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MN/CA IX/G250作为肾细胞癌免疫治疗的潜在靶点。

MN/CA IX/G250 as a potential target for immunotherapy of renal cell carcinomas.

作者信息

Uemura H, Nakagawa Y, Yoshida K, Saga S, Yoshikawa K, Hirao Y, Oosterwijk E

机构信息

Department of Urology, Nara Medical University, Kashihara, Japan.

出版信息

Br J Cancer. 1999 Oct;81(4):741-6. doi: 10.1038/sj.bjc.6690757.

Abstract

The monoclonal antibody G250 (mAbG250) raised against a human renal cell carcinoma (RCC) has been shown to react with a large number of RCCs. Recently, G250 antigen was isolated and found to be homologous to the MN/CA9 gene originally identified in HeLa cells. To determine whether G250 antigen (MN/CA IX/G250) could be a potential therapeutic target and a tumour marker, a total of 147 cases of RCC were investigated immunohistochemically as well as by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. In addition, total RNAs extracted from patients' peripheral blood samples were analysed for MN/CA9/G250 mRNA signals. Immunohistochemistry demonstrated strong expression in 128/147 (87.1%) of RCCs, in contrast to the lack of expression observed in normal tissues. RT-PCR analyses of frozen specimens resulted in the clear detection of MN/CA9/G250 mRNA signals in 137/147 (93.2%), and despite subtle differences the results were almost identical to those for immunohistochemistry. Although high-grade and -stage tumours exhibited significantly lower expression than low-grade and -stage tumours, a large proportion of tumours expressed MN/G250 protein as well as mRNA. RT-PCR analysis of patients' blood samples revealed the presence of circulating MN/CA9/G250 expressing cells. These findings suggest that this antigen may be a potential therapeutic target as well as diagnostic marker for RCCs.

摘要

针对人肾细胞癌(RCC)产生的单克隆抗体G250(mAbG250)已被证明可与大量肾细胞癌发生反应。最近,G250抗原被分离出来,发现与最初在HeLa细胞中鉴定的MN/CA9基因同源。为了确定G250抗原(MN/CA IX/G250)是否可能是潜在的治疗靶点和肿瘤标志物,对147例肾细胞癌患者进行了免疫组织化学以及逆转录聚合酶链反应(RT-PCR)分析。此外,还对从患者外周血样本中提取的总RNA进行了MN/CA9/G250 mRNA信号分析。免疫组织化学显示,147例肾细胞癌中有128例(87.1%)呈强表达,而在正常组织中未观察到表达。对冷冻标本进行的RT-PCR分析结果显示,147例中有137例(93.2%)能清晰检测到MN/CA9/G250 mRNA信号,尽管存在细微差异,但结果与免疫组织化学结果几乎相同。尽管高级别和高分期肿瘤的表达明显低于低级别和低分期肿瘤,但仍有很大比例的肿瘤表达MN/G250蛋白和mRNA。对患者血液样本进行的RT-PCR分析显示存在循环表达MN/CA9/G250的细胞。这些发现表明,这种抗原可能是肾细胞癌潜在的治疗靶点和诊断标志物。

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