The biological characteristics of the C-1300 murine neuroblastoma will be defined and an in vivo model developed to study the mechanisms of action of drugs that influence tumor viability and differentiation.
Specific aims of this proposal will be to clarify the regulatory role of macromolecular methyltransferases on cyclic nucleotide metabolism, establish longitudinal correlates between catecholamine metabolism and biosynthesis and tumor growth in vivo and to quantitate the effects and mechanisms of pharmocologic agents that modify methyltransferase activity or alter adrenergic neuronal function. The investigation will test the hypothesis that macromolecluar methylation systems function as molecular regulators of neuroblastoma growth and tumor differentiation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS017194-05
Application #
3397419
Study Section
Pathology A Study Section (PTHA)
Project Start
1981-04-01
Project End
1986-11-30
Budget Start
1985-04-01
Budget End
1986-11-30
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Fink, D W; Horn, P T; Mirkin, B L (1992) Differential effects of 6-hydroxydopamine-induced ablation of peripheral and central adrenergic axons on C-1300 murine neuroblastoma tumor growth and catecholamine concentration in the A/J mouse. J Pharmacol Exp Ther 262:1070-5
Bostrom, B; Hogenkamp, H P; Mirkin, B L (1988) Inhibitory effect of adenosine dialdehyde on in situ murine neuroblastoma growth. Cancer Res 48:5933-6
Tuchman, M; O'Dea, R F; Ramnaraine, M L et al. (1988) Pyrimidine base degradation in cultured murine C-1300 neuroblastoma cells and in situ tumors. J Clin Invest 81:425-30
Mirkin, B L; Fink Jr, D W; O'Dea, R F (1988) ""In situ"" modulation of murine neuroblastoma growth and biochemical differentiation by the adrenergic nervous system and nerve growth factor. Prog Clin Biol Res 271:317-26
Bostrom, B; Mirkin, B L (1988) Elevation of lumbar cerebrospinal fluid catecholamine metabolites in patients with cranial and/or intracranial metastatic neuroblastoma. Prog Clin Biol Res 271:557-64
Fink Jr, D W; Mirkin, B L (1987) Effects of chemical sympathectomy in neonatal and adult mice on C-1300 neuroblastoma tumor growth and catecholamine content. Cancer Res 47:5620-5
Bostrom, B; Mirkin, B L (1987) Elevation of cerebrospinal fluid catecholamine metabolites in patients with intracranial tumors of neuroectodermal origin. J Clin Oncol 5:1090-7
O'Dea, R F; Mirkin, B L; Hogenkamp, H P et al. (1987) Effect of adenosine analogues on protein carboxylmethyltransferase, S-adenosylhomocysteine hydrolase, and ribonucleotide reductase activity in murine neuroblastoma cells. Cancer Res 47:3656-61
Mirkin, B L; O'Dea, R F; Hogenkamp, H P (1987) Cytotoxic action of adenosine nucleoside and dialdehyde analogues on murine neuroblastoma in tissue culture: structure-activity relationships. Cancer Res 47:3650-5
Tuchman, M; Stoeckeler, J S; Kiang, D T et al. (1985) Familial pyrimidinemia and pyrimidinuria associated with severe fluorouracil toxicity. N Engl J Med 313:245-9

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