Schengrund C L, Shochat S J
Department of Biological Chemistry, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, PA 17033.
Neurochem Pathol. 1988 Jun;8(3):189-202. doi: 10.1007/BF03160146.
Neuroblastomas from children presenting with tumors at various ages and different primary sites (abdominal, adrenals, pelvic, and thoracic) were studied. Analysis of the ganglioside patterns of 53 tumors indicated that patients who were either disease positive 2 yr following surgery or dead of disease, had significantly (p less than 0.005) less GT1b plus GD1b than tumors from patients that were disease free 2 yr post surgery. The presence of GD2 in 45 of the tumors correlates well with the suggestion that it can be used as a marker in neuroblastoma diagnosis. Children with thoracic neuroblastomas have a significantly better prognosis than children with tumors in other anatomic sites. Analysis of the ganglioside composition of these tumors only, indicated that they had a significantly higher (p less than 0.005) concentration of GT1b and GD1b and a significantly lower concentration (p less than 0.025) of monosialogangliosides than those patients who were dead of disease or had persistent disease. These results suggest that low levels of GT1b and GD1b correlate with a poor prognosis. The thoracic neuroblastomas may be comprised of more "differentiated" neuroblastoma cells (ganglioside patterns more similar to the CNS), and this may contribute to the fact that about 85% of children with thoracic neuroblastoma recover. To understand why the ganglioside pattern may serve as a prognostic indicator for neuroblastoma, it is necessary to know whether gangliosides have specific roles in neuronal differentiation. Our approach to this question is to compare the effect(s) of added ganglioside or the corresponding oligosaccharide on neuroblastoma cells. Results obtained suggest that the oligosaccharide from GM1 is able to enhance neuritogenesis by S20Y murine neuroblastoma cells to the same extent that GM1 does.
对来自不同年龄和不同原发部位(腹部、肾上腺、盆腔和胸部)出现肿瘤的儿童神经母细胞瘤进行了研究。对53个肿瘤的神经节苷脂模式分析表明,术后2年疾病呈阳性或死于疾病的患者,其GT1b加GD1b明显(p<0.005)少于术后2年无疾病患者的肿瘤。45个肿瘤中GD2的存在与它可作为神经母细胞瘤诊断标志物的观点密切相关。患有胸段神经母细胞瘤的儿童预后明显好于其他解剖部位患有肿瘤的儿童。仅对这些肿瘤的神经节苷脂组成进行分析表明,与死于疾病或患有持续性疾病的患者相比,它们的GT1b和GD1b浓度明显更高(p<0.005),单唾液酸神经节苷脂浓度明显更低(p<0.025)。这些结果表明,GT1b和GD1b水平低与预后不良相关。胸段神经母细胞瘤可能由更多“分化”的神经母细胞瘤细胞组成(神经节苷脂模式更类似于中枢神经系统),这可能是约85%的胸段神经母细胞瘤患儿康复的原因。为了解神经节苷脂模式为何可作为神经母细胞瘤的预后指标,有必要了解神经节苷脂在神经元分化中是否具有特定作用。我们解决这个问题的方法是比较添加神经节苷脂或相应寡糖对神经母细胞瘤细胞的影响。获得的结果表明,GM1的寡糖能够与GM1一样程度地增强S20Y小鼠神经母细胞瘤细胞的神经突形成。