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神经母细胞瘤和神经节神经瘤中的生长抑素和血管活性肠肽(VIP):色谱特征及手术过程中的释放情况

Somatostatin and vasoactive intestinal peptide (VIP) in neuroblastoma and ganglioneuroma: chromatographic characterisation and release during surgery.

作者信息

Bjellerup P, Theodorsson E, Kogner P

机构信息

Department of Clinical Chemistry, Karolinska Hospital, Stockholm, Sweden.

出版信息

Eur J Cancer. 1995;31A(4):481-5. doi: 10.1016/0959-8049(95)00074-s.

Abstract

Neuroblastomas and ganglioneuromas frequently produce somatostatin (SOM) and vasoactive intestinal peptide (VIP), and elevated concentrations in tumour tissue are associated with favourable outcome. Both somatostatin and VIP have been shown to have an autocrine effect on tumour growth and differentiation in vitro, and VIP may cause clinical symptoms when released systemically. Using gel-permeation chromatography and specific radioimmunoassays, we further characterised somatostatin-like immunoreactivity (SOM-LI) and VIP-like immunoreactivity (VIP-LI) in neuroblastoma and ganglioneuroma tumour tissue. The major part of SOM-LI and VIP-LI in both neuroblastoma and ganglioneuroma represents the biologically active forms SOM-28, SOM-14 and VIP-2, respectively. 21 children with neuroblastoma and ganglioneuroma were monitored with serial plasma samples during surgery. In 8 children with measurable concentrations of SOM-LI, all showed increased concentrations during tumour manipulation (P = 0.004) that subsequently decreased below preoperative levels in all but one case (P = 0.06). The only child presenting with diarrhoea showed the highest preoperative plasma VIP-LI in the study (54 pmol/l). 2 children with increased concentrations of VIP-LI preoperatively showed a rapid decrease after surgical tumour removal. These findings indicate a systemic release from the tumours. It is concluded that plasma and tumour tissue from children with neuroblastoma and ganglioneuroma contain biologically active molecular forms of somatostatin and vasoactive intestinal peptide. These peptides may bear significance both for specific symptoms in certain patients as well as influencing tumour growth and differentiation in vivo.

摘要

神经母细胞瘤和神经节神经瘤经常产生生长抑素(SOM)和血管活性肠肽(VIP),肿瘤组织中浓度升高与良好预后相关。生长抑素和VIP在体外均已显示对肿瘤生长和分化具有自分泌作用,并且当全身释放时,VIP可能会引起临床症状。我们使用凝胶渗透色谱法和特异性放射免疫测定法,进一步对神经母细胞瘤和神经节神经瘤肿瘤组织中的生长抑素样免疫反应性(SOM-LI)和血管活性肠肽样免疫反应性(VIP-LI)进行了表征。神经母细胞瘤和神经节神经瘤中SOM-LI和VIP-LI的主要部分分别代表生物活性形式的SOM-28、SOM-14和VIP-2。在手术期间,对21例患有神经母细胞瘤和神经节神经瘤的儿童进行了连续血浆样本监测。在8例可测量SOM-LI浓度的儿童中,所有儿童在肿瘤操作期间浓度均升高(P = 0.004),除1例之外,所有儿童随后均降至术前水平以下(P = 0.06)。在该研究中,唯一出现腹泻的儿童术前血浆VIP-LI最高(54 pmol/l)。2例术前VIP-LI浓度升高的儿童在手术切除肿瘤后迅速下降。这些发现表明肿瘤发生了全身释放。结论是,患有神经母细胞瘤和神经节神经瘤的儿童的血浆和肿瘤组织中含有生物活性分子形式的生长抑素和血管活性肠肽。这些肽对于某些患者的特定症状以及体内肿瘤生长和分化可能都具有重要意义。

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