两种内源性血管生成抑制剂，内皮抑素和血管抑肽，在其抗肿瘤谱中表现出双相曲线。
Two Endogenous Antiangiogenic Inhibitors, Endostatin and Angiostatin, Demonstrate Biphasic Curves in their Antitumor Profiles.
机构信息
Center of Cancer Systems Biology, Department of Medicine, St. Elizabeth's Medical Center, School of Medicine, Tufts University, Boston, MA, USA.
出版信息
Dose Response. 2011;9(3):369-76. doi: 10.2203/dose-response.10-020.Javaherian. Epub 2010 Oct 21.
Abstract
Angiogenesis refers to growth of blood vessels from pre-existing ones. In 1971, Folkman proposed that by choking off the blood supply to tumors, they are starved, leading to their demise. A few years ago, the monoclonal antibody Avastin became the first antiangiogenic biological approved by FDA, for treatment of cancer patients. Two other antiangiogenic endogenous protein fragments were isolated in Folkman's laboratory more than a decade ago. Here, we present a short review of data demonstrating that angiostatin and endostatin display a biphasic antitumor dose-response. This behavior is common among a large number of antiangiogenic agents and the reduced effectiveness of antiangiogenic agents at high dose rates may be due to suppression of growth of new vessels carrying the agent into the critical region around the tumor.
摘要
血管生成是指从预先存在的血管中生长出新的血管。1971 年，Folkman 提出通过阻断肿瘤的血液供应，使肿瘤饥饿，从而导致其死亡。几年前，单克隆抗体 Avastin 成为 FDA 批准的第一种抗血管生成生物制剂，用于治疗癌症患者。十多年前，Folkman 的实验室分离出另外两种抗血管生成内源性蛋白片段。在这里，我们简要回顾了一些数据，这些数据表明血管抑素和内皮抑素显示出双相抗肿瘤剂量反应。这种行为在大量抗血管生成药物中很常见，高剂量率下抗血管生成药物效果降低的原因可能是抑制了携带药物进入肿瘤周围关键区域的新血管的生长。
相似文献
1
Two Endogenous Antiangiogenic Inhibitors, Endostatin and Angiostatin, Demonstrate Biphasic Curves in their Antitumor Profiles.两种内源性血管生成抑制剂，内皮抑素和血管抑肽，在其抗肿瘤谱中表现出双相曲线。
Dose Response. 2011;9(3):369-76. doi: 10.2203/dose-response.10-020.Javaherian. Epub 2010 Oct 21.
2
Antitumor effects of angiostatin K1-3 and endostatin genes coadministered by the hydrodynamics-based transfection method.基于流体动力学转染法共给药血管抑素K1-3和内皮抑素基因的抗肿瘤作用
Oncol Res. 2005;15(7-8):343-50. doi: 10.3727/096504005776449707.
3
Synergy between angiostatin and endostatin: inhibition of ovarian cancer growth.血管抑素与内皮抑素之间的协同作用：对卵巢癌生长的抑制作用。
Cancer Res. 2000 Apr 15;60(8):2190-6.
4
Combination angiostatin and endostatin gene transfer induces synergistic antiangiogenic activity in vitro and antitumor efficacy in leukemia and solid tumors in mice.血管抑素和内皮抑素基因联合转移在体外诱导协同抗血管生成活性，并在小鼠白血病和实体瘤中具有抗肿瘤功效。
Mol Ther. 2001 Feb;3(2):186-96. doi: 10.1006/mthe.2000.0243.
5
Role of angiogenesis in tumor growth and metastasis.血管生成在肿瘤生长和转移中的作用。
Semin Oncol. 2002 Dec;29(6 Suppl 16):15-8. doi: 10.1053/sonc.2002.37263.
6
A Hypothesis Concerning the Biphasic Dose-response of Tumors to Angiostatin and Endostatin.关于肿瘤对血管抑素和内皮抑素双相剂量反应的一种假说。
Dose Response. 2015 May 20;13(2). doi: 10.2203/dose-response.14-020.Parris. eCollection 2015 Apr-Jun.
7
Statin-AE: a novel angiostatin-endostatin fusion protein with enhanced antiangiogenic and antitumor activity.
Angiogenesis. 2001;4(4):263-8. doi: 10.1023/a:1016067717433.
8
Endostatin: the logic of antiangiogenic therapy.内皮抑素：抗血管生成治疗的原理
Drug Resist Updat. 2005 Feb-Apr;8(1-2):59-74. doi: 10.1016/j.drup.2005.03.001. Epub 2005 Apr 7.
9
Recombinant adeno-associated virus 2-mediated antiangiogenic prevention in a mouse model of intraperitoneal ovarian cancer.重组腺相关病毒2介导的抗血管生成预防在腹腔内卵巢癌小鼠模型中的应用
Clin Cancer Res. 2005 Feb 1;11(3):1342-7.
10
[Tumor angiogenesis inhibitors: media and scientific aspects].[肿瘤血管生成抑制剂：媒体与科学视角]
Presse Med. 1998;27(24):1221-4.
引用本文的文献
1
Nonallosteric activation of posttranslational modification enzymes by active site-directed inhibitors.活性位点导向抑制剂对翻译后修饰酶的非别构激活作用。
Comput Struct Biotechnol J. 2023 Nov 14;23:34-42. doi: 10.1016/j.csbj.2023.11.019. eCollection 2024 Dec.
2
The relationship between radiation dose and bevacizumab-related imaging abnormality in patients with brain tumors: A voxel-wise normal tissue complication probability (NTCP) analysis.脑肿瘤患者的辐射剂量与贝伐珠单抗相关的影像学异常之间的关系：体素-wise 正常组织并发症概率（NTCP）分析。
PLoS One. 2023 Feb 17;18(2):e0279812. doi: 10.1371/journal.pone.0279812. eCollection 2023.
3
The novel transcriptomic signature of angiogenesis predicts clinical outcome, tumor microenvironment and treatment response for prostate adenocarcinoma.前列腺腺癌血管生成的新型转录组学特征可预测临床结局、肿瘤微环境和治疗反应。
Mol Med. 2022 Jul 14;28(1):78. doi: 10.1186/s10020-022-00504-6.
4
The Role of Angiogenesis in Cancer Treatment.血管生成在癌症治疗中的作用。
Biomedicines. 2017 Jun 21;5(2):34. doi: 10.3390/biomedicines5020034.
5
Analogs of the hepatocyte growth factor and macrophage-stimulating protein hinge regions act as Met and Ron dual inhibitors in pancreatic cancer cells.肝细胞生长因子和巨噬细胞刺激蛋白铰链区类似物在胰腺癌细胞中充当Met和Ron双抑制剂。
Anticancer Drugs. 2016 Sep;27(8):766-79. doi: 10.1097/CAD.0000000000000390.
6
Endostatin is protective against monocrotaline-induced right heart disease through the inhibition of T-type Ca(2+) channel.内皮抑素通过抑制T型钙通道对野百合碱诱导的右心疾病具有保护作用。
Pflugers Arch. 2016 Jul;468(7):1259-1270. doi: 10.1007/s00424-016-1810-0. Epub 2016 Mar 29.
7
Matricryptins Network with Matricellular Receptors at the Surface of Endothelial and Tumor Cells.基质隐窝蛋白在内皮细胞和肿瘤细胞表面与基质细胞受体形成网络。
Front Pharmacol. 2016 Feb 4;7:11. doi: 10.3389/fphar.2016.00011. eCollection 2016.
8
A Hypothesis Concerning the Biphasic Dose-response of Tumors to Angiostatin and Endostatin.关于肿瘤对血管抑素和内皮抑素双相剂量反应的一种假说。
Dose Response. 2015 May 20;13(2). doi: 10.2203/dose-response.14-020.Parris. eCollection 2015 Apr-Jun.
9
Inhibition of Corneal Neovascularization by Subconjunctival Injection of Fc-Endostatin, a Novel Inhibitor of Angiogenesis.结膜下注射新型血管生成抑制剂Fc-内皮抑素对角膜新生血管形成的抑制作用
J Ophthalmol. 2015;2015:137136. doi: 10.1155/2015/137136. Epub 2015 Sep 28.
10
Endostatin's emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications.内皮抑素在血管生成、淋巴管生成、疾病及临床应用中的新作用。
Biochim Biophys Acta. 2015 Dec;1850(12):2422-38. doi: 10.1016/j.bbagen.2015.09.007. Epub 2015 Sep 12.
本文引用的文献
1
Angiostatin regulates the expression of antiangiogenic and proapoptotic pathways via targeted inhibition of mitochondrial proteins.血管抑素通过靶向抑制线粒体蛋白来调节抗血管生成和促凋亡途径的表达。
Blood. 2009 Aug 27;114(9):1987-98. doi: 10.1182/blood-2008-12-197236. Epub 2009 May 22.
2
Linking antibody Fc domain to endostatin significantly improves endostatin half-life and efficacy.将抗体Fc结构域与内皮抑素连接可显著提高内皮抑素的半衰期和疗效。
Clin Cancer Res. 2008 Mar 1;14(5):1487-93. doi: 10.1158/1078-0432.CCR-07-1530.
3
Endostatin therapy reveals a U-shaped curve for antitumor activity.内皮抑素疗法显示出抗肿瘤活性的U形曲线。
Cancer Gene Ther. 2006 Jun;13(6):619-27. doi: 10.1038/sj.cgt.7700938.
4
Antiangiogenesis in cancer therapy--endostatin and its mechanisms of action.癌症治疗中的抗血管生成——内皮抑素及其作用机制。
Exp Cell Res. 2006 Mar 10;312(5):594-607. doi: 10.1016/j.yexcr.2005.11.015. Epub 2005 Dec 22.
5
Therapeutic efficacy of endostatin exhibits a biphasic dose-response curve.内皮抑素的治疗效果呈现出双相剂量反应曲线。
Cancer Res. 2005 Dec 1;65(23):11044-50. doi: 10.1158/0008-5472.CAN-05-2617.
6
Angiostatin's molecular mechanism: aspects of specificity and regulation elucidated.血管抑素的分子机制：特异性和调控方面得以阐明。
J Cell Biochem. 2005 Oct 1;96(2):242-61. doi: 10.1002/jcb.20480.
7
Endostatin: the logic of antiangiogenic therapy.内皮抑素：抗血管生成治疗的原理
Drug Resist Updat. 2005 Feb-Apr;8(1-2):59-74. doi: 10.1016/j.drup.2005.03.001. Epub 2005 Apr 7.
8
A 27-amino-acid synthetic peptide corresponding to the NH2-terminal zinc-binding domain of endostatin is responsible for its antitumor activity.一种与内皮抑素NH2末端锌结合结构域相对应的27个氨基酸的合成肽负责其抗肿瘤活性。
Cancer Res. 2005 May 1;65(9):3656-63. doi: 10.1158/0008-5472.CAN-04-1833.
9
Nonmonotonic dose-response relationships: mechanistic basis, kinetic modeling, and implications for risk assessment.非单调剂量反应关系：机制基础、动力学建模及其对风险评估的意义。
Toxicol Sci. 2004 Jan;77(1):151-7. doi: 10.1093/toxsci/kfh007. Epub 2003 Nov 4.
10
Evidence of a bi-phasic effect of thrombospondin-1 on angiogenesis.血小板反应蛋白-1对血管生成的双相效应的证据。
Histochem J. 2002 Aug-Sep;34(8-9):411-21. doi: 10.1023/a:1023687505139.
Zotero 插件