Graham-Pole J, Salmi T, Anton A H, Abramowsky C, Gross S
Cancer. 1983 Mar 1;51(5):834-9. doi: 10.1002/1097-0142(19830301)51:5<834::aid-cncr2820510515>3.0.co;2-#.
This study was undertaken to better define the relationship between catecholamine (CAT) metabolism within the malignant neuroblast and other factors known to influence clinical outcome in neuroblastoma (NB). Several CATs and their metabolites were measured in 32 tumors and 47 urines from 60 newly diagnosed children with neurogenic tumors. Absolute and relative CAT concentrations were correlated with age, clinical stage, histologic differentiation and survival duration. The major findings are: (1) urinary CAT excretion patterns often differ markedly from tumor CAT patterns in the same child, which may be explained by the continuous nature of tumor metabolism, hepatic and renal catabolism, and sampling errors; (2) definite patterns of biochemical maturation are apparent in tumors and urines, but standard light microscopy is insufficient to correlate this with degree of histologic differentiation; (3) more differentiated patterns of CAT metabolism, both in tumor and urine, are significantly associated with age less than 1 year at diagnosis, and with more favorable clinical Stage (I, II, IVS). Tumor NE was increased relative to DM and DA, and urine NMN and VMA were increased relative to DM and HVA, in these patients. (4) this more differentiated CAT pattern in infants and in less advanced stages was reflected in their better survival. Greater maturity of tumor enzyme systems is the probable reason for the better prognosis of NB in infants less than 1 year. Individual enzymes should be measured in fresh tumor tissues, and related to relative and absolute CAT concentrations in tumor and urine, to try to categorize patients on the basis of clearcut biological differences when planning new treatment strategies for NB.
本研究旨在更好地界定恶性神经母细胞瘤内儿茶酚胺(CAT)代谢与其他已知影响神经母细胞瘤(NB)临床结局的因素之间的关系。对60例新诊断的神经源性肿瘤患儿的32个肿瘤组织和47份尿液样本进行了几种CAT及其代谢产物的检测。将CAT的绝对浓度和相对浓度与年龄、临床分期、组织学分化程度和生存时间进行关联分析。主要研究结果如下:(1)同一患儿的尿CAT排泄模式往往与肿瘤CAT模式有显著差异,这可能是由于肿瘤代谢的持续性、肝脏和肾脏的分解代谢以及采样误差所致;(2)肿瘤组织和尿液中存在明确的生化成熟模式,但标准光学显微镜检查不足以将其与组织学分化程度相关联;(3)肿瘤组织和尿液中,CAT代谢模式越分化,与诊断时年龄小于1岁以及更有利的临床分期(I、II、IVS期)显著相关。在这些患者中,肿瘤去甲肾上腺素(NE)相对于多巴胺(DM)和多巴胺(DA)增加,尿液中烟酰胺单核苷酸(NMN)和香草扁桃酸(VMA)相对于DM和高香草酸(HVA)增加。(4)婴儿和较早期阶段中这种更分化的CAT模式反映在其更好的生存情况上。肿瘤酶系统更成熟可能是1岁以下婴儿NB预后较好的原因。在规划NB的新治疗策略时,应在新鲜肿瘤组织中检测个体酶,并将其与肿瘤组织和尿液中CAT的相对浓度和绝对浓度相关联,试图根据明确的生物学差异对患者进行分类。