THERAPEUTIC ROLE OF FERRITIN IN NEUROBLASTOMA

铁蛋白是一种储存铁的蛋白质，存在于正常人体内 血清。一些患者的血清水平高于正常水平 患者患有神经母细胞瘤，并预测预后不佳。间接法 有证据表明，这些患者体内的铁蛋白可能是 由他们的肿瘤细胞合成。试图理解为什么 铁蛋白水平与预后相关，研究重点放在 铁蛋白抑制宿主免疫反应的能力和 从而促进肿瘤生长。据推测，除了 这些效应，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，并直接 有助于肿瘤的生长。作为推论，我们假定 铁的螯合作用可能提供一种治疗糖尿病的方法。 神经母细胞瘤。初步数据表明，去铁胺是一种 可以从铁蛋白中提取铁的高亲和力铁络合剂， 在体外杀死生长的神经母细胞瘤细胞。为了进一步探索 铁蛋白在神经母细胞瘤中的生物学作用 去铁胺杀死神经母细胞瘤细胞的机制，它是 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条件下的蛋白质合成； 并研究神经母细胞瘤细胞与铁蛋白结合的能力 已知的生长因子的方式。此外， 去铁胺对肿瘤细胞DNA、RNA和DNA的影响 蛋白质合成、细胞周期和铁依赖的活性 将研究细胞酶。最后，利用可用的 儿童去铁胺II期临床试验的毒性数据 与终末期神经母细胞瘤和其他恶性肿瘤 指挥。

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.