Neuroblastoma, DOPA

Since dopamine is present in sympathetic nervous tissue as a precursor of norepinephrine, and it has a separate metabolic pathway that yields homovanillic acid (HVA), tumors such as neuroblastomas may cause elevations of the urinary dopamine and its metabolite HVA. In some cases these elevations have been observed with normal VMA, total catecholamine, and metanephrine. Urinary HVA is usually normal in patients with phenochromocytoma. Increased HVA is found in special fluids of patients with Parkinson s disease treated with L-dopa. 

Seitz G, Gebhardt S, Beck JF, Bohm W, Lode HN, Niethammer D, and Bruchelt G (1998) Ascorbic acid stimulates DOPA synthesis and tyrosine hydroxylase gene expression in the human neuroblastoma cell line SK-N-SH. Neuroscience Letters 244,33-6. 

Additional markers of catecholamine overproduction have been employed to improve the biochemical detection of neuroblastomas. Free dopamine may be abnormal in urine from neuroblastoma patients with VMA and HVA excretion. Combined testing for VMA, HVA, and dopamine may therefore improve tumor detection, and in 1993 an international consensus report on neuroblastoma diagnosis added dopamine to the Hst of acceptable measurements to document the adrenergic nature of the tumor. Plasma measurements of dopamine and L-dopa, the amino acid precursor of dopamine, may also have clinical value and allow the alternate use of plasma. Measurement of methylated metabolites, especially normetanephrine, has also been explored. When urinary normetanephrine, metanephrine, methoxytyra-mine, dopamine, norepinephrine, VMA, and HVA were measured, clinical sensitivity for detection of neuroblastomas was 97% to 100% when results of normetanephrine testing were coupled either with VMA in the infants or with HVA in children greater than age 1. Even with an extended panel of catecholamines and metabolite measurements, a low incidence of nonsecreting tumors continues to be identified and should be considered in the interpretation of a negative test result. 

Eldrup E, Clausen N, Scherling B, Schmiegelow R. Evaluation of plasma 3,4-dihydroxyphenylacetic acid (DOPAC) and plasma 3,4-dihydroxyphenyialanine (DOPA) as tumor markers in children with neuroblastoma. Scand J Clin Lab Invest 2001 61 479-90. 

Goldstein DS, Stull R, Eisenhofer G, Sisson JC, Weder A, Averbuch SD, Reiser HR. Plasma 3,4-dihydrox-yphenylalanine (dopa) and catecholamines in neuroblastoma or pheochromocytoma. Ann Intern Med 1986 105 887-8. 

Kelson L, Johnson GA, Smith R. DOPA metabolism in neuroblastoma. Med Pediatr Oncol 1980 8 317-22. 

An interesting finding about patients with neuroblastoma has been obtained by von Studnitz (S39). This author found in two of six such patients an increase in the urinary metabolites of DOPA besides dopamine and 3-methoxy-4-hydroxyphenylalanine, 3,4-dihydroxyphenylacetic (homoprotocatechuic) acid, which is not found in normal urine, occurred in the mine of these patients, whereas the elimination of homovanillic acid was increased. 

Related to the tunichromes are halocyamines A (41) and B (42) from Halocynthia roretzi. [39]. These are tetrapeptides which contain a Dopa residue (note the authors have depicted a D-Dopa residue in their structure). Both halocyamines displayed antimicrobial activity against B. subtilis (MIC 50pg /mL), B. megateruine (MIC 50 pg/mL), B. cereus (MIC 100 pg /mL) and the yeast Cryptococcus neoformans (MIC 100 pg /mL). Halocyamine A was also found to be cytotoxic to neuroblastoma N-18 cells at 160 pM for 24 hours. It caused degeneration of neurite and soma in cultured rat fetal brain cells at 100 pM and death of Hep-G2 cells at 200 pM for 24 hours. 

In addition, iV-acetyldopamine, which was found in the urine of a phaeochromocytoma patient as well as a neuroblastoma patient, 7) s shown to have an inhibitory effect on dopa-decarboxylase during in vitro experi-... 

---