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AGM-1470(TNP-470)用于鼻咽癌实验性抗血管生成治疗的初步研究。

Primary study in experimental antiangiogenic therapy of nasopharyngeal carcinoma with AGM-1470 (TNP-470).

作者信息

Qian C N, Min H Q, Lin H L, Hong M H, Ye Y L

机构信息

Department of Nasopharyngeal Carcinoma, Tumor Hospital, Sun Yat-sen University of Medical Sciences, (SUMS), Guangzhou, P.R. of China.

出版信息

J Laryngol Otol. 1998 Sep;112(9):849-53. doi: 10.1017/s0022215100141878.

DOI:10.1017/s0022215100141878
PMID:9876375
Abstract

OBJECTIVE

To evaluate the efficacy of the angiogenesis inhibitor AGM-1470 for the experimental treatment of nasopharyngeal carcinoma (NPC).

METHODS

A NPC human tumour model was built by tumour-bearing nude mice using the NPC cell line CNE-2. Twenty-one BALB/c nude mice bearing CNE-2 xenografts were randomized into a treatment group and a control group. In the treatment group, AGM-1470 was injected 30 mg/kg subcutaneously every other day; while the vehicle (three per cent ethanol solution in 0.9 per cent saline) was given to the mice in control group. Tumour volumes and animal weights were measured every third day. Autopsy was performed after 18 days of treatment. The tumour tissue as well as the murine tissues of heart, kidney, and liver in each mouse were removed for formalin fixation and routine HE staining. Pathological evaluation was performed in these tissues.

RESULTS

There was a significant difference in tumour volume between the two groups at day 9 of treatment and this increased thereafter. At day 15 of treatment, the tumour volume was 4251 +/- 559 mm3 (n = 10) in the control group versus 3122 +/- 967 mm3 (n = 11) in the AGM-1470 treated group (p = 0.004); and T:C ratio (mean tumour volume of treated/mean tumour volume of control) was 0.73, resulting in a 27 per cent decrease in tumour growth. Central necrosis and consequential shrinkage of tumours occurred in both groups at the end of experiment. Physical toxicity and histological toxicity of heart, liver, and kidney did not result from AGM-1470 therapy.

CONCLUSIONS

AGM-1470 suppresses the growth of the human NPC cell line CNE-2. Treatment by AGM-1470 has no physical nor histological toxicity. Angiogenesis inhibitors may be effective in the treatment of the local lesion of NPC.

摘要

目的

评估血管生成抑制剂AGM - 1470对鼻咽癌(NPC)进行实验性治疗的疗效。

方法

采用鼻咽癌细胞系CNE - 2,通过荷瘤裸鼠建立NPC人肿瘤模型。将21只携带CNE - 2异种移植物的BALB/c裸鼠随机分为治疗组和对照组。治疗组每隔一天皮下注射30 mg/kg的AGM - 1470;对照组小鼠则给予赋形剂(0.9%盐水中的3%乙醇溶液)。每三天测量肿瘤体积和动物体重。治疗18天后进行尸检。取出每只小鼠的肿瘤组织以及心脏、肾脏和肝脏的鼠组织,用福尔马林固定并进行常规苏木精-伊红染色。对这些组织进行病理评估。

结果

治疗第9天时,两组肿瘤体积存在显著差异,此后差异增大。治疗第15天时,对照组肿瘤体积为4251±559 mm³(n = 10),而AGM - 1470治疗组为3122±967 mm³(n = 11)(p = 0.004);治疗组与对照组的肿瘤体积比(T:C比,即治疗组平均肿瘤体积/对照组平均肿瘤体积)为0.73,肿瘤生长减少了27%。实验结束时,两组均出现肿瘤中央坏死及随之而来的肿瘤缩小。AGM - 1470治疗未导致心脏、肝脏和肾脏的物理毒性及组织学毒性。

结论

AGM - 1470可抑制人鼻咽癌细胞系CNE - 2的生长。AGM - 1470治疗无物理毒性和组织学毒性。血管生成抑制剂可能对鼻咽癌局部病变的治疗有效。

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