Pharmacokinetics, metabolite and clinical pharmacokinetics; clinical studies; cancer drug development, drug metabolism, drug analytical method development, stable isotope labeling, liquid-chromatographic mass spectrometry, application of stable isotopes in pharmacokinetic and drug metabolism research, cancer chemotherapy and modulation, and antisense drug therapy.

 

Since 2003 (*MS related)

 

*Naasani, I, Oh-hashi, F, Oh-hara, T, Feng, WY, Johnston, J, Chan ,K, and Tsuruo,T.  Blocking  Telomerase by Dietary Polyphenols Is a Major Mechanism for Limiting the Growth of Human Cancer Cells in vitro and in vivo. Cancer Res. 63: 824-830, 2003.

 

*Xiao, JJ, Byrd, J,  Marcucci, G, Grever, M, and Chan, KK.* Identification of Thiols and Glutathione Conjugates of Depsipeptide FK228 (FR901228), a Novel Histone Protein Deacetylase Inhibitor, in the Blood. Rapid Comm Mass Spectrometry 17(8):757-766, 2003.

 

Klisovic, MI, Maghraby, EA, Parthun, R, Guimond, M, Sklenar, AR, Whitman, SP, Chan, KK, Murphy, T, Anon, J, Archer, KJ, Rush, LJ, Plass, C, Grever, MR, Byrd, JC, and Marcucci, G.* Depsipeptide (FR 901228) Promotes Histone Acetylation, Gene Transcription, Apoptosis, and its Activity is Enhanced by DNA Methyltransferase Inhibitors in AML1/ETO-positive leukemic cells. Leukemia 17:350-358, 2003.

 

Gao, H, Yamasaki, EF, Chan, KK, Shen, LL, and Snapka, RM.* DNA Sequence Specificity for Topoisomerase II Poisoning by the Quinoxaline Anticancer Drugs XK469 and CQS. Mol Pharmacol 63(6): 1382-1388, 2003.

 

Castelao, JE, Yuan, J-M, Gago-Dominguez, M, Skipper, PL, Tannenbaum, SR, Chan, KK, Watson, MA, Bell, DA, Coetzee, GA, Ross, RK, and Yu, MC. Carotenoids/vitamin C and Smoking-related Bladder Cancer. Int J Cancer 110: 417-423, 2004.

 

*Berg, SL, Stone, J, Xiao, JJ, Chan, KK, Nuchtern, J, Dauser, R, McGuffey, L, and Blaney SM. Plasma and Cerebrospinal Fluid Pharmacokinetics of Depsipeptide (FR901228) in Nonhuman Primates. Cancer Pharmacol Pharmacol 54(1):85-88, 2004.

 

*Hua, Y, Fan-Havard, P, and Chan, KK.* A Subnanogram On-line Column-switch LC/MS/MS Quantification Method for Nelfinavir and Methoxy-phenol Metabolite M1 in Rat Plasma. J Chromatog B 809(1): 1-7, 2004.

 

Marcucci, G, Stock, W, Dai, G, Klisovic, MI, Maharry, K, Shen, T, Liu, S, Larson, RA, Caliguiri, MA, Bloomfield, CD, Chan, KK, Grever, MR, Byrd, JC. G 3139, a BCL-2 antisense oligonucleotide, in AML. Ann Hematol. 83:S93-4, 2004.

 

Roychowdhury, S, Baiocchi, R, Vourganti, S, Bhatt, D, Blaser, BW, Freud, AG, Chou, J,Chen, Chang-Shi, Xiao, JJ, Parthun, M, Chan, KK, Eisenbeis, CF, Ferketich, AK, Grever, MR, Chen, Ching-Shih, and Caligiuri, MA. Selective Efficacy of Depsipeptide in a Xenograft Model of Epstein-Barr Virus-Positive Lymphoproliferative Disorder. J Natl Cancer Inst. 96(19): 4471457, 2004.

 

*Liu, Z, Floss, HG, Cassady, JM, Xiao, J, and Chan, KK.  An API LC/MS/MS Quantitation Method for Ansamitocin P-3 (AP3) and its Preclinical Pharmacokinetics. J Pharm Biomed Anal 36(4): 815-821, 2004.

 

*Liu, Z, Floss, HG, Cassady, JM, and Chan, KK.  Metabolism Studies of the Anti-tumor    Agent Maytansine and Its Analog Ansamitocin P-3 Using Liquid Chromatography/Tandem Mass Spectrometry. J Mass Spectrom. 40(3): 389-399, 2005.

 

John M. Cassady, Kenneth K. Chan, Heinz G. Floss, and Eckhard Leistner. Recent Developments in the maytansinoid antitumor agents. In Chem Pharm Bull, 52(1)1-26, 2004.  BOOK CHAPTER

 

*Xiao, JJ, Foraker, AB, Swaan, PW, Liu, S, Huang, Y, Dai, Z, Chen, J, Sadee, W, Byrd,J, Marcucci, G, and Chan KK. Efflux of Depsipeptide FK228 (FR901228, NSC-630176) is Mediated by both P-glycoprotein and MRP1. J Pharmacol Exp Thera. 313(1): 268-276, 2005.

 

*Byrd, JC,  Marcucci, G, Parthun, MR, Xiao, JJ, Klisovic, RB, Moran, M, Lin, TS, Liu, S, Wickham, J, Davis, ME, Lucas, DM, Fischer, B, Shank, R, Binkley, B, Wright, J, Chan, KK, and  Grever, MR. A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia. Blood 105(3): 959-957, 2005.

 

Otterson, GA, Lavelle, J, Villalona-Calero, MA, Shah, M, Wei, X, Chan, KK, Fischer, B, Grever, M. A Phase I Clinical and Pharmacokinetic Study of Fenretinide Combined with Paclitaxel and Cisplatin for Refractory Solid Tumors. Invest. New Drugs, 23(6): 555-562, 2005.

 

Xiao, JJ, Huang, Y, Dai, Z, Liu, S, Chen, J, Covey, JM, Wright, JM, Byrd, J, Marcucci, G,    Sadée, W and Chan, KK. Chemo-resistance to depsipeptide FK228 is mediated by reversible MDR1 induction in human cancer cell lines. J Pharmacol Exp Thera. 314(1): 467-475, 2005.

 

Huang, Y, Blower, PE, Yang, C, Barbacioru, C, Dai, Z, Zhang, Y, Xiao, JJ, Chan, KK, and  Sadée, W. Correlating gene expression with chemical scaffolds of cytotoxic agents: ellipticines as substrates and inhibitors of MDR1. The Pharmacogenomics Journal 5:112-125, 2005.

 

Dai, G, Chan, KK, Liu, S, Hoyt, D, Whitman, S, Klisovic, M, Shen, TS, Caliguri, MA, Byrd, J, Grever, M, and Marcucci, G. Cellular uptake and intracellular levels of the Bcl-2 antisense G3139 in cultured cells, and treated patients with acute myeloid leukemia. Clin Cancer Res, 11(8):2998-3008, 2005.

 

Marcucci, G, Stock, W, Dai, G, Klisovic, RB, Liu, S, Klisovic, MI, Blum, W, Kefauver, C,    Sher, DA, Green, M, Moran, M, Maharry, K, Novick, S, Bloomfield, CD, Zwiebel, JA, Larson, RA, Grever, MR, Chan, KK, and Byrd, JC.  Phase I Study of Oblimersen Sodium, an Antisense to Bcl-2, in Untreated Older Patients with Acute Myeloid Leukemia: Pharmacokinetics, Pharmacodynamics and Clinical Activity.  J Clin Oncology, 23(15): 3404-3411, 2005.

 

*Dai, G, Wei, X, Liu, Z, Liu, S, Marcucci, G, Chan, KK. Characterization and quantification of Bcl-2 antisense G3139 and metabolites in plasma and urine by ion-pair reversed phase HPLC coupled with electrospray ion-trap mass spectrometry.  J Chromatogr B 825(2): 201-213, 2005. (Invited manuscript)

 

*Liu, Z, Chan, KK, and Wang, JJ. Tandem mass spectrometric analysis of cyclophosphamide, ifosfamide and their metabolites. Rapid Comm Mass Spectrom, 19(18): 2581-2590, 2005.

 

Bekaii-Saab, T, Mortazavi, A, Hicks, LG, Zalpuski, M, Pelley, R. J, Chan, KK, and  Kraut, EH. A phase II study of chloroquinoxaline sulfonamide (CQS) in patients with metastatic colorectal carcinoma (MCRC). Invest New Drugs 24(4):343-346, 2006.

 

Zhang, Y, Hua, Y, Benbrook, D, Covey, JM, Dai, G, Liu, Z, and Chan, KK.  High Performance Liquid Chromatographic Analysis and Preclinical Pharmacokinetics of the Heteroarotinoid Antitumor Agent, SHetA2.  Cancer Chemother  Pharmacol. 58(5):561-569, 2006.

 

*Liu, Z, Marcucci, G, Byrd, JC, Grever, M, Xiao, J, and Chan, KK. Characterization of Decomposition Products and Preclinical and Low Dose Clinical Pharmacokinetics of Decitabine (5-aza-2’-deoxycytidine) by a New Liquid Chromatography Tandem Mass Spectrometry Quantification Method. Rapid Comm Mass Spectrom, 20(7):1117-1126, 2006.

 

Wei, X, Dai, G, Marcucci, G, Liu, Z, Hoyt, D, Blum, W, and Chan, KK. A Specific Picomolar Hybridization-based ELISA Assay for the Determination of Phosphorothioate Oligonucleotides in Plasma and Cellular Matrices. Pharm Res, 23(6):1251-1264, 2006.

 

O’Connor, OA, Smith, EA, Toner, LE, Teruya-Feldstein, J, Frankel, S, Rolfe, M, Wei, X, Liu, S, Marcucci, G, Chan, KK, and Chanan-Khan, A. The Combination of the Proteasome Inhibitor Bortezomib and the Bcl-2 Antisense Molecule Oblimersen Sensitizes Human B-Cell Lymphomas to Cyclophosphamide. Clin Cancer Res, 12(9): 2902-2911, 2006.

 

Shah, MH, Binkley, P, Chan, KK, Xiao, J, Arbogast, D, Collamore, M, Farra, Y, Young, D, Wright, J, and Grever, M. Cardiotoxicity of Histone Deacetylase Inhibitor Depsipeptide in Patients with Metastic Neuroendocrine Tumors. Clin Cancer Res, 12(13): 3997-4003, 2006.

 

Stram, DO, Yuan, J-M, Chan, KK, Gao, Y-T, Ross, RK, Yu, MC.  Beta-cryptoxanthin and Lung Cancer in Shanghai, China -an Examination of Potential Confounding with Cigarette Smoking Using Urinary Cotinine as a Biomarker of True Tobacco Exposure.  Nutrition and Cancer, 57(2): 123-129, 2006.

 

*Perera, M, Yin, D, Wu, D, Chan, KK, Miller, D, and Dalton,  JT.  In Vivo Metabolism and Final Disposition of a Novel Nonsteroidal Androgen in Rats and Dogs.  Drug Metabolism and Disposition, 34(10): 1713-1721, 2006.

 

Fang, L, Zhang, G, Zhang, Li, C, Zheng, X, Zhu, L, Xiao, JJ, Szakacs, G, Nadas, J, Chan, KK, Wang PG, and Sun, D.  Discovery of a Daunorubicin Analogue that Exhibits Potent Antitumor Activity and Overcomes P-gp-mediated drug resistance. J Med Chem 49(3): 932-941, 2006.

 

Fang, L, Battisti, RF, Cheng, H, Reigan, P, Xin, Y, Shen, J, Ross, D, Chan, KK, Martin, EW, Wang, PG, and Sun, D.  Enzyme Specific Activation of Benzoquinone Ansamycin Prodrugs Using HuCC49∆CH2-β-Galactosidase Conjugates.  J Med Chem 49(21): 6290-   6297, 2006.

 

Fang, L, Nicholas, HG, Holford, MB, Hinkle, G, Cao, X, Xiao, JJ, Bloomston, MP, Gibbs, S, Al Saif, OH, Dalton, JT, Chan, KK, Schlom, J, Martin, E, and Sun, D. Population Pharmacokinetics of Humanized Monoclonal Antibody HuCC49∆CH2 and Murine Antibody CC49 in Colorectal Cancer Patients. J Clin Pharmacol, 47(2): 227-237, 2007.

 

*Wei, X, Dai, G, Liu, Z, Cheng, H, Xie, Z, Marcucci, G, Chan, KK.  Metabolism of GTI-2040, a Phosphorothioate Oligonucleotide Antisense, Using Ion-pair Reversed Phase High Performance Liquid Chromatography (HPLC) Coupled with Electrospray Ion-trap Mass Spectrometry.  AAPSJ, 8(4) article 84, 2006.  (Invited manuscript)

 

*Cheng, H, Liu, Z, Blum, W, Byrd, J, Klisovic, R, Grever, MR, Marcucci, G, Chan, KK.  Quantification of Valproic Acid and its Metabolite 2-propyl-4-pentenoic Acid in Human Plasma Using HPLC-MS/MS. J Chrom B, doi:  10.1016/j. chromb.2006.11.027, 850(1-2):206-212, 2007.

 

Colitz, CMH, Latimer, FG, Cheng, H, Chan, KK, Reed, S, and Pennick, GJ.  Pharmacokinetics of Voriconazole Following Intravenous and Oral Administration and Body Fluid Concentrations of Voriconazole Following Repeated Oral Administration in Horses.  Amer Journal of Vet Res, 68(10): 1115-1121, 2007.

 

*Blum, W, Klisovic, RB, Hackanson, B, Liu, Z, Liu, S, Devine, H, Vukosavljevic, T, Huynh, L, Lozanski, G, Kefauver, C, Plass, C, Devine, SM, Heerema, NA, Murgo, A, Chan,  KK, Grever, MR, Byrd, JC, and Marcucci, G.  Phase 1 Study of Decitabine Alone or in Combination with Valproic Acid in Acute Myeloid Leukemia.  Journal of Clinical Oncology, 10.1200/JCO.2006.009.4169, 25(25):3884-3891, 2007.

 

*Liu, Z, Xie, Z, Liu, S, Blum, W, Perrotti, D, Paschka, P, Klisovic, R, Byrd, JC, Chan, KK, and Marcucci, G.  Characterization of In-Vitro and In-Vivo Hypomethylating Effect of Decitabine in Acute Myeloid Leukemia by a Rapid, Specific and Sensitive LC-MS/MS Method.  Nucleic Acid Research, 35(5) e31 doi:10.1093/nar/gkl1156, 2007.

 

*Liu, Z, Fan-Havard, P, Xie, Z, Ren, C, and Chan, KK.  A Liquid Chromatography/atmospheric Pressure Ionization Tandem Mass Spectrometry Quantitation Method for Nevirapine and its Two Oxidative Metabolites, 2-hydroxynevirapine and Nevirapine 4-carboxylic Acid, and Pharmacokinetics in Baboons.  Rapid Communications in Mass Spectrometry, 21(16): 2734-2742, 2007.

 

Liu, S, Klisovic, RB, Vukosavljevic, T, Yu, J, Paschka, P, Huynh, L, Pang, J, Neviani, P, Liu, Z, Blum, W, Chan, KK, Perrotti, D and Marcucci, G.  Targeting AML1/ETO-HDAC Repressor Complex:  A Novel Mechanism of Valproic Acid Mediated Gene Expression and Cellular Differentiation in AML1/ETO-positive Acute Myeloid Leukemia Cells.  JPET published on-line, Fast Forward, DOI: 10.1124/jpet.106.118406 , J Pharmacol Exp Thera, 321(3):953-960, 2007.

 

Fabbri, M, Garzon, R, Cimmino, A, Liu, Z, Zanesi, N, Callegari, E, Liu, S, Alder, H, Costinean, S, Fernandez-Cymering, C, Volinia, S, Guler, G, Morrison, CD, Chan, KK, Marcucci, G, Calin, GA, Huebner, K, and Croce, CM.  MicroRNA-29 Family Reverts Aberrant Methylation in Lung Cancer by Targeting DNA Methyltransferases 3A and 3B.  PNAS, 104(40) 15805-15810, 2007.

 

Liu, S, Liu, Z, Xie, Z, Pang, J, Yu, J, Lehmann, E, Huynh, L, Vukosavljevic, T, Takeki, M, Klisovic, RB, Baiocchi, RA, Blum, W, Porcu, P, Garzon, R, Byrd, JC, Perrotti, D, Caligiuri, MA,  Chan, KK, Wu, L-C, and Marcucci, G.  Bortezomib Induces DNA Hypomethylation and Silenced Gene Transcription by Interfering with Sp1/NF-kB-dependent DNA Methylatransferase Activity in Acute Myeloid Leukemia.  Blood, prepublished on-line DOI 10.1182/blood-2007-08-110171, 111(4):2364-2373, 2008.

 

Bekaii-Saab, TS, Liu, J, Chan, KK, Balcerzak, SP, Ivy, PS, Grever, MR, and Kraut, EH.  A Phase I and Pharmacokinetic Study of Weekly Oxaliplatin Followed by Paclitaxel in Patients with Solid Tumors.  Clin Cancer Res, 14(11): 3434-3440, 2008.

 

Klisovic, RB, Blum, W, Wei, X, Liu, S, Liu, Z, Xie, Z, Vukosavljevic, T, Kefauver, C, Huynh, L, Pang, J, Zweibel, JA, Devine, S, Byrd, JC, Grever, MR, Chan, K, and Marcucci, G.  Phase 1 Study of GTI-2040, an Antisense to Ribonucleotide Reductase, in Combination with High-Dose Cytarabine in Patients with Acute Myeloid Leukemia.  Clin Cancer Res, 14(12):  3889-3895. 2008.

 

Wei, X, Dai, G, Liu, Z, Cheng, H, Xie, X, Klisovic, R, Marcucci, G, and Chan, KK. Enzyme Kinetics of GTI-2040, a Phosphorothioate Oligonucleotide Targeting Ribonucleotide Reductase.  Drug Metabolism and Disposition, 36(11);2227-2233, 2008.  doi: 10.1124/dmd.108.021295. Fast-forward Published on-line, July 24, 2008.

 

Yuan, J-M, Chan, KK, Coetzee, GA, Castelao, JE, Watson, MA, Bell, DA, Wang, R, and Yu, MC.  Genetic determinants in the Metabolism of Bladder Carcinogens in Relation to Risk of Bladder Cancer.  Carcinogenesis, 29(7):  1386-1393, 2008. 

 

Yang, X, Koh, CG, Liu, S, Pan, X, Santhanam, R, Yu, B, Peng, Y, Pang, J, Golan, S, Talmon, Y, Jin, Y, Muthusamy, N, Byrd, JC, Chan, KK, Lee, LJ, Marcucci, G, and Lee, RJ.  Transferrin Receptor-Targeted Lipid Nanoparticles for Delivery of an Antisense Oligodeoxyribonucleotide against Bcl-2.  Molecular Pharmaceutics, 6(1):221-230, 2008.

 

*Liu, Z, Zhang, Y, Hua YF, Covey JM, Benbrook DM, and Chan KK.  Metabolism of a sulfur-containing heteroarotionoid antitumor agent, SHetA2, using liquid chromatography/tandem mass spectrometry.  Rapid Communications in Mass Spectrometry, 22: 3371-3381, 2008.

 

Liu, Z, Xie, Z, Jones, W, Pavlovicz, RE, Liu, S, Yu, J, Li, P-k, Liu, J, Fuchs, JR, Marcucci, G, Li, C, and Chan, KK.  Curcumin is a Potent DNA Hypomethylation Agent.  Bioorganic & Medicinal Chemistry Letters, 19:706-709, 2009.

 

Garzon, R, Liu, S, Fabbri, M, Liu, Z, Heaphy, CEA, Callegari, E, Schwind, S, Pang, J, Yu, J, Muthusamy, N, Volinia, S, Blum, W, Rush, LJ, Perrotti, D, Andreeff, M, Bloomfield, CD, Byrd, JC, Chan, K, Wu, L-C, Croce, CM, and Marcucci, G.  MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene re-expression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1.  Blood, doi:10.1182/blood-2008-07-170589, pre-published online February 11, 2009.

 

Liu, Z, Liu, S, Xie, Z, Pavlovics, RE, Wu, J, Chen, P, Aimiuwu, J, Pang, J, Bhasin, D, Neviani, P, Fuchs, JR, Plass, C, Li, P-K, Li, C, Huang, T-M, Wu, L-C, Rush, L, Wang, H, Perrotti, D, Marcucci, G, and Chan, KK.  DNA Methylation Modulation by a Sesquiterpene Lactone Parthenolide.  Journal of Pharmaceutical and Experimental Therapeutics, doi:10.1124/jpet.108.147934.  Fast-forward Published on-line, February 6, 2009.

 

*Chen, P, Liu, Z, Liu, S, Xie, X, Aimiuwu, J, Pang, J, Klisovic, R, Blum, W, Grever, MR, Marcucci, G, and Chan, KK.  A LC-MS/MS method for the analysis of intracellular nucleoside triphosphate levels.  Pharm Res, in press, February 2009.

 

 

 

 

Josephine Aimiuwu, B.S.

Ping Chen, Ph.D.

Ming Chiu, Ph.D.

Yonghua Ling, Ph.D.

Zhongfa Liu, Ph.D.

Vijay Sarathi, Ph.D.

Joy Scott, B.S. 

Hongyan Wang, M.D., Ph.D.

Zhiliang (Leon) Xie, M.D.

Xiaodong (Donald) Yin, M.S.