Pharmacologic modulation of the physiologic and biochemical processes regulating MNB growth and differentiation will be systematically investigated in tissue culture and in situ tumor models. Emphasis will be placed upon the synthesis and pharmacologic evaluation of analogues directed against the naturally occurring and biologically important substrate, adenosine. The study will consist of four major components: 1. Evaluation of structure activity relationships between adenosine analogues and pharmacologic response. 2. Elucidation of the mechanism(s) and enzymatic sites of action of adenosine analogues. 3. The role of active membrane localized nucleoside transport systems and intracellular phosphorylation reactions as determinants of drug action. 4. The therapeutic application of adenosine analogues as selective inhibitors of MNB tumor cell growth in mixed cell populations containing bone marrow cells. Chemotherapeutic applications of transport-dependent cytotoxicity will be evaluated by determining their efficacy in purging neuroblastoma tumor cells from bone marrow cells.
| Hamre, M R; Clark, S H; Mirkin, B L (1995) Resistance to inhibitors of S-adenosyl-L-homocysteine hydrolase in C1300 murine neuroblastoma tumor cells is associated with increased methionine adenosyltransferase activity. Oncol Res 7:487-92 |
| Horn, P T; Mirkin, B L (1989) Lack of effect of the opioid antagonist, naltrexone, on the in situ growth of C-1300, N1E-115 and NS206 murine neuroblastoma tumor cell lines. Life Sci 45:2539-45 |
