In conjunction with the NCI Contract N01-CM-52205, we collaborated with Dr. James Doroshow at the National Cancer Institute [(Laboratory of Human Toxicology & Pharmacology (LHTP), DTP, DCTD, NCI)] and Dr. Edward Newman, City of Hope National Cancer Center on the evaluation of the global DNA methylation effect assessment of the 5-fluoro-2'-deoxycytidine (FdC; NSC 48006) in the absence and presence of tetrahydrouridine. we have found DNA incorporation of FdC and a meeting abstract was presented (Liu, et al., Proc. AACR, April 2009, Denver, CO.
We have continued a long-term collaboration with Dr. Mimi C. Yu (University of Minnesota), and Dr. Ronald K. Ross (University of Southern California Norris Comprehensive Cancer Center) on projects relating to exposure of carcinogens, cigarette smoking, genetic determinants, and bladder cancer risk, which resulted in a number of publications as shown below (only showing since 2004).
- 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.
- 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.
- 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.
We have collaborated with Dr. Yogen Saunthararajah, Cleveland Clinic Taussig Cancer Institute, Cleveland Clinic Foundation, on a project entitled “Malignant stem-cell specific differentiation therapy.” This has resulted in a recently funded grant from the U.S. Department of Defense and the portion of the project is subcontracted to our laboratory. We will measure decitabine pharmacokinetics and the intracellular decitabine triphosphate levels in cell lines and other relevant tissues. The pharmacokinetic data and intracellular are to be correlated with the DMNT1 depletion and other relevant biomarkers.
We are also supporting two clinical trials conducted at multiple institutions. Recent abstracts of these are indicated below:
- Mitch A. Phelps, Danxin Wang, Josephine E. Aimiuwu, Sherri L. Starrett, Audrey C. Papp, Ahmed A. Ghany, William J. Hicks, Kavitha V. Kosuri, Gregory A. Otterson, Mark A. Socinski, Thomas E. Stinchcombe, Weiqiang Zhao, Larry J. Schaaf, Sanford H. Barsky, Kenneth K. Chan, Wolfgang Sadee, Miguel A. Villalona-Calero. Erlotinib in African Americans with lung cancer: a prospective, clinical, molecular, pharmacokinetic and pharmacogenetic characterization. AACR, Denver, CO. 2009.
- Tanios Bekaii-Saab, Mitch Phelps, Xiaobai Li, Motoyasu Saji, Kavitha Kosuri, Laura Goff, John Kauh, Bert O’Neil, Christopher South, James Thomas, Stephanie Balsom , Nicole Chattah, Catherine Balint, Ryan Liersemann, Vasily Vasko, William Marsh, L. Austin Doyle, Matthew Ringel, Miguel Villalona Calero. A Multi-institutional Study of AZD6244 in Patients with Advanced Biliary Cancers. AACR, Denver, CO. 2009.