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本文引用的文献

1
Igf1r as a therapeutic target in a mouse model of basal-like breast cancer.胰岛素样生长因子1受体（Igf1r）作为基底样乳腺癌小鼠模型中的治疗靶点。
Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2359-64. doi: 10.1073/pnas.0810221106. Epub 2009 Jan 27.
2
PTEN has tumor-promoting properties in the setting of gain-of-function p53 mutations.在功能获得性p53突变的情况下，PTEN具有促肿瘤特性。
Cancer Res. 2008 Mar 15;68(6):1723-31. doi: 10.1158/0008-5472.CAN-07-1963.
3
Modifying IGF1 activity: an approach to treat endocrine disorders, atherosclerosis and cancer.调节胰岛素样生长因子1（IGF1）的活性：一种治疗内分泌疾病、动脉粥样硬化和癌症的方法。
Nat Rev Drug Discov. 2007 Oct;6(10):821-33. doi: 10.1038/nrd2359.
4
Picropodophyllin induces downregulation of the insulin-like growth factor 1 receptor: potential mechanistic involvement of Mdm2 and beta-arrestin1.小檗碱木脂素诱导胰岛素样生长因子1受体下调：Mdm2和β-抑制蛋白1可能的机制参与
Oncogene. 2008 Mar 6;27(11):1629-38. doi: 10.1038/sj.onc.1210797. Epub 2007 Sep 10.
5
Influence of breast cancer resistance protein (Abcg2) and p-glycoprotein (Abcb1a) on the transport of imatinib mesylate (Gleevec) across the mouse blood-brain barrier.乳腺癌耐药蛋白（Abcg2）和P-糖蛋白（Abcb1a）对甲磺酸伊马替尼（格列卫）跨小鼠血脑屏障转运的影响。
J Neurochem. 2007 Sep;102(6):1749-1757. doi: 10.1111/j.1471-4159.2007.04808.x. Epub 2007 Aug 13.
6
Targeting the IGF-1R using picropodophyllin in the therapeutical 5T2MM mouse model of multiple myeloma: beneficial effects on tumor growth, angiogenesis, bone disease and survival.在多发性骨髓瘤的治疗性5T2MM小鼠模型中使用鬼臼苦素靶向胰岛素样生长因子-1受体（IGF-1R）：对肿瘤生长、血管生成、骨病和生存的有益作用。
Int J Cancer. 2007 Oct 15;121(8):1857-61. doi: 10.1002/ijc.22845.
7
Optimized protein extraction from cryopreserved brain tissue samples.从冷冻保存的脑组织样本中优化蛋白质提取。
Acta Oncol. 2007;46(1):10-20. doi: 10.1080/02841860600847061.
8
Activation of a novel calcineurin-mediated insulin-like growth factor-1 receptor pathway, altered metabolism, and tumor cell invasion in cells subjected to mitochondrial respiratory stress.在遭受线粒体呼吸应激的细胞中，一种新的钙调神经磷酸酶介导的胰岛素样生长因子-1受体途径被激活，代谢改变，肿瘤细胞侵袭发生变化。
J Biol Chem. 2007 May 11;282(19):14536-46. doi: 10.1074/jbc.M611693200. Epub 2007 Mar 13.
9
Insulin-like growth factor type I biology and targeting in malignant gliomas.胰岛素样生长因子I型在恶性胶质瘤中的生物学特性及靶向作用
Neuroscience. 2007 Mar 30;145(3):795-811. doi: 10.1016/j.neuroscience.2007.01.021. Epub 2007 Feb 21.
10
Heterodimerization of insulin-like growth factor receptor/epidermal growth factor receptor and induction of survivin expression counteract the antitumor action of erlotinib.胰岛素样生长因子受体/表皮生长因子受体的异源二聚化及生存素表达的诱导抵消了厄洛替尼的抗肿瘤作用。
Cancer Res. 2006 Oct 15;66(20):10100-11. doi: 10.1158/0008-5472.CAN-06-1684.

以苦鬼臼毒素为靶点的胰岛素样生长因子-1 受体治疗胶质母细胞瘤。

Targeting the insulin-like growth factor-1 receptor by picropodophyllin as a treatment option for glioblastoma.

机构信息

Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, 17176 Stockholm, Sweden.

出版信息

Neuro Oncol. 2010 Jan;12(1):19-27. doi: 10.1093/neuonc/nop008. Epub 2009 Oct 20.

DOI:10.1093/neuonc/nop008
PMID:20150364
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2940558/
Abstract

Glioblastoma (GB) is the most common malignant brain tumor in adults. It has limited treatment opportunities and is almost exclusively fatal. Owing to the central role the insulin-like growth factor-1 receptor (IGF-1R) plays in malignant cells, it has been suggested as a target for anticancer therapy including GB. The cyclolignan picropodophyllin (PPP) inhibits IGF-1R without affecting the highly homologous insulin receptor. Here, we show that PPP inhibits growth of human GB cell lines along with reduced phosphorylation of IGF-1R and AKT. In vivo, PPP-treatment causes dramatic tumor regression not only in subcutaneous xenografts but also in intracerebral xenografts, indicating passage of PPP across the blood-brain barrier.

摘要

胶质母细胞瘤（GB）是成人中最常见的恶性脑肿瘤。它的治疗机会有限，几乎是致命的。由于胰岛素样生长因子-1 受体（IGF-1R）在恶性细胞中起着核心作用，它已被提议作为抗癌治疗的靶点，包括 GB。环木脂素 picropodophyllin（PPP）抑制 IGF-1R 而不影响高度同源的胰岛素受体。在这里，我们表明 PPP 抑制人类 GB 细胞系的生长，同时减少 IGF-1R 和 AKT 的磷酸化。在体内，PPP 治疗不仅在皮下异种移植中，而且在颅内异种移植中引起明显的肿瘤消退，表明 PPP 穿过血脑屏障。