Markos Leggas

Summary

Affiliation: University of Kentucky
Country: USA

Publications

  1. ncbi request reprint Validation of an HPLC method for analysis of DB-67 and its water soluble prodrug in mouse plasma
    Jamie Horn
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
    J Chromatogr B Analyt Technol Biomed Life Sci 844:15-22. 2006
  2. pmc Localization and functional characterization of the rat Oatp4c1 transporter in an in vitro cell system and rat tissues
    Kuei Ling Kuo
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky
    PLoS ONE 7:e39641. 2012
  3. ncbi request reprint Gefitinib modulates the function of multiple ATP-binding cassette transporters in vivo
    Markos Leggas
    Departments of Pharmaceutical Sciences, Hematology Oncology, and Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cancer Res 66:4802-7. 2006
  4. pmc The effect of breast cancer resistance protein, multidrug resistant protein 1, and organic anion-transporting polypeptide 1B3 on the antitumor efficacy of the lipophilic camptothecin 7-t-butyldimethylsilyl-10-hydroxycamptothecin (AR-67) in vitro
    Eleftheria Tsakalozou
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
    Drug Metab Dispos 41:1404-13. 2013
  5. ncbi request reprint Substrate overlap between Mrp4 and Abcg2/Bcrp affects purine analogue drug cytotoxicity and tissue distribution
    Kazumasa Takenaka
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA
    Cancer Res 67:6965-72. 2007
  6. ncbi request reprint Gefitinib enhances the antitumor activity and oral bioavailability of irinotecan in mice
    Clinton F Stewart
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Cancer Res 64:7491-9. 2004
  7. pmc Mrp4 confers resistance to topotecan and protects the brain from chemotherapy
    Markos Leggas
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, TN 38105 2794, USA
    Mol Cell Biol 24:7612-21. 2004
  8. doi request reprint Pharmacokinetic modeling to assess factors affecting the oral bioavailability of the lactone and carboxylate forms of the lipophilic camptothecin analogue AR-67 in rats
    Eyob D Adane
    Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky 40536, USA
    Pharm Res 29:1722-36. 2012
  9. pmc Stereoselective interaction of pantoprazole with ABCG2. II. In vitro flux analysis
    Lipeng Wang
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, Lexington, Kentucky 40536, USA
    Drug Metab Dispos 40:1024-31. 2012
  10. pmc N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918) as a chemical ATP-binding cassette transporter family G member 2 (Abcg2) knockout model to study nitrofurantoin transfe
    Lipeng Wang
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, KY 40536, USA
    Drug Metab Dispos 36:2591-6. 2008

Research Grants

Collaborators

Detail Information

Publications31

  1. ncbi request reprint Validation of an HPLC method for analysis of DB-67 and its water soluble prodrug in mouse plasma
    Jamie Horn
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
    J Chromatogr B Analyt Technol Biomed Life Sci 844:15-22. 2006
    ..The assay was found to be suitable for the analysis of DB-67 lactone and carboxylate in pharmacokinetic studies following intravenous administration of DB-67 or its delta-aminobutyric acid ester derivative...
  2. pmc Localization and functional characterization of the rat Oatp4c1 transporter in an in vitro cell system and rat tissues
    Kuei Ling Kuo
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky
    PLoS ONE 7:e39641. 2012
    ..These data definitively demonstrate the subcellular localization and histological location of Oatp4c1 and provide additional functional evidence that reconciles expression-function reports found in the literature...
  3. ncbi request reprint Gefitinib modulates the function of multiple ATP-binding cassette transporters in vivo
    Markos Leggas
    Departments of Pharmaceutical Sciences, Hematology Oncology, and Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cancer Res 66:4802-7. 2006
    ..4-AQ molecules may offer a means to increase the low and variable oral drug absorption of transporter substrates while decreasing interpatient variability and reversing tumor drug resistance...
  4. pmc The effect of breast cancer resistance protein, multidrug resistant protein 1, and organic anion-transporting polypeptide 1B3 on the antitumor efficacy of the lipophilic camptothecin 7-t-butyldimethylsilyl-10-hydroxycamptothecin (AR-67) in vitro
    Eleftheria Tsakalozou
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
    Drug Metab Dispos 41:1404-13. 2013
    ..In conclusion, BCRP- and MDR1-mediated efflux of AR-67 lactone confers resistance to AR-67, but OATP1B3-mediated uptake of the AR-67 carboxylate does not sensitize OATP1B3-expressing tumor cells...
  5. ncbi request reprint Substrate overlap between Mrp4 and Abcg2/Bcrp affects purine analogue drug cytotoxicity and tissue distribution
    Kazumasa Takenaka
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA
    Cancer Res 67:6965-72. 2007
    ..This new knowledge will facilitate an understanding of how Abcg2 and Mrp4, separately and in combination, protect against purine analogue host toxicity as well as resistance to chemotherapy...
  6. ncbi request reprint Gefitinib enhances the antitumor activity and oral bioavailability of irinotecan in mice
    Clinton F Stewart
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Cancer Res 64:7491-9. 2004
    ....
  7. pmc Mrp4 confers resistance to topotecan and protects the brain from chemotherapy
    Markos Leggas
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, TN 38105 2794, USA
    Mol Cell Biol 24:7612-21. 2004
    ....
  8. doi request reprint Pharmacokinetic modeling to assess factors affecting the oral bioavailability of the lactone and carboxylate forms of the lipophilic camptothecin analogue AR-67 in rats
    Eyob D Adane
    Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky 40536, USA
    Pharm Res 29:1722-36. 2012
    ..Such treatment is best suited for oral formulations. AR-67 is a novel lipophilic analogue with potent efficacy in preclinical models. Here we assessed factors that may influence its oral bioavailability in rats...
  9. pmc Stereoselective interaction of pantoprazole with ABCG2. II. In vitro flux analysis
    Lipeng Wang
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, Lexington, Kentucky 40536, USA
    Drug Metab Dispos 40:1024-31. 2012
    ..PAN is a better substrate than (+)PAN for ABCG2/rAbcg2 and provide a rationale for the preferential accumulation of (-)PAN into rat milk...
  10. pmc N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918) as a chemical ATP-binding cassette transporter family G member 2 (Abcg2) knockout model to study nitrofurantoin transfe
    Lipeng Wang
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, KY 40536, USA
    Drug Metab Dispos 36:2591-6. 2008
    ..GF120918 is particularly useful as a rat chemical knockout model to establish ABCG2's role in drug transfer into milk during breastfeeding...
  11. pmc Pyramidamycins A-D and 3-hydroxyquinoline-2-carboxamide; cytotoxic benzamides from Streptomyces sp. DGC1
    Khaled A Shaaban
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0596, USA
    J Antibiot (Tokyo) 65:615-22. 2012
    ..Taxonomically, the amplified 500-bp 16 S rRNA fragment of the Streptomyces sp. DGC1 had 99% identity (BLAST search) to the 16S rRNA gene of Streptomyces atrovirens strain NRRL B-16357...
  12. pmc A phase I study of 7-t-butyldimethylsilyl-10-hydroxycamptothecin in adult patients with refractory or metastatic solid malignancies
    Susanne M Arnold
    Markey Cancer Center, University of Kentucky, Lexington, Kentucky 40536 0082, USA
    Clin Cancer Res 16:673-80. 2010
    ..EXPERIMENTAL DESIGN AND METHODS: AR-67 was infused over 1 hour daily five times, every 21 days, using an accelerated titration trial design. Plasma was collected on the 1st and 4th day of cycle 1 to determine pharmacokinetic parameters...
  13. pmc Metabolic pathways of the camptothecin analog AR-67
    Jamie Horn
    Department of Pharmaceutical Science, College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA
    Drug Metab Dispos 39:683-92. 2011
    ....
  14. doi request reprint Intensive anti-inflammatory therapy with dexamethasone in patients with non-small cell lung cancer: effect on chemotherapy toxicity and efficacy
    Markos Leggas
    Department of Pharmaceutical Sciences, The College of Pharmacy, University of Kentucky, Lexington, KY, USA
    Cancer Chemother Pharmacol 63:731-43. 2009
    ..To translate these findings to patients, we have undertaken a Phase 1/2 clinical trial...
  15. ncbi request reprint Factors affecting the in vivo lactone stability and systemic clearance of the lipophilic camptothecin analogue AR-67
    Eyob D Adane
    Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky 40536, USA
    Pharm Res 27:1416-25. 2010
    ..Here we determined the disposition of the lactone and carboxylate forms of AR-67, a 3(rd) generation camptothecin analogue...
  16. ncbi request reprint Microbore HPLC method with online microdialysis for measurement of topotecan lactone and carboxylate in murine CSF
    Markos Leggas
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    J Pharm Sci 93:2284-95. 2004
    ..The system allows for the determination of TPT pharmacokinetics in murine CSF and provides a tool to extend pharmacological studies in this brain compartment...
  17. pmc Nanoparticles containing anti-inflammatory agents as chemotherapy adjuvants: optimization and in vitro characterization
    Xiuling Lu
    Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky 40536 0082, USA
    AAPS J 10:133-40. 2008
    ....
  18. ncbi request reprint Dependence of nelfinavir brain uptake on dose and tissue concentrations of the selective P-glycoprotein inhibitor zosuquidar in rats
    Bradley D Anderson
    University of Kentucky, Department of Pharmaceutical Sciences, ASTeCC Bldg, Room A323A, Lexington, KY 40506 0286, USA
    Drug Metab Dispos 34:653-9. 2006
    ....
  19. pmc Reducing signs of aging and increasing lifespan by drug synergy
    Xinhe Huang
    Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, 741 S Limestone, Lexington, KY 40536, USA
    Aging Cell 12:652-60. 2013
    ..Thus, our data show that it ought to be possible to find pharmacological approaches to generate a synergistic reduction in the incidence of human age-related diseases to improve health quality in the elderly and enhance lifespan. ..
  20. doi request reprint Pharmacologic properties of polyethylene glycol-modified Bacillus thiaminolyticus thiaminase I enzyme
    Shuqian Liu
    Department of Pediatrics, College of Medicine, University of Kentucky, Lexington, KY 40536, USA
    J Pharmacol Exp Ther 341:775-83. 2012
    ..These studies suggest that the mechanism of anticancer cytotoxicity of thiaminase requires acute depression of cellular respiration, whereas systemic toxicity is related to the duration of extracellular thiamine depletion...
  21. ncbi request reprint Protracted dosing of the lipophilic camptothecin analogue AR-67 in non-small cell lung cancer xenografts and humans
    Eleftheria Tsakalozou
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 S Limestone St, Room 323, Lexington, KY, 40536, USA
    Cancer Chemother Pharmacol 74:45-54. 2014
    ..To maximize the therapeutic potential of AR-67, we sought to identify factors that affect response to treatment...
  22. doi request reprint Abrogation of microcystin cytotoxicity by MAP kinase inhibitors and N-acetyl cysteine is confounded by OATPIB1 uptake activity inhibition
    Abigail Daily
    Department of Pediatrics, College of Medicine, University of Kentucky, Lexington, KY 40536, USA
    Toxicon 55:827-37. 2010
    ..Finally, growth of OATP1B1-expressing HeLa xenografts was inhibited by MCLR, suggesting that MCLR structural analogs selected for a broader therapeutic index could target OATP-expressing tumors...
  23. doi request reprint Pharmacokinetics of high-dose simvastatin in refractory and relapsed chronic lymphocytic leukemia patients
    Tamer A Ahmed
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 40536, USA
    Cancer Chemother Pharmacol 72:1369-74. 2013
    ..To evaluate the pharmacokinetics of simvastatin at the maximum tolerated dose (MTD) of 7.5 mg/kg, twice daily, in the context of a pilot trial enrolling patients with recurrent and refractory chronic lymphocytic leukemia...
  24. ncbi request reprint Progesterone acts via progesterone receptors A and B to regulate breast cancer resistance protein expression
    Mary Vore
    Graduate Center for Toxicology, University of Kentucky, 1095 VA Dr, 306 HSRB, Lexington, KY 40536 0305, USA
    Mol Pharmacol 73:613-5. 2008
    ..This issue of Molecular Pharmacology includes a study (p. 845) now conclusively demonstrating that progesterone acts via the progesterone A and B receptors to regulate BCRP expression in a placental cell line...
  25. pmc Saquayamycins G-K, cytotoxic angucyclines from Streptomyces sp. Including two analogues bearing the aminosugar rednose
    Khaled A Shaaban
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, Kentucky 40536 0596, USA
    J Nat Prod 75:1383-92. 2012
    ..3 and 3.9 μM, respectively. The results presented here provide more insights into the structure-activity relationship of saquayamycins with respect to the nature, number, and linkage of sugar residues...
  26. pmc Biodistribution and bioimaging studies of hybrid paclitaxel nanocrystals: lessons learned of the EPR effect and image-guided drug delivery
    Christin P Hollis
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington 40536, USA
    J Control Release 172:12-21. 2013
    ....
  27. ncbi request reprint Relation between Irofulven (MGI-114) systemic exposure and tumor response in human solid tumor xenografts
    Markos Leggas
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Clin Cancer Res 8:3000-7. 2002
    ....
  28. ncbi request reprint Sunitinib malate for the treatment of metastatic renal cell carcinoma and gastrointestinal stromal tumors
    Val R Adams
    Department of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536, USA
    Clin Ther 29:1338-53. 2007
    ....
  29. doi request reprint Nanotemplate-engineered nanoparticles containing gadolinium for magnetic resonance imaging of tumors
    Donghua Zhu
    Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky 40536 0082, USA
    Invest Radiol 43:129-40. 2008
    ..To design nanoparticles containing accessible gadolinium atoms (Gd-NPs) as a contrast agent for magnetic resonance imaging of tumors...
  30. pmc Stable RNA nanoparticles as potential new generation drugs for cancer therapy
    Yi Shu
    Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536, USA
    Adv Drug Deliv Rev 66:74-89. 2014
    ..The methods for RNA nanoparticle construction, and the current challenges in the clinical application of RNA nanotechnology, such as endosome trapping and production costs, are also discussed. ..
  31. ncbi request reprint Interactions between hepatic Mrp4 and Sult2a as revealed by the constitutive androstane receptor and Mrp4 knockout mice
    Mahfoud Assem
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Biol Chem 279:22250-7. 2004
    ....

Research Grants2

  1. Phase I and Biological Studies of DB67 - A Blood Stable Camptothecin
    Markos Leggas; Fiscal Year: 2007
    ..Ultimately, the objective is to use DB-67 as a single agent or in combination with other molecular-targeted therapies or cytotoxics in frontline therapy with the goal to improve overall patient outcome. ..