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喉鳞状细胞癌中前半胱天冬酶-3和活化半胱天冬酶-3的免疫组织化学分析

Immunohistochemical analysis of pro- and active-caspase 3 in laryngeal squamous cell carcinoma.

作者信息

Cör Andrej, Pizem Joze, Gale Nina

机构信息

Institute for Histology and Embryology, Medical Faculty of Ljubljana, Korytkova 2, 1000, Ljubljana, Slovenia,

出版信息

Virchows Arch. 2004 May;444(5):439-46. doi: 10.1007/s00428-004-0997-1. Epub 2004 Mar 25.

Abstract

Active caspase 3 is considered to be the main executioner caspase in apoptotic process. The mechanisms of apoptosis in laryngeal squamous cell carcinoma (LSCC) have been investigated by examining the expression profiles of pro-caspase 3 and active-caspase 3. The correlation between the two forms of caspase 3 and the p53 status was also determined. LSCCs ( n=65) were studied using immunohistochemistry with antibodies to pro-caspase 3, active-caspase 3 and p53. The expression of pro-caspase 3 was absent or weak in 16 (24.6%), moderate in 21 (32.3%) and strong in 28 (43.1%) cases. Survival curves for different levels of pro-caspase 3 differed, but the differences were not statistically significant. An apoptotic index (AI) was determined by quantifying the active-caspase 3-positive cells. The AI ranged from 0.2% to 9.4% and did not differ among the different levels of pro-caspase 3 expression. Even in cases in which the expression of pro-caspase 3 was considered negative, caspase 3-positive apoptotic cells were found. The AIs were significantly higher in supraglottic tumours compared with glottic counterparts ( P=0.008) and were higher in poorly differentiated tumours compared with well-differentiated and moderately differentiated LSCC ( P=0.06). No correlation between AI and p53 expression was found, although pro-caspase 3 expression trended to be higher in the p53-positive group of LSCC. Our results suggest that the expression of pro-caspase 3, a key executioner caspase in apoptosis, is downregulated in a proportion of LSCC, but this is not associated with decreased apoptotic activity, measured by active-caspase 3 labelling.

摘要

活化的半胱天冬酶-3被认为是凋亡过程中的主要执行性半胱天冬酶。通过检测前体半胱天冬酶-3和活化的半胱天冬酶-3的表达谱,对喉鳞状细胞癌(LSCC)的凋亡机制进行了研究。还确定了两种形式的半胱天冬酶-3与p53状态之间的相关性。使用针对前体半胱天冬酶-3、活化的半胱天冬酶-3和p53的抗体,通过免疫组织化学对65例LSCC进行了研究。前体半胱天冬酶-3的表达在16例(24.6%)中缺失或较弱,21例(32.3%)中为中度,28例(43.1%)中为强阳性。不同水平前体半胱天冬酶-3的生存曲线不同,但差异无统计学意义。通过对活化的半胱天冬酶-3阳性细胞进行定量来确定凋亡指数(AI)。AI范围为0.2%至9.4%,在不同水平的前体半胱天冬酶-3表达之间无差异。即使在前体半胱天冬酶-3表达被认为阴性的病例中,也发现了半胱天冬酶-3阳性的凋亡细胞。与声门肿瘤相比,声门上肿瘤的AI显著更高(P = 0.008),与高分化和中分化LSCC相比,低分化肿瘤的AI更高(P = 0.06)。尽管在LSCC的p53阳性组中前体半胱天冬酶-3表达有升高趋势,但未发现AI与p53表达之间存在相关性。我们的结果表明,凋亡中的关键执行性半胱天冬酶——前体半胱天冬酶-3的表达在一部分LSCC中下调,但这与通过活化的半胱天冬酶-3标记测量的凋亡活性降低无关。

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