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从组织学正常的脑组织中分离并鉴定人恶性胶质瘤细胞。

Isolation and characterization of human malignant glioma cells from histologically normal brain.

作者信息

Silbergeld D L, Chicoine M R

机构信息

Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.

出版信息

J Neurosurg. 1997 Mar;86(3):525-31. doi: 10.3171/jns.1997.86.3.0525.

DOI:10.3171/jns.1997.86.3.0525
PMID:9046311
Abstract

Brain invasion prevents complete surgical extirpation of malignant gliomas; however, invasive cells from distant, histologically normal brain previously have not been isolated, cultured, and characterized. To evaluate invasive human malignant glioma cells, the authors established cultures from gross tumor and histologically normal brain. Three men and one woman, with a mean age of 67 years, underwent two frontal and two temporal lobectomies for tumors, which yielded specimens of both gross tumor and histologically normal brain. Each specimen was acquired a minimum of 4 cm from the gross tumor. The specimens were split: a portion was sent for neuropathological evaluation (three glioblastomas multiforme and one oligodendroglioma) and a portion was used to establish cell lines. Morphologically, the specimens of gross tumor and histologically normal brain were identical in three of the four cell culture pairs. Histochemical staining characteristics were consistent both within each pair and when compared with the specimens sent for neuropathological evaluation. Cultures demonstrated anchorage-independent growth in soft agarose and neoplastic karyotypes. Growth rates in culture were greater for histologically normal brain than for gross tumor in three of the four culture pairs. Although the observed increases in growth rates of histologically normal brain cultures do not correlate with in vivo behavior, these findings corroborate the previously reported stem cell potential of invasive glioma cells. Using the radial dish assay, no significant differences in motility between cultures of gross tumor and histologically normal brain were found. In summary, tumor cells were cultured from histologically normal brain acquired from a distance greater than 4 cm from the gross tumor, indicating the relative insensitivity of standard histopathological identification of invasive glioma cells (and hence the inadequacy of frozen-section evaluation of resection margins). Cell lines derived from gross tumor and histologically normal brain were usually histologically identical and demonstrated equivalent motility, but had different growth rates.

摘要

脑侵袭会妨碍恶性胶质瘤的完全手术切除;然而,此前尚未分离、培养和鉴定来自远处组织学正常脑区的侵袭性细胞。为了评估侵袭性人类恶性胶质瘤细胞,作者从大体肿瘤和组织学正常的脑组织中建立了培养物。3名男性和1名女性,平均年龄67岁,因肿瘤接受了两次额叶和两次颞叶切除术,获得了大体肿瘤和组织学正常脑的标本。每个标本均取自距大体肿瘤至少4厘米处。标本被分开:一部分送去进行神经病理学评估(3例多形性胶质母细胞瘤和1例少突胶质细胞瘤),一部分用于建立细胞系。形态学上,在四组细胞培养物中的三组中,大体肿瘤标本和组织学正常脑标本是相同的。组织化学染色特征在每组内以及与送去进行神经病理学评估的标本相比时都是一致的。培养物在软琼脂糖中显示出不依赖贴壁生长和肿瘤核型。在四组培养物中的三组中,组织学正常脑培养物在培养中的生长速率大于大体肿瘤。尽管观察到的组织学正常脑培养物生长速率的增加与体内行为无关,但这些发现证实了先前报道的侵袭性胶质瘤细胞的干细胞潜能。使用放射状培养皿试验,未发现大体肿瘤培养物和组织学正常脑培养物之间的运动性有显著差异。总之,从距大体肿瘤大于4厘米处获取的组织学正常脑培养出了肿瘤细胞,这表明侵袭性胶质瘤细胞的标准组织病理学鉴定相对不敏感(因此,切除边缘的冰冻切片评估存在不足)。源自大体肿瘤和组织学正常脑的细胞系通常在组织学上相同,显示出相同的运动性,但生长速率不同。

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