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前列腺特异性膜抗原:当前及未来的应用

Prostate-specific membrane antigen: current and future utility.

作者信息

Gregorakis A K, Holmes E H, Murphy G P

机构信息

Pacific Northwest Cancer Foundation, Northwest Hospital, Seattle, WA 98125, USA.

出版信息

Semin Urol Oncol. 1998 Feb;16(1):2-12.

PMID:9508077
Abstract

Prostate cancer is the most common cancer and the second leading cause of cancer-related death among men. New prostatic markers are needed to increase diagnostic and prognostic effectiveness. One such new marker is prostate-specific membrane antigen (PSMA). PSMA is a highly prostate-restricted membrane glycoprotein that is expressed in normal prostatic epithelial cells and elevated in prostate cancers, especially in poorly differentiated, metastatic, and hormone refractory carcinomas. It has been measured in serum with immunocompetitive and Western blot assays, and its levels have been found to be correlated with the prediction of treatment failure and disease prognosis. Reverse transcriptase-polymerase chain reaction (RT-PCR) assays with primers specific for PSMA have been shown to be more effective than PSA-specific primers in detecting hematogenous circulating prostate cancer cells; however, no clear benefit in patient staging or utility as a predictor of clinical outcome or response to treatment has so far been obtained using RT-PCR methods. PSMA is currently utilized as an immunoscintigraphic target using the antibody conjugate CYT-356 (ProstaScint; Cytogen, Princeton, NJ) and has been shown to have clinical value, particularly in detecting occult prostate cancer. Another current application of PSMA is in immunotherapy of prostate cancer, in which promising results have been obtained in a phase I trial, and a phase II trial is underway. The research summarized in this article indicates that PSMA is an excellent target for diagnostic and therapeutic applications in prostate cancer.

摘要

前列腺癌是男性中最常见的癌症,也是癌症相关死亡的第二大主要原因。需要新的前列腺标志物来提高诊断和预后的有效性。前列腺特异性膜抗原(PSMA)就是这样一种新标志物。PSMA是一种高度局限于前列腺的膜糖蛋白,在正常前列腺上皮细胞中表达,在前列腺癌中升高,尤其是在低分化、转移性和激素难治性癌中。已经通过免疫竞争和蛋白质印迹法在血清中对其进行检测,并且发现其水平与治疗失败和疾病预后的预测相关。已证明,使用针对PSMA的引物进行逆转录聚合酶链反应(RT-PCR)检测在检测血行循环前列腺癌细胞方面比使用针对前列腺特异性抗原(PSA)的引物更有效;然而,到目前为止,使用RT-PCR方法在患者分期或作为临床结果或治疗反应预测指标的效用方面尚未获得明确益处。目前,PSMA被用作使用抗体偶联物CYT-356(ProstaScint;Cytogen,普林斯顿,新泽西州)的免疫闪烁显像靶点,并且已显示具有临床价值,特别是在检测隐匿性前列腺癌方面。PSMA的另一个当前应用是在前列腺癌免疫治疗中,在一项I期试验中已取得了有前景的结果,并且一项II期试验正在进行中。本文总结的研究表明,PSMA是前列腺癌诊断和治疗应用的极佳靶点。

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