Division of Medical Sciences, National Cancer Centre Singapore, Singapore.
Urol Oncol. 2012 Sep;30(5):624-34. doi: 10.1016/j.urolonc.2010.07.006. Epub 2010 Oct 8.
To elucidate the mechanism behind selective uptake of hypericin in bladder cancer after intravesical instillation for photodynamic diagnosis of urothelial cell carcinoma of bladder.
Clinical studies were done on a series of 60 bladder cancer biopsies obtained from 28 patients who received intravesical instillations with 8 μM hypericin. Serial 5 μm cryosections were cut from 43 biopsies, and expression of the E-cadherin and associated catenins were determined using immunohistochemical and immunofluorescence staining. Hypericin was assessed using fluorescence confocal laser scanning microscopy. In addition, mRNA expression of these cell-adhesion molecules was analyzed in 17 biopsies using reverse transcription-PCR.
Increased variability in the expression of E-cadherin and associated molecules was found in high-grade, advanced stage bladder carcinoma. An inverse association was found between immunoreactivity for E-cadherin, β- and γ-catenin, and both stage and grade of cancer (P < 0.05). A positive association was observed between the hypericin fluorescence and tumor grade. There was a significant down-regulation of E-cadherin and β-catenin mRNA in grade 2 and 3 tumors. Although a small sample size was studied, it provided sufficient proof to support the hypothesis that altered expression of cell adhesion molecules would lead to preferential hypericin uptake in urothelial cell carcinoma.
Our study has unraveled one of the many factors contributing to the selective uptake of hypericin in bladder cancer. We have thus identified the effects of alteration of E-cadherin-catenin complex and transformed intercellular junction in the modified paracellular uptake of hypericin that provides the rationale for using this photosensitizer in photodynamic diagnosis of bladder carcinoma.
阐明膀胱癌经膀胱内灌注后摄取金丝桃素用于膀胱癌尿路上皮细胞癌光动力诊断的机制。
对 28 例接受 8 μM 金丝桃素膀胱内灌注的患者的 60 例膀胱癌活检进行了临床研究。从 43 例活检中连续切取 5μm 冷冻切片，使用免疫组织化学和免疫荧光染色检测 E-钙黏蛋白及其相关连接蛋白的表达。使用荧光共聚焦激光扫描显微镜评估金丝桃素。此外，使用逆转录-PCR 分析了 17 例活检中这些细胞黏附分子的 mRNA 表达。
在高级别、晚期膀胱癌中发现 E-钙黏蛋白及其相关分子的表达变异性增加。E-钙黏蛋白、β-和γ-连环蛋白的免疫反应性与癌症的分期和分级呈负相关（P<0.05）。金丝桃素荧光与肿瘤分级呈正相关。E-钙黏蛋白和β-连环蛋白 mRNA 在 2 级和 3 级肿瘤中显著下调。尽管样本量较小，但提供了足够的证据支持以下假说，即细胞黏附分子表达的改变将导致尿路上皮细胞癌中金丝桃素的选择性摄取。
我们的研究揭示了导致膀胱癌中金丝桃素选择性摄取的众多因素之一。因此，我们确定了 E-钙黏蛋白-连环蛋白复合物改变和细胞间连接转化对金丝桃素经细胞旁途径摄取的影响，为使用这种光敏剂进行膀胱癌光动力诊断提供了依据。
