Kogner P, Barbany G, Persson H, Söderhäll S, Ahström L, Björk O
Department of Pediatrics, Karolinska Hospital, Stockholm, Sweden.
Prog Clin Biol Res. 1994;385:147-53.
Four children with advanced or relapsed neuroblastoma were treated with oral 13-cis-retinoic acid 0.75 mg/kg/day. Clinical response to retinoic acid was noted only in the two children with tumors coexpressing trk protooncogene mRNA, encoding an essential part of the nerve growth factor (NGF) high affinity receptor, and low affinity NGF receptor gene (LNGFR) mRNA. Clinical stage or age, plasma neuropeptide Y, tumor DNA ploidy and N-myc amplification did not as accurately predict response to retinoic acid as NGF receptor mRNAs. In vitro data have shown that retinoic acid up regulates LNGFR expression and NGF sensitivity via interaction with specific regulatory elements in the LNGFR gene promoter. We hypothesize that part of the therapeutic effect of retinoic acid in neuroblastoma in vivo may be exerted via increased NGF receptor expression and NGF sensitivity. Analysis of trk and LNGFR mRNA may be useful to predict clinical response to retinoic acid in these children.
4名患有晚期或复发性神经母细胞瘤的儿童接受了口服13-顺式维甲酸治疗，剂量为0.75毫克/千克/天。仅在2名肿瘤同时表达trk原癌基因mRNA（其编码神经生长因子（NGF）高亲和力受体的重要部分）和低亲和力NGF受体基因（LNGFR）mRNA的儿童中观察到了对维甲酸的临床反应。临床分期或年龄、血浆神经肽Y、肿瘤DNA倍体和N-myc扩增对维甲酸反应的预测准确性不如NGF受体mRNA。体外数据表明，维甲酸通过与LNGFR基因启动子中的特定调控元件相互作用，上调LNGFR表达和NGF敏感性。我们推测，维甲酸在体内对神经母细胞瘤的部分治疗作用可能是通过增加NGF受体表达和NGF敏感性来实现的。分析trk和LNGFR mRNA可能有助于预测这些儿童对维甲酸的临床反应。
