Markos Leggas, Ph.D.
Dr. Leggas joined the University of Kentucky College of Pharmacy in 2004 and his research efforts have focused on translational projects in the area of anticancer drug development. Currently, Dr. Leggas has NCI and industrial funding for the clinical development of a novel anticancer agent, DB-67, which is in Phase I clinical trials.
Another major emphasis of the laboratory is placed in the pharmacokinetics and pharmacodynamics of nanoparticle and/or liposomal anticancer drug formulations. In addition Dr. Leggas is studying the role of transporter proteins on the disposition of physiological substrates and anticancer drugs as well as in the development of tumor drug resistance.
- Horn J, Milewska M, Arnold SM, Leggas M. Metabolism Pathways of the Blood Stable Camptothecin Analogue AR-67. Drug Metab Dispos. (epub ahead of print, Dec. 28, 2010)
- Adane ED, Liu Z, Xiang TX, Anderson BD, Leggas M. Factors Affecting the In Vivo Lactone Stability and Systemic Clearance of the Lipophilic Camptothecin Analogue AR-67. Pharm Res. 2010;27(7):1416-25.
- Tsakalozou E, Horn J, Leggas M. An HPLC Assay for the Lipophilic Camptothecin Analog AR-67 Carboxylate and Lactone in Human Whole Blood. Biomedical Chromatography 2010;24(10):1045-51.
- Arnold SM, Rinehart JJ, Tsakalozou E, Eckardt JR, Fields SZ, Shelton BJ, DeSimone PA, Kee BK, Moscow JA, Leggas M. A Phase 1 Study of 7-t-butyldimethylsilyl-10-hydroxycamptothecin (AR-67) in Adult Patients with Refractory or Metastatic Solid Malignancies. Clinical Cancer Research, 2010;16(2): 673-80.
- Daily A, Monks NR, Leggas M, Moscow JA. Abrogation of microcystin cytotoxicity by MAP kinase inhibitors and N-acetyl cysteine is confounded by OATPIB1 uptake activity inhibition. Toxicon. 2010;55(4):827-37.
- Wilson MW, Fraga CH, Rodriguez-Galindo C, Hagedorn N, Leggas M, Stewart C. Expression of the multi-drug resistance proteins and the pregnane X receptor in treated and untreated retinoblastoma. Curr Eye Res. 2009;34(5):386-94.
- Lu X, Howard MD, Talbert DR, Rinehart JJ, Potter PM, Jay M, Leggas M. Nanoparticles Containing Anti-Inflammatory Agents as Chemotherapy Adjuvants II: Role of Plasma Esterases in Drug Release. AAPS J. 2009; 11(1): 120-122.
- Ma P, Dong X, Swadley CL, Gupte A, Leggas M, Ledebur HC, Mumper RJ. Development of Idarubicin and Doxorubicin Solid Lipid Nanoparticles to Overcome Pgp–mediated Multiple Drug Resistance in Leukemia. Conditionally accepted Journal of Biomedical Nanotechnology, 2009; 5(2): 151-161.
- Wang L, Leggas M, Goswami M, Empey PE, McNamara PJ. N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridinecarboxamide (GF120918) as a chemical ATP-binding cassette transporter family G member 2 (Abcg2) knockout model to study nitrofurantoin transfer into milk. Drug Metab Dispos. 2008;36(12):2591-6.
- Leggas M, Kuo KL, Robert F, Cloud G, Deshazo M, Zhang R, Li M, Wang H, Davidson S, Rinehart JJ. Intensive anti-inflammatory therapy with dexamethasone in patients with non-small cell lung cancer: effect on chemotherapy toxicity and efficacy. Cancer Chemother Pharmacol. 2008; 63(4):731-743.
- Lu X, Howard MD, Mazik M, Eldridge J, Rinehart JJ, Jay M, Leggas M. Nanoparticles containing anti-inflammatory agents as chemotherapy adjuvants: optimization and in vitro characterization. AAPS J. 2008;10: 133-40.
- Zhu D, Lu X, Hardy PA, Leggas M, Jay M. Nanotemplate-engineered nanoparticles containing gadolinium for magnetic resonance imaging of tumors. Invest Radiol 2008;43: 129-40.
- Vore M, Leggas M. Progesterone acts via progesterone receptors A and B to regulate breast cancer resistance protein expression. Mol Pharmacol 2008;73: 613-5.
- Adams VR, Leggas M. Sunitinib malate for the treatment of metastatic renal cell carcinoma and gastrointestinal stromal tumors. Clin Ther 2007;29: 1338-53.
- Takenaka K, Morgan JA, Scheffer GL, Adachi M, Stewart CF, Sun D, Leggas M, Ejendal KF, Hrycyna CA, Schuetz JD. Substrate overlap between Mrp4 and Abcg2/Bcrp affects purine analogue drug cytotoxicity and tissue distribution. Cancer Res 2007;67: 6965-72.
- Horn J, Jordan SL, Song L, Roberts MJ, Anderson BD, Leggas M. Validation of an HPLC method for analysis of DB-67 and its water soluble prodrug in mouse plasma. J Chromatogr B Analyt Technol Biomed Life Sci 2006;844: 15-22.
- Leggas M, Panetta JC, Zhuang Y, Schuetz JD, Johnston B, Bai F, Sorrentino B, Zhou S, Houghton PJ, Stewart CF. Gefitinib modulates the function of multiple ATP-binding cassette transporters in vivo. Cancer Res 2006;66: 4802-7.
- Wilson MW, Fraga CH, Fuller CE, Rodriguez-Galindo C, Mancini J, Hagedorn N, Leggas M, Stewart CF. Immunohistochemical detection of multidrug-resistant protein expression in retinoblastoma treated by primary enucleation. Invest Ophthalmol Vis Sci 2006;47: 1269-73.
- Anderson BD, May MJ, Jordan S, Song L, Roberts MJ, Leggas M. Dependence of nelfinavir brain uptake on dose and tissue concentrations of the selective P-glycoprotein inhibitor zosuquidar in rats. Drug Metab Dispos 2006;34: 653-9.
- Laurie NA, Gray JK, Zhang J, Leggas M, Relling M, Egorin M, Stewart C, Dyer MA. Topotecan combination chemotherapy in two new rodent models of retinoblastoma. Clinical Cancer Research 2005;11: 7569-78.
- Stewart CF, Leggas M, Schuetz JD, Panetta JC, Cheshire PJ, Peterson J, Daw N, Jenkins JJ, 3rd, Gilbertson R, Germain GS, Harwood FC, Houghton PJ. Gefitinib enhances the antitumor activity and oral bioavailability of irinotecan in mice. Cancer Res 2004;64: 7491-9.
- Leggas M, Adachi M, Scheffer GL, Sun D, Wielinga P, Du G, Mercer KE, Zhuang Y, Panetta JC, Johnston B, Scheper RJ, Stewart CF, Schuetz JD. Mrp4 confers resistance to topotecan and protects the brain from chemotherapy. Mol Cell Biol 2004;24: 7612-21.
- Leggas M, Zhuang Y, Welden J, Self Z, Waters CM, Stewart CF. Microbore HPLC method with online microdialysis for measurement of topotecan lactone and carboxylate in murine CSF. J Pharm Sci 2004;93: 2284-95.
- Assem M, Schuetz EG, Leggas M, Sun D, Yasuda K, Reid G, Zelcer N, Adachi M, Strom S, Evans RM, Moore DD, Borst P, Schuetz JD. Interactions between hepatic Mrp4 and Sult2a as revealed by the constitutive androstane receptor and Mrp4 knockout mice. J Biol Chem 2004;279: 22250-7.
- Leggas M, Stewart CF, Woo MH, Fouladi M, Cheshire PJ, Peterson JK, Friedman HS, Billups C, Houghton PJ. Relation between Irofulven (MGI-114) systemic exposure and tumor response in human solid tumor xenografts. Clin Cancer Res 2002;8: 3000-7.