Rauen Katherine A, Sudilovsky Daniel, Le Jason L, Chew Karen L, Hann Byron, Weinberg Vivian, Schmitt Lars D, McCormick Frank
Department of Pediatrics, University of California, San Francisco, California 94115, USA.
Cancer Res. 2002 Jul 1;62(13):3812-8.
Adenovirus-based gene therapy may provide an alternative mode of treatment for prostate cancer, especially for late-stage and androgen-independent disease for which there is currently no effective treatment. Efficient adenovirus infection of target cells depends upon the presence of the coxsackie adenovirus cell surface receptor, CAR, which is the primary receptor for group C adenoviruses and is important for the attachment of adenovirus to the cell membrane. To evaluate the potential efficacy of adenoviral therapy for prostate cancer, we evaluated CAR expression in normal prostate tissue and in prostate carcinoma of increasing Gleason grades in paraffin-embedded, archival tissues using a polyclonal antibody raised against human CAR. Immunohistochemical analysis of benign prostate epithelia demonstrated intense luminal and lateral cell membrane staining. There was a statistically significant difference in CAR membrane expression with respect to Gleason score. In addition, metastatic prostate specimens demonstrated strong membrane staining for CAR. Adenovirus therapy may, therefore, provide an alternate modality in the treatment of prostate cancer and may be especially efficacious in the treatment of metastatic disease.
基于腺病毒的基因疗法可能为前列腺癌提供一种替代治疗方式,特别是对于晚期和雄激素非依赖性疾病,目前尚无有效治疗方法。腺病毒对靶细胞的有效感染取决于柯萨奇腺病毒细胞表面受体(CAR)的存在,CAR是C组腺病毒的主要受体,对腺病毒附着于细胞膜很重要。为了评估腺病毒疗法对前列腺癌的潜在疗效,我们使用针对人CAR产生的多克隆抗体,在石蜡包埋的存档组织中评估了正常前列腺组织和不同Gleason分级的前列腺癌组织中CAR的表达。良性前列腺上皮的免疫组织化学分析显示管腔和侧细胞膜有强烈染色。CAR膜表达在Gleason评分方面存在统计学上的显著差异。此外,转移性前列腺标本显示CAR有强烈的膜染色。因此,腺病毒疗法可能为前列腺癌治疗提供另一种方式,并且在转移性疾病的治疗中可能特别有效。