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血清前列腺特异性膜抗原的检测,一种前列腺癌新的预后标志物。

Measurement of serum prostate-specific membrane antigen, a new prognostic marker for prostate cancer.

作者信息

Murphy G P, Kenny G M, Ragde H, Wolfert R L, Boynton A L, Holmes E H, Misrock S L, Bartsch G, Klocker H, Pointner J, Reissigl A, McLeod D G, Douglas T, Morgan T, Gilbaugh J

机构信息

Pacific Northwest Cancer Foundation, Cancer Research Division, Northwest Hospital, Seattle, Washington 98125, USA.

出版信息

Urology. 1998 May;51(5A Suppl):89-97. doi: 10.1016/s0090-4295(98)00082-x.

DOI:10.1016/s0090-4295(98)00082-x
PMID:9610563
Abstract

OBJECTIVES

To describe current results with Western blot assay for prostate specific membrane antigen (PSMA) using 7E11.C5 antibody and the development of an additional antibody measurement for PSMA by a new sandwich immunoassay.

METHODS

A population of patients from a screening group, from a difficult diagnostic group, from a pre- and postoperative radical prostatectomy group, and from a group with metastatic disease followed for a serial period, provided the serum values for a prospective assessment of PSMA by Western blot assay. A new monoclonal antibody was sought, reacting to the C-terminal region of PSMA in order to develop a sandwich radioimmunoassay.

RESULTS

PSMA values in screened patients correlate with the more advanced stage of the cancers determined. In postprostatectomy patients, the PSMA value corresponds more with preoperative values and with the values of those with a poor clinical course. In difficult diagnostic cases, the PSMA value is increased, specifically in hormone-refractory cases and particularly in those cases judged by other criteria, such as the National Prostatic Cancer Project, to be in clinical progression compared with those judged to be in clinical remission. The level of PSMA value appears to be independent of homogeneous tumor volume and to be more related to that of prior hormone treatment, or to where prostate cancer cells can be documented to be outside the prostate. A new monoclonal antibody, 3F5.4G6, reacts with the extracellular domain of PSMA near the C-terminal region. This is in contrast to the previously measured antibody 7E11.C5, which reacts with an N-terminal epitope. 3F5.4G6 recognizes the same PSMA protein as does 7E11.C5. The epitopes are essentially at opposite ends of the molecule. The 3F5.4G6 antibody reacts with the LNCaP line but not with DU145, or PC3. These two antibodies to PSMA are well suited for use in a new sandwich immunoassay.

CONCLUSIONS

PSMA provides a prostatic cancer serum test by using Western blot, which suggests a clinical prognostic value not seen with other markers. New antibodies, such as 3F5.4G6, reacting with the extracellular domain of PSMA combined with 7E11.C5, appear to offer an opportunity for a new sandwich immunoassay.

摘要

目的

描述使用7E11.C5抗体通过蛋白质印迹法检测前列腺特异性膜抗原(PSMA)的当前结果,以及开发一种通过新型夹心免疫测定法对PSMA进行额外抗体检测的方法。

方法

来自筛查组、疑难诊断组、前列腺癌根治术术前和术后组以及患有转移性疾病且随访了一段时间的患者群体,提供血清值用于通过蛋白质印迹法对PSMA进行前瞻性评估。寻找一种新的单克隆抗体,使其与PSMA的C末端区域反应,以开发一种夹心放射免疫测定法。

结果

筛查患者中的PSMA值与所确定的癌症更晚期阶段相关。在前列腺切除术后患者中,PSMA值与术前值以及临床病程较差患者的值更相符。在疑难诊断病例中,PSMA值升高,特别是在激素难治性病例中,尤其是那些根据其他标准(如国家前列腺癌项目)判断为处于临床进展期的病例,与判断为临床缓解期的病例相比。PSMA值水平似乎与肿瘤均匀体积无关,而更多地与先前的激素治疗水平相关,或者与前列腺癌细胞可被记录在前列腺外的位置相关。一种新的单克隆抗体3F5.4G6与PSMA靠近C末端区域的细胞外结构域反应。这与先前检测的抗体7E11.C5形成对比,7E11.C5与N末端表位反应。3F5.4G6与7E11.C5识别相同的PSMA蛋白。表位基本上位于分子的相对两端。3F5.4G6抗体与LNCaP细胞系反应,但不与DU145或PC3反应。这两种针对PSMA的抗体非常适合用于新型夹心免疫测定法。

结论

PSMA通过蛋白质印迹法提供了一种前列腺癌血清检测方法,这表明其具有其他标志物未见的临床预后价值。新的抗体,如与PSMA细胞外结构域反应的3F5.4G6与7E11.C5相结合,似乎为新型夹心免疫测定法提供了机会。

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