Evaluation of the efficiency of chemotherapy in in vivo orthotopic models of human glioma cells with and without 1p19q deletions and in C6 rat orthotopic allografts serving for the evaluation of surgery combined with chemotherapy
Evaluation of the efficiency of chemotherapy in in vivo orthotopic models of human glioma cells with and without 1p19q deletions and in C6 rat orthotopic allografts serving for the evaluation of surgery combined with chemotherapy
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DOI：
10.1002/cncr.10710
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发表时间：
2002-08-01
期刊：
影响因子：
6.2
通讯作者：
Salmon, I
中科院分区：
文献类型：
--
作者：
Branle, F;Lefranc, F;Salmon, I
背景资料。中枢神经系统恶性胶质瘤由于弥漫性侵犯脑实质，预后较差。目前，几乎没有模拟临床现实的实验模型可用于测试潜在的新疗法。作者建立了人和大鼠来源的间变性星形细胞瘤和人源性间变性少突胶质细胞瘤的体内实验模型。采用标准的医院化疗方法来验证这些模型的有效性。方法：从美国典型培养库中获得3个胶质瘤细胞系(即人Hs683和U373细胞和大鼠C6细胞)，将其移植到裸鼠脑(Hs683和U373细胞)和大鼠脑(C6细胞)中。用免疫组织化学定量方法(计算机辅助显微镜)检测Hs683和U373模型中巢蛋白、波形蛋白、谷胱甘肽S转移酶α、谷胱甘肽转移酶u、谷胱甘肽转移酶p1和p53的表达，观察其星形胶质细胞性质，而不是少突胶质细胞性质。比较基因组杂交(CGH)检测1p19q缺失。在异种移植的U373和Hs683模型上，检测了卡莫司汀(BCNU)、福替斯汀或替莫唑胺的长期给药情况。结果定量表型分析表明，Hs683细胞系具有少突胶质细胞性质，U373细胞系具有星形胶质细胞性质。Hs683细胞有1p19q缺失，而U373细胞无此现象。BCNU、福替斯汀和替莫唑胺显著延长了Hs683少突胶质瘤小鼠的存活时间，而替莫唑胺仅对U373胶质瘤小鼠有微弱的诱导作用，但仍有统计学意义。在C6大鼠脑胶质瘤模型中，手术加BCNU化疗比任何一种单独治疗都更有效。结论：本工作建立的中枢神经系统脑胶质瘤体内模型最接近临床实际。它们既可用于确定针对人类胶质瘤的新疗法，也可用于优化现有疗法。(C)2002年美国癌症协会。
BACKGROUND. Malignant gliomas of the central nervous system remain associated with dismal prognoses because of their diffuse invasion of the brain parenchyma. Very few experimental models that mimic clinical reality are available today to test potentially new therapies. The authors set up experimental in vivo glioma models of anaplastic astrocytomas of human and rat origins and anaplastic oligodendroglioma of human origin. Standard hospital chemotherapies were employed to test the validity of these models.METHODS. Three glioma cells lines obtained from the American Type Culture Collection (i.e., human Hs683 and U373 cells and rat C6 cells) were implanted into nude mouse brains (Hs683 and U373 cells) and rat brains (C6 cells). The astrocytic nature, as opposed to the oligodendrocytic nature, of the Hs683 and U373 models was investigated by using quantitative (computer-assisted microscopy) immunohistochemical characterizations of nestin, vimentin, glutathione-S-transferase alpha (GSTalpha), GSTmu, GSTpi, and p53 expression. Comparative genomic hybridization (CGH) was employed to investigate 1p19q losses. Chronic administrations of carmustine (BCNU), fotemustin, or temozolomide were assayed in the xenografted U373 and Hs683 models. Both BCNU-related chemotherapy and surgery were assayed in the C6 model.RESULTS. The quantitative phenotypic analyses pointed to the oligodendroglial nature of the Hs683 cell line and the astrocytic nature of the U373 cell line. The Hs683 cells exhibited 1p19q losses, whereas the U373 cells did not. BCNU, fotemustin, and temozolomide dramatically increased the time of survival of the Hs683 oligodendroglioma-bearing mice, whereas temozolomide only induced a weak but nevertheless statistically significant increase in the U373 glioma-bearing mice. In the C6 rat glioma model, surgery and BCNU chemotherapy were more efficient than either treatment alone.CONCLUSIONS. The in vivo models of gliomas of the central nervous system developed in the current work best mimicked clinical reality. They can be used either to identify new therapies against human gliomas or to optimize existing therapies. (C) 2002 American Cancer Society.