LaBrosse E H, Comoy E, Bohuon C, Zucker J M, Schweisguth O
J Natl Cancer Inst. 1976 Sep;57(3):633-8. doi: 10.1093/jnci/57.3.633.
Previous studies indicating the importance of catecholamine metabolism in neuroblastoma were briefly reviewed. Metabolic pathways were presented showing how the major urinary metabolites 3-methoxy-4-hydroxymandelic acid (VMA) and 3-methoxy-4-hydroxy-phenylacetic acid (HVA) are formed from norepinephrine and from dopamine plus 3,4-dihydroxyphenylalanine (DOPA), respectively. For 289 neuroblastoma patients at the time of diagnosis, the urinary excretion of VMA was significantly elevated in 75%, and HVA was elevated in 80%. Periodic assay of these metabolites during the course of the disease revealed that the excretion trends were of prognostic value with 80-90% reliability. By contrast, when the excretion in only the initial urine specimens was considered, the survival rate was the same for patients with normal, and with significantly elevated, excretion. Review of the results of tracer studies aimed at elucidating the in vivo metabolic origins of the urinary metabolites suggested that a) in neuroblastoma, the catecholamines were largely inactivated by intracellular metabolism in the tumor cells; b) there was excess production and excretion of the norepinephrine precursors, DOPA and dopamine; and c) in the tumors of most neuroblastoma patients, the initial enzyme in catecholamine synthesis, tyrosine hydroxylase, had an activity comparable with that in normal adrenal glands. The importance of the metabolism of catecholamines in patients with neuroblastoma was stressed: a) The excretion of elevated levels of urinary catecholamine metabolites were useful in diagnosis and in following the course of the disease, and b) study of the catecholamine metabolism in these patients permitted examination of possible relationships between the activity of the enzymes involved in catecholamine synthesis and the malignancy of this tumor.
先前表明儿茶酚胺代谢在神经母细胞瘤中重要性的研究已作简要综述。文中展示了代谢途径，说明了主要尿代谢产物3 - 甲氧基 - 4 - 羟基扁桃酸（VMA）和3 - 甲氧基 - 4 - 羟基苯乙酸（HVA）分别是如何由去甲肾上腺素以及多巴胺加3,4 - 二羟基苯丙氨酸（DOPA）形成的。对于289例神经母细胞瘤患者，在诊断时，75%的患者尿中VMA排泄显著升高，80%的患者HVA排泄升高。在疾病过程中对这些代谢产物进行定期检测发现，排泄趋势具有预后价值，可靠性为80 - 90%。相比之下，若仅考虑初始尿液标本中的排泄情况，排泄正常和排泄显著升高的患者生存率相同。对旨在阐明尿代谢产物体内代谢起源的示踪研究结果进行综述表明：a）在神经母细胞瘤中，儿茶酚胺主要在肿瘤细胞内通过细胞内代谢失活；b）去甲肾上腺素前体DOPA和多巴胺产生和排泄过量；c）在大多数神经母细胞瘤患者的肿瘤中，儿茶酚胺合成的初始酶酪氨酸羟化酶的活性与正常肾上腺中的活性相当。强调了儿茶酚胺代谢在神经母细胞瘤患者中的重要性：a）尿中儿茶酚胺代谢产物水平升高对诊断和疾病进程监测有用；b）对这些患者儿茶酚胺代谢的研究有助于检查儿茶酚胺合成相关酶的活性与该肿瘤恶性程度之间可能存在的关系。
