumor extracellular fluid (ECF)... - Noninvasive and nondestructive optical spectroscopic measurement of motexafin gadolinium in mouse tissues: comparison to high-performance liquid chromatographyStephen C Kanick
Department of Chemical Engineering, University of Pittsburgh, School of Engineering, Pittsburgh, PA 15261, USA
J Photochem Photobiol B 88:90-104. 2007..900 and 1.185, respectively; however, the variability was significant (r(2)=0.477 and 0.269). The clinical utility of the OPS to quantitate MGd concentrations remains to be validated... - A mass balance and disposition study of the DNA methyltransferase inhibitor zebularine (NSC 309132) and three of its metabolites in miceJan H Beumer
Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh, PA 15213, USA
Clin Cancer Res 12:5826-33. 2006..To elucidate the in vivo metabolic fate of zebularine (NSC 309132), a DNA methyltransferase inhibitor proposed for clinical evaluation in the treatment of cancer... - In vitro cytotoxicity and in vivo efficacy, pharmacokinetics, and metabolism of 10074-G5, a novel small-molecule inhibitor of c-Myc/Max dimerizationDana M Clausen
Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA
J Pharmacol Exp Ther 335:715-27. 2010..Our identification of 10074-G5 metabolites in mice will help design new, more metabolically stable small-molecule inhibitors of c-Myc... - Pharmacokinetic modeling of motexafin gadolinium disposition in mouse tissues using optical pharmacokinetic system measurementsStephen C Kanick
Department of Chemical Engineering, University of Pittsburgh School of Engineering, Pittsburgh, PA 15261, USA
Photodiagnosis Photodyn Ther 5:276-84. 2008..The PK modeling techniques presented here are extensible to other optically active compounds and, potentially, to the development of patient-specific treatment schedules... - Quantitative determination of the cytidine deaminase inhibitor tetrahydrouridine (THU) in mouse plasma by liquid chromatography/electrospray ionization tandem mass spectrometryRobert A Parise
Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
Rapid Commun Mass Spectrom 21:1991-7. 2007..This assay is currently being used to quantitate THU in ongoing pharmacokinetic studies. In addition, the assay is expected to be a useful tool in any future studies involving co-administration of THU with cytidine analogues... - Plasma pharmacokinetics, oral bioavailability, and interspecies scaling of the DNA methyltransferase inhibitor, zebularineJulianne L Holleran
Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA
Clin Cancer Res 11:3862-8. 2005..Interspecies scaling produced the following relationship: CL(tb) = 6.46(weight(0.9)). CONCLUSIONS: Zebularine has limited oral bioavailability. Interspecies scaling projects a CL(tb) of 296 mL/min in humans... - Phase I pharmacokinetic-pharmacodynamic study of 17-(allylamino)-17-demethoxygeldanamycin (17AAG, NSC 330507), a novel inhibitor of heat shock protein 90, in patients with refractory advanced cancersRamesh K Ramanathan
Molecular Therapeutics Drug Discovery Program, Biostatistics Department, Graduate School of Public Health, and Biostatistics Facility, University of Pittsburgh Cancer Institute, PA 15232, USA
Clin Cancer Res 11:3385-91. 2005..We did a phase I study of 17AAG to establish the dose-limiting toxicity and maximum tolerated dose and to characterize 17AAG pharmacokinetics and pharmacodynamics... - Inter- and intratumoral disposition of platinum in solid tumors after administration of cisplatinWilliam C Zamboni
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
Clin Cancer Res 8:2992-9. 2002..There was no relationship between Factor VIII expression and Pt exposure in tumors. The variable penetration of Pt from plasma into tumor ECF may be associated with variable response of tumors... - Control-relevant modeling of the antitumor effects of 9-nitrocamptothecin in SCID mice bearing HT29 human colon xenograftsJohn M Harrold
Department of Chemical and Petroleum Engineering, University of Pittsburgh School of Engineering, Pittsburgh, PA 15261, USA
J Pharmacokinet Pharmacodyn 32:65-83. 2005..This methodology could then be used to aid the clinician in selecting dose levels and schedules, and extension to patient tailored treatment may eventually be feasible with this approach... - Pharmacokinetics, metabolism, and oral bioavailability of the DNA methyltransferase inhibitor 5-fluoro-2'-deoxycytidine in miceJan H Beumer
Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, PA 15213 1863, USA
Clin Cancer Res 12:7483-91. 2006..However, the full effects of THU on FdCyd metabolism and pharmacokinetics are unknown. We aimed to characterize the pharmacokinetics, metabolism, and bioavailability of FdCyd with and without THU in mice... - Quantitative determination of zebularine (NSC 309132), a DNA methyltransferase inhibitor, and three metabolites in murine plasma by high-performance liquid chromatography coupled with on-line radioactivity detectionJan H Beumer
Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
J Chromatogr B Analyt Technol Biomed Life Sci 831:147-55. 2006..5-50 microg/mL for uridine, 1.0-10 microg/mL for uracil and 0.5-5.0 microg/mL for dihydrouracil. This assay is being used to quantitate zebularine and its metabolites in ongoing pharmacokinetic studies of zebularine... - Nonlinear model predictive control for dosing daily anticancer agents using a novel saturating-rate cell-cycle modelJeffry A Florian
Department of Chemical and Petroleum Engineering, University of Pittsburgh School of Engineering, Pittsburgh, PA, USA
Comput Biol Med 38:339-47. 2008..Overall, the NMPC algorithm is suitable for dosing chemotherapeutics with regular administration schedules and may be adapted for regularly administered chemotherapeutics other than tamoxifen... - Liquid chromatography-tandem mass spectrometric assay for the quantitation in human plasma of the novel indenoisoquinoline topoisomerase I inhibitors, NSC 743400 and NSC 725776Julianne L Holleran
Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh, PA 15213, USA
J Pharm Biomed Anal 52:714-20. 2010..Protein binding in human plasma as assessed by equilibrium dialysis showed both indenoisoquinolines to be more than 98% protein bound... - Pharmacokinetics, tissue distribution, and metabolism of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (NSC 707545) in CD2F1 mice and Fischer 344 ratsMerrill J Egorin
Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, PA 15213, USA
Cancer Chemother Pharmacol 49:7-19. 2002..p. and oral delivery; (3) characterize the biliary excretion of 17DMAG after i.v. delivery to rats; and (4) characterize, if possible, any metabolites of 17DMAG observed in plasma, tissue, urine, or bile... - Phase I and pharmacokinetic study of the novel redox-active agent, motexafin gadolinium, with concurrent radiation therapy in patients with locally advanced pancreatic or biliary cancersRamesh K Ramanathan
Division of Hematology Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Cancer Chemother Pharmacol 57:465-74. 2006..The pharmacokinetics of MGd were also evaluated... - The relationship of phthalocyanine 4 (pc 4) concentrations measured noninvasively to outcome of pc 4 photodynamic therapy in miceLihua Bai
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Photochem Photobiol 85:1011-9. 2009..86). In excised tumors, OPS-measured Pc 4 concentrations were similar to the HPLC-measured concentrations. Thus, OPS measurements of photosensitizer concentrations can be used to assist in the scheduling of Pc 4-PDT... - Liquid chromatography-mass spectrometric assay for quantitation of the short-chain fatty acid, 2,2-dimethylbutyrate (NSC 741804), in rat plasmaRobert A Parise
Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
J Chromatogr B Analyt Technol Biomed Life Sci 862:168-74. 2008..The assay was accurate (97-107%) and precise (3.4-6.2%) between 100 and 10,000ng/mL. Recovery from plasma was >62%. Plasma freeze-thaw and room temperature stability were acceptable... - In vitro metabolism of the phosphatidylinositol 3-kinase inhibitor, wortmannin, by carbonyl reductaseJulianne L Holleran
University of Pittsburgh Cancer Institute, Room G27E, Hillman Research Pavilion, 5117 Centre Avenue, Pittsburgh, PA 15213-1863
Drug Metab Dispos 32:490-6. 2004..Metabolism of wortmannin to 17-OH-wortmannin has mechanistic, and possibly toxicologic, implications because 17-OH-wortmannin is 10-fold more potent an inhibitor of phosphatidylinositol 3-kinase than is wortmannin... - Formation of active products of benzaldehyde dimethane sulfonate (NSC 281612, DMS612) in human blood and plasma and their activity against renal cell carcinoma linesRobert A Parise
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, 15213, USA
Cancer Chemother Pharmacol 71:73-83. 2013..The information gained from these experiments will be instrumental in the evaluation of the pharmacology of BEN in ongoing human trials... - Inducible silencing of protein kinase D3 inhibits secretion of tumor-promoting factors in prostate cancerCourtney R LaValle
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
Mol Cancer Ther 11:1389-99. 2012..These data validate PKD3 as a promising therapeutic target in prostate cancer and shed light on the role of secreted tumor-promoting factors in prostate cancer progression... - Physiologically-based pharmacokinetics and molecular pharmacodynamics of 17-(allylamino)-17-demethoxygeldanamycin and its active metabolite in tumor-bearing miceLu Xu
Department of Biomedical Engineering, University of Southern California, University Park, Los Angeles, CA 90089, USA
J Pharmacokinet Pharmacodyn 30:185-219. 2003..In modeling pharmacokmetics and pharmacodynamics, Bayesian inference was employed to estimate the kinetic, physiological and molecular parameters when prior information was available... - N-(2-hydroxypropyl)methacrylamide copolymers of a glutathione (GSH)-activated glyoxalase i inhibitor and DNA alkylating agent: synthesis, reaction kinetics with GSH, and in vitro antitumor activitiesZhe-Bin Zheng
Department of Chemistry and Biochemistry, University of Maryland, Baltimore, Maryland 21250, USA
Bioconjug Chem 16:598-607. 2005..This prodrug strategy should be applicable to a range of different GSH-based antitumor agents... - Biliary excretion of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) and metabolites by Fischer 344 ratsSteven M Musser
Instrumentation and Biophysics Branch, Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, MD 20740, USA
Cancer Chemother Pharmacol 52:139-46. 2003.... - Preclinical toxicity of a geldanamycin analog, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), in rats and dogs: potential clinical relevanceElizabeth R Glaze
Toxicology and Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Executive Plaza North, Room 8040, Rockville, MD 20852, USA
Cancer Chemother Pharmacol 56:637-47. 2005..In addition, 17-DMAG undergoes only limited metabolism compared to 17-AAG. The present results are from preclinical toxicity studies evaluating 17-DMAG in rats and dogs... - Selective inhibition of MCF-7(piGST) breast tumors using glutathione transferase-derived 2-methylene-cycloalkenonesErin Joseph
Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, MD 21250, USA
J Med Chem 48:6549-52. 2005..The COMCs are a potentially important new class of prodrugs, which can specifically target multi-drug-resistant tumors overexpressing hGSTP1-1... - Molecular basis of the antitumor activities of 2-crotonyloxymethyl-2-cycloalkenonesErin Joseph
Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, Maryland 21250, USA
J Med Chem 46:194-6. 2003..041 microM) and its five- and seven-membered ring homologues. Antitumor activity probably results from a reactive intermediate that forms during conjugation of the COMCs with intracellular GSH...