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血管生成抑制剂TNP - 470可降低人神经母细胞瘤在裸鼠体内的生长速率。

The angiogenesis inhibitor TNP-470 reduces the growth rate of human neuroblastoma in nude rats.

作者信息

Wassberg E, Påhlman S, Westlin J E, Christofferson R

机构信息

Department of Human Anatomy, University of Uppsala, Sweden.

出版信息

Pediatr Res. 1997 Mar;41(3):327-33. doi: 10.1203/00006450-199703000-00004.

DOI:10.1203/00006450-199703000-00004
PMID:9078530
Abstract

A new animal experimental model of human neuroblastoma is described. The model involves xenotransplantation of a poorly differentiated human neuroblastoma cell line (SH-SY5Y) to the subcutaneous tissue in the hind leg of nude rats (WAG mu/rnu). Injection of 20 million cells suspended in 0.2 mL of medium in each hind leg yielded an 89% tumor take (41/46) in 23 nude rats. Tumor take was evident after 2 wk. The tumors grew exponentially and reached a volume of 5.2 +/- 1.6 mL 4 wk after transplantation. The tumor cells retained their morphologic phenotype at the ultrastructural level after transplantation and were immunohistochemically positive for neuron-specific enolase and for chromogranins A and B. Subcutaneous injections of the angiogenesis inhibitor TNP-470 (10 mg/kg of body weight) every other day gave a treated/control quotient for mean tumor volume of 0.34 after 12 d of treatment. This implies that angiogenesis inhibition may be of value as a complement to chemotherapy in the treatment of human neuroblastoma. The presented animal experimental model is designed for investigations of the effects of chemotherapy, angiogenesis inhibitors, radiotherapy, and/or surgery on the growth rate of human neuroblastoma.

摘要

本文描述了一种新的人类神经母细胞瘤动物实验模型。该模型涉及将一种低分化人类神经母细胞瘤细胞系(SH-SY5Y)异种移植到裸鼠(WAG mu/rnu)后腿的皮下组织。在每只后腿注射悬浮于0.2 mL培养基中的2000万个细胞,在23只裸鼠中产生了89%的肿瘤形成率(41/46)。2周后肿瘤形成明显。肿瘤呈指数生长,移植后4周体积达到5.2±1.6 mL。移植后肿瘤细胞在超微结构水平保留其形态学表型,并且神经元特异性烯醇化酶以及嗜铬粒蛋白A和B免疫组化呈阳性。每隔一天皮下注射血管生成抑制剂TNP-470(10 mg/kg体重),治疗12天后治疗组/对照组平均肿瘤体积的比值为0.34。这意味着血管生成抑制作为人类神经母细胞瘤化疗的补充可能具有价值。所呈现的动物实验模型旨在研究化疗、血管生成抑制剂、放疗和/或手术对人类神经母细胞瘤生长速率的影响。

相似文献

1
The angiogenesis inhibitor TNP-470 reduces the growth rate of human neuroblastoma in nude rats.血管生成抑制剂TNP - 470可降低人神经母细胞瘤在裸鼠体内的生长速率。
Pediatr Res. 1997 Mar;41(3):327-33. doi: 10.1203/00006450-199703000-00004.
2
Inhibition of angiogenesis induces chromaffin differentiation and apoptosis in neuroblastoma.血管生成的抑制诱导神经母细胞瘤中的嗜铬细胞分化和凋亡。
Am J Pathol. 1999 Feb;154(2):395-403. doi: 10.1016/S0002-9440(10)65286-8.
3
Effectiveness of the angiogenesis inhibitor TNP-470 in reducing the growth of human neuroblastoma in nude mice inversely correlates with tumor burden.血管生成抑制剂TNP - 470在裸鼠体内抑制人神经母细胞瘤生长的有效性与肿瘤负荷呈负相关。
Clin Cancer Res. 1999 Dec;5(12):4273-8.
4
Antiangiogenic therapy inhibits human neuroblastoma growth.抗血管生成疗法可抑制人类神经母细胞瘤的生长。
Med Pediatr Oncol. 2001 Jan;36(1):190-3. doi: 10.1002/1096-911X(20010101)36:1<190::AID-MPO1045>3.0.CO;2-I.
5
Angiostatic treatment of neuroblastoma.神经母细胞瘤的血管生成抑制治疗
Eur J Cancer. 1997 Oct;33(12):2020-3. doi: 10.1016/s0959-8049(97)00337-7.
6
Inhibitory effect of TNP-470 on hepatic metastasis of mouse neuroblastoma.TNP - 470对小鼠神经母细胞瘤肝转移的抑制作用
J Surg Res. 2000 Sep;93(1):82-7. doi: 10.1006/jsre.2000.5956.
7
Angiogenesis can be reduced without significant reduction of tumor growth.血管生成可以被减少,而肿瘤生长不会显著降低。
Anticancer Res. 2007 Nov-Dec;27(6B):3883-9.
8
TNP-470 antiangiogenic therapy for advanced murine neuroblastoma.TNP - 470对晚期小鼠神经母细胞瘤的抗血管生成治疗
J Pediatr Surg. 1997 Feb;32(2):287-93. doi: 10.1016/s0022-3468(97)90196-2.
9
The angiogenesis inhibitor tnp-470 effectively inhibits human neuroblastoma xenograft growth, especially in the setting of subclinical disease.血管生成抑制剂tnp - 470能有效抑制人神经母细胞瘤异种移植瘤的生长,尤其是在亚临床疾病的情况下。
Clin Cancer Res. 2001 Apr;7(4):977-84.
10
The bisphosphonate, zoledronic acid reduces experimental neuroblastoma growth by interfering with tumor angiogenesis.双膦酸盐唑来膦酸通过干扰肿瘤血管生成来抑制实验性神经母细胞瘤的生长。
Anticancer Res. 2008 May-Jun;28(3A):1551-7.

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Developing preclinical models of neuroblastoma: driving therapeutic testing.开发神经母细胞瘤的临床前模型:推动治疗测试。
BMC Biomed Eng. 2019 Dec 20;1:33. doi: 10.1186/s42490-019-0034-8. eCollection 2019.
2
The novel kinase inhibitor ponatinib is an effective anti-angiogenic agent against neuroblastoma.新型激酶抑制剂波纳替尼是一种有效的抗神经母细胞瘤血管生成药物。
Invest New Drugs. 2016 Dec;34(6):685-692. doi: 10.1007/s10637-016-0387-y. Epub 2016 Sep 1.
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Neuroblastoma.神经母细胞瘤
Semin Pediatr Surg. 2012 Feb;21(1):2-14. doi: 10.1053/j.sempedsurg.2011.10.009.
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PPARgamma in Neuroblastoma.过氧化物酶体增殖物激活受体 γ 在神经母细胞瘤中的作用。
PPAR Res. 2008;2008:917815. doi: 10.1155/2008/917815.
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Malignant progression and blockade of angiogenesis in a murine transgenic model of neuroblastoma.神经母细胞瘤小鼠转基因模型中的恶性进展与血管生成阻断
Cancer Res. 2007 Oct 1;67(19):9435-42. doi: 10.1158/0008-5472.CAN-07-1316.
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Noninvasive estimation of tumour viability in a xenograft model of human neuroblastoma with proton magnetic resonance spectroscopy (1H MRS).利用质子磁共振波谱(1H MRS)对人神经母细胞瘤异种移植模型中的肿瘤活力进行无创估计。
Br J Cancer. 2003 Feb 10;88(3):478-85. doi: 10.1038/sj.bjc.6600704.
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Antitumor effect of TNP-470 is not associated to decrease of angiogenesis in an experimental malignant neuroectodermic tumor.TNP - 470的抗肿瘤作用与实验性恶性神经外胚层肿瘤中血管生成的减少无关。
J Neurooncol. 2002 Jun;58(2):131-6. doi: 10.1023/a:1016039411914.
8
Bioavailability and dose-dependent anti-tumour effects of 9-cis retinoic acid on human neuroblastoma xenografts in rat.9-顺式视黄酸对大鼠人神经母细胞瘤异种移植瘤的生物利用度及剂量依赖性抗肿瘤作用
Br J Cancer. 2001 Dec 14;85(12):2004-9. doi: 10.1054/bjoc.2001.2186.
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Anti-angiogenic treatment strategies for malignant brain tumors.恶性脑肿瘤的抗血管生成治疗策略
J Neurooncol. 2000 Oct-Nov;50(1-2):149-63. doi: 10.1023/a:1006487412567.
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[Anti-angiogenesis: a new approach to tumor therapy?].抗血管生成:肿瘤治疗的新方法?
Med Klin (Munich). 1999 Oct 15;94(10):570-9. doi: 10.1007/BF03044955.