Weil R J, Wu Y Y, Vortmeyer A O, Moon Y W, Delgado R M, Fuller B G, Lonser R R, Remaley A T, Zhuang Z
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Mod Pathol. 1999 Jan;12(1):41-6.
Future improvements in the diagnosis and treatment of human gliomas might rely on obtaining more specific information concerning the biologic characteristics of individual tumor cells. Telomerase, a ribonucleoprotein that synthesizes telomeres, has been reported to be expressed in a majority of human tumors, including several subtypes of brain tumor. We hypothesized that a quantitative assay for telomerase activity, combined with selective microdissection of tumor or normal brain cells, might reveal telomerase gain-of-function to be important in the pathogenesis of gliomas and that telomerase levels might have prognostic significance. We used tissue microdissection for selective analysis of tumor cells obtained from eight patients with glioma, one with a meningioma, and one with a primary B-cell lymphoma of the central nervous system. Normal brain tissue microdissected from another patient was used as a control. Telomerase activity was screened by an electrophoretic method and then assayed by a quantitative ELISA method. All of the eight gliomas had positive telomerase activity, as did the lymphoma. The meningioma and normal brain were negative. Quantitative analysis of telomerase activity did not correlate with tumor grade nor predict outcome. Selective tissue microdissection, combined with qualitative and quantitative telomerase assays, permits rapid and reliable detection of telomerase activity in diverse brain tumor tissues. These preliminary findings suggest that telomerase reactivation is a frequent event in glioma tumorigenesis that can be sensitively and specifically detected in gliomas of all histologic grades. Furthermore, specific detection of telomerase reactivation represents another mechanism by which tumor formation and progression might become the target of novel therapeutics.
人类胶质瘤诊断和治疗的未来进展可能依赖于获取有关单个肿瘤细胞生物学特性的更具体信息。端粒酶是一种合成端粒的核糖核蛋白，据报道在大多数人类肿瘤中表达，包括几种脑肿瘤亚型。我们假设，端粒酶活性的定量测定，结合肿瘤或正常脑细胞的选择性显微切割，可能揭示端粒酶功能获得在胶质瘤发病机制中很重要，并且端粒酶水平可能具有预后意义。我们使用组织显微切割对从8例胶质瘤患者、1例脑膜瘤患者和1例中枢神经系统原发性B细胞淋巴瘤患者获取的肿瘤细胞进行选择性分析。从另一名患者显微切割的正常脑组织用作对照。通过电泳方法筛选端粒酶活性，然后通过定量ELISA方法进行测定。8例胶质瘤均具有阳性端粒酶活性，淋巴瘤也是如此。脑膜瘤和正常脑为阴性。端粒酶活性的定量分析与肿瘤分级无关，也不能预测预后。选择性组织显微切割结合端粒酶定性和定量测定，能够快速、可靠地检测不同脑肿瘤组织中的端粒酶活性。这些初步发现表明，端粒酶重新激活是胶质瘤肿瘤发生中的常见事件，在所有组织学分级的胶质瘤中都能灵敏且特异地检测到。此外，端粒酶重新激活的特异性检测代表了肿瘤形成和进展可能成为新型治疗靶点的另一种机制。
