Investigation of the insulin-like growth factor-1 signaling pathway in localized Ewing sarcoma: a report from the Children's Oncology Group.
Investigation of the insulin-like growth factor-1 signaling pathway in localized Ewing sarcoma: a report from the Children's Oncology Group.
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对局部ewing肉瘤中胰岛素样生长因子1信号通路的研究：儿童肿瘤学组的报告。
DOI：
10.1002/cncr.26112
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发表时间：
2011-11-01
期刊：
影响因子：
6.2
通讯作者：
Toretsky JA
中科院分区：
文献类型：
--
作者：
Borinstein SC;Barkauskas DA;Krailo M;Scher D;Scher L;Schlottmann S;Kallakury B;Dickman PS;Pawel BR;West DC;Womer RB;Toretsky JA
胰岛素样生长因子-1 (IGF-1) 信号通路在尤文肉瘤 (ES) 的病理学中发挥着重要作用。回顾性研究表明 IGF-1 和 IGF 结合蛋白 3 (IGFBP-3) 的水平与 ES 患者的预后相关。在 269 名先前未经治疗的局限性 ES 患者中对 IGF-1 信号通路进行了前瞻性研究。诊断时获取血清样本，并通过酶联免疫吸附测定法测定 IGF-1 和 IGFBP-3 的浓度。此外，还进行了免疫组织化学 (IHC) 检测磷酸化 p70S6 激酶、蛋白激酶 B (Akt) 和叉头盒蛋白 O1 (FOXO1)，并确定蛋白酪氨酸磷酸酶-L1 (PTPL1) 的存在。 IHC 结果以及 IGF-1 和 IGFBP-3 浓度与年龄、肿瘤位置、性别、无事件生存期和总生存期相关。年龄 > 18 岁的患者往往具有较高水平的 IGF-1 (P =.10)、较低水平的 IGFBP-3 (P =.16) 以及较低的 IGFBP-3:IGF-1 比率 (P =.01)。未观察到性别、肿瘤位置或结果与 IGF-1 或 IGFBP-3 浓度之间的相关性。在大多数患者组织中检测到 p70S6 激酶、Akt 和 FOXO1 的磷酸化，但与年龄、性别或肿瘤位置无关。 PTPL1 存在于 >80% 的肿瘤中，并且与年龄、性别或肿瘤位置不相关。磷酸化 p70S6 激酶、磷酸化 FOXO1、磷酸化 Akt 或 PTPL1 的存在情况下，存活率没有差异。基线 IGFBP-3:IGF-1 比率与年龄相关，但不影响 ES 患者的预后。作者得出结论，对于 ES 患者，特别是接受 IGF-1 受体抗体抑制剂治疗的患者，有必要对 IGF-1 通路进行额外研究。
The insulin-like growth factor-1 (IGF-1) signaling pathway plays an important role in the pathology of Ewing sarcoma (ES). Retrospective studies have suggested that levels of IGF-1 and IGF binding protein 3 (IGFBP-3) are correlated with the outcome of patients with ES. The IGF-1 signaling pathway was investigated prospectively in 269 patients who had localized, previously untreated ES. Serum samples were obtained at diagnosis, and concentrations of IGF-1 and IGFBP-3 were determined by enzyme-linked immunosorbent assays. In addition, immunohistochemistry (IHC) was performed to assay for phosphorylated p70S6 kinase, protein kinase B (Akt), and forkhead box protein O1 (FOXO1) and to determine the presence of protein tyrosine phosphatase-L1 (PTPL1). IHC findings along with IGF-1 and IGFBP-3 concentrations were correlated with age, tumor location, sex, event-free survival, and overall survival. Patients aged >18 years tended to have higher levels of IGF-1 (P =.10), lower levels of IGFBP-3 (P =.16), and decreased IGFBP-3:IGF-1 ratios (P =.01). No correlations were observed between sex, tumor location, or outcomes and concentrations of IGF-1 or IGFBP-3. Phosphorylation of p70S6 kinase, Akt, and FOXO1 was detected in the majority of patient tissues but was not associated with age, sex, or tumor location. PTPL1 was present in >80% of tumors and also was not correlated with age, sex, or tumor location. There was no difference in survival with respect to the presence of phosphorylated p70S6 kinase, phosphorylated FOXO1, phosphorylated Akt, or PTPL1. The baseline IGFBP-3:IGF-1 ratio was correlated with age but did not affect the outcomes of patients with ES. The authors concluded that additional investigation of the IGF-1 pathway is warranted in patients with ES, and especially in those who have received treatment with IGF-1 receptor antibody inhibitors.
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影响因子：
3.2
作者：
Houghton, Peter J.;Morton, Christopher L.;Gorlick, Richard;Kolb, E. Anders;Keir, Stephen T.;Reynolds, C. Patrick;Kang, Min H.;Maris, John M.;Wu, Jianrong;Smith, Malcolm A.
通讯作者：
Smith, Malcolm A.
影响因子：
3.7
作者：
Cironi, Luisa;Riggi, Nicolo;Stamenkovic, Ivan
通讯作者：
Stamenkovic, Ivan
影响因子：
45.3
作者：
Cotterill, SJ;Ahrens, S;Craft, AW
通讯作者：
Craft, AW
影响因子：
64.8
作者：
DELATTRE, O;ZUCMAN, J;THOMAS, G
通讯作者：
THOMAS, G
影响因子：
3.2
作者：
Kolb, E. Anders;Gorlick, Richard;Smith, Malcolm A.
通讯作者：
Smith, Malcolm A.