PROGNOSTIC-SIGNIFICANCE OF PROTEOLYTIC-ENZYMES IN HUMAN BRAIN-TUMORS
PROGNOSTIC-SIGNIFICANCE OF PROTEOLYTIC-ENZYMES IN HUMAN BRAIN-TUMORS
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DOI：
10.1007/bf01052886
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发表时间：
1994-01-01
影响因子：
3.9
通讯作者：
RAO, JS
中科院分区：
文献类型：
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作者：
BINDAL, AK;HAMMOUD, M;RAO, JS
在许多实验模型中，蛋白酶及其抑制剂已被证明在肿瘤侵袭和转移中发挥作用。近年来，尿激酶型纤溶酶原激活剂（uPA）和纤溶酶原激活剂抑制剂-1 （PAI-1）在肿瘤样本中含量的相对增加与较差的病理分级、较短的无病间期和较短的生存期相关。迄今为止，所有调查蛋白酶及其抑制剂预后意义的研究都局限于颅外癌。在这篇文章中，我们回顾了文献，并提出了我们的数据在人类脑肿瘤的预后意义蛋白酶。恶性胶质瘤和转移瘤中可见高水平的uPA (n = 82)，而在二级胶质瘤中发现正常水平的uPA。磁共振成像（MRI）分析显示，高水平的uPA与坏死和水肿有显著相关性（n = 50; P < 0.05）。同样，uPA水平高的患者比uPA水平低的患者生存时间短。组织型纤溶酶原激活剂（tPA）在多形性胶质母细胞瘤（GBM）、结肠、肺和乳腺转移中几乎不存在，但在间变性星形细胞瘤（AA）、低级别胶质瘤（LGG）和脑膜瘤中发现了正常数量的tPA。黑色素瘤的tPA活性明显高于正常大脑。tPA与MRI显示的坏死、强化和水肿呈负相关。同样，tPA活性检测不到的患者的生存期比tPA活性检测到的患者短。我们得出结论，高水平的uPA和缺乏tPA活性与组织学上恶性脑肿瘤、侵袭性特征和较短的生存期相关。
Proteases and their inhibitors have been shown to play roles in tumor invasion and metastasis in a number of experimental models. Recently, relative increases in the amounts of urokinase type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in tumor samples have been correlated with poorer pathological grade, shorter disease-free interval, and shorter survival. To date, all studies investigating the prognostic significance of proteases and their inhibitors have been limited to extracranial cancer. In this article, we review the literature and present our data on the prognostic significance of proteases in human brain tumors. High levels of uPA were seen in malignant glioma and metastatic tumors (n = 82), whereas normal levels of uPA were found in tow-grade gliomas. Analysis with magnetic resonance imaging (MRI) demonstrated a significant correlation between high levels of uPA and necrosis and edema (n = 50; P < 0.05). Similarly, patients with high levels of uPA had shorter survival than did patients with low levels of uPA.Tissue-type plasminogen activator (tPA), which was virtually absent in glioblastoma multiforme (GBM), colon, lung, and breast metastasis, was found in normal quantities in anaplastic astrocytoma (AA), low-grade glioma (LGG), and meningioma. Melanoma had significantly more tPA activity than normal brain did. A reverse correlation was found between tPA and MRI findings of necrosis, enhancement, and edema. Similarly, patients with no detectable tPA activity had shorter survival than did patients with detectable tPA activity. We conclude that high levels of uPA and absent tPA activity correlate with histologically malignant brain tumors, aggressive characteristics, and shorter survival.