THERAPEUTIC ROLE OF FERRITIN IN NEUROBLASTOMA

铁蛋白是一种铁储存蛋白，存在于正常人体内， 血清的 高于正常血清水平，发现在一些 神经母细胞瘤患者，并预测预后不良。 间接 有证据表明，这些患者的铁蛋白可能是 由肿瘤细胞合成。 为了了解为什么 铁蛋白水平与预后相关，研究集中在 铁蛋白抑制宿主免疫应答的能力， 从而增强肿瘤生长。 据推测，除了 这些作用，铁蛋白或其携带的铁离子可能 作为神经母细胞瘤的生长因子， 有助于肿瘤生长。 作为一种假设， 铁的螯合可以提供一种治疗 神经母细胞瘤 初步数据表明，去铁胺， 高亲和力铁螯合剂，可从铁蛋白中提取铁， 杀死体外生长的神经母细胞瘤细胞。 进一步开拓 铁蛋白在神经母细胞瘤中的生物学作用以及 去铁胺杀死神经母细胞瘤细胞的机制， 建议：建立神经母细胞瘤细胞可以合成 铁蛋白;以确定铁蛋白是否增强核酸或 神经母细胞瘤细胞在无血清培养基中的蛋白质合成; 并研究神经母细胞瘤细胞结合铁蛋白的能力， 已知的生长因子的方式。 此外， 去铁胺对肿瘤细胞系的DNA、RNA和 蛋白质合成、细胞周期和铁依赖性 将研究细胞酶。 最后，利用现有的 毒性数据，儿童去铁胺II期临床试验 终末期神经母细胞瘤和其他恶性肿瘤的患者， 进行。

Ferritin is an iron-storage protein that is found in normal human serum. Greater than normal serum levels are found in some patients with neuroblastoma and predict a poor outcome. Indirect evidence suggests that ferritin in these patients may be synthesized by their tumor cells. In an attempt to understand why ferritin levels correlate with prognosis, studies have focused on the ability of ferritin to inhibit host immune responses and thereby enhance tumor growth. It is postulated that in addition to these effects, ferritin or the ferric ions that it carries may function as a growth factor for neuroblastoma and directly contribute to tumor growth. As a correlary it is postulated that chelation of iron may provide an approach to the treatment of neuroblastoma. Preliminary data suggest that desferoxamine, a high affinity iron chelator which can extract iron from ferritin, kills growing neuroblastoma cells in vitro. To further explore the biological role of ferritin in neuroblastoma as well as the mechanism by which desferoxamine kills neuroblastoma cells, it is proposed: to establish that neuroblastoma cells can synthesize ferritin; to determine whether ferritin potentiates nucleic acid or protein synthesis by neuroblastoma cells in serum-free medium; and to study the ability of neuroblastoma cells to bind ferritin in the manner of known growth factors. In addition the effect of desferoxamine on tumor cell lines with respect to DNA, RNA and protein synthesis, cell cycling, and activity of iron-dependent cellular enzymes will be studied. Finally, utilizing available toxicity data, a phase II clinical trial of desferoxamine in children with end-stage neuroblastoma and other malignancies will be conducted.