Professor Department of Pharmacology Ph.D., Pharmacology Biosketch [.pdf]
State University of New York, Downstate Medical Center
Department of Pharmacology
- Drug resistance in cancer cells
One of the major obstacles to successful chemotherapeutic treatment of cancer is the emergence of drug-resistant cancer cells. To try to prevent drug-resistance, anticancer drugs are frequently used in combination. Research in this laboratory, however, has shown that in some instances the use of certain drug combinations actually enhances the frequency of drug-resistant cancer cells. Resistance in these cases comes about by gene amplification. For example, cancer cells become resistant to N-phosphonoacetyl-L-aspartate (PALA) by amplification of the gene that codes for the enzyme, aspartate transcarbamoylase, the target of PALA. Amplification of the gene leads to overproduction of the target enzyme and PALA-resistance. Pretreatment of cells with cytosine arabinoside (araC) increases the frequency of PALA-resistance. This laboratory is studying how the resistance occurs and how its frequency is enhanced by araC. The work is mainly with cultured cells and employs biochemical and molecular biological techniques.
- Goz, B., and Bastow, K.F. (1997) A possible role for topoisomerase II in cell death and N-phosphonoacetyl-L-aspartate-resistance frequency and its enhancement by 1--D-arabinofuranosyl cytosine and 5-fluoro-2'-deoxyuridine. Mut Res 38(2)4: 89-106. Abstract
- Chen, X., Bastow, K., Goz, B., Kucera, L., Morris-Natschke, S.L., and Ishaq, K.S. (1996) Synthesis, antitumor and antiviral activity of novel thymidine analogs. J Med Chem 39(17): 3412-7. Abstract
- Chen, X., Bastow, K., Goz, B., Kucera, L., Morris-Natschke, S.L., and Ishaq, K.S. (1996) Boronic acid derivatives targeting HIV-1. Antiviral Chem Chemother 7: 108-114.
- Goz, B., and Jeffs, L. (1994) The enhancement of the frequency of resistance to N-phosphonoacetyl-L-aspartate and methotrexate by 1--D-arabinofuranosylcytosine: The effect of dipyridamole. J Pharmacol Exptl Therap 270(2): 480-4. Abstract
- Chen, Y., Goz, B., and Kirkman, L. (1993) An analysis of vincristine-resistance in BHK cells pretreated with 1--D- arabinofuranosylcytosine. Anticancer Res 13(1): 249-55. Abstract