St. Olavs University Hospital Trondheim, Department of Surgery, N-7006 Trondheim, Norway.
J Biomed Opt. 2011 Feb;16(2):028001. doi: 10.1117/1.3536536.
Orthotopic bladder cancer model in rats mimics human bladder cancer with respect to urothelial tumorigenesis and progression. Utilizing this model at pT1 (superficial stage), we analyze the tissue responses to hexyl 5-aminolevulinate-induced photodynamic therapy (HAL-PDT). In comparison to untreated rats, HAL-PDT causes little change in tumor-free rat bladder but induces inflammatory changes with increased lymphocytes and mononuclear cell infiltration in rat bladders with tumor. Immunohistochemistry reveals that HAL-PDT is without effect on proliferating cell nuclear antigen expression within the tumor and increases caspase-3 expression in both normal urothelium and the tumor. Transmission electron microscopy reveals severe mitochondrial damage, formations of apoptotic bodies, vacuoles, and lipofuscin bodies, but no microvillus-formed niches in HAL-PDT-treated bladder cancer rats. Bioinformatics analysis of the gene expression profile indicates an activation of T-cell receptor signaling pathway in bladder cancer rats without PDT. HAL-PDT increases the expression of CD3 and CD45RA in the tumor (determined by immunohistochemistry). We suggest that pathways of action of HAL-PDT may include, at least, activations of mitochondrial apoptosis and autophagy, breakdown of cancer stem cell niches, and importantly, enhancement of T-cell activation.
原位膀胱癌大鼠模型在尿路上皮肿瘤发生和进展方面模拟人类膀胱癌。利用该模型在 pT1（表浅阶段），我们分析了组织对己基 5-氨基酮戊酸诱导的光动力疗法（HAL-PDT）的反应。与未治疗的大鼠相比，HAL-PDT 对无肿瘤的大鼠膀胱几乎没有影响，但在有肿瘤的大鼠膀胱中引起炎症变化，淋巴细胞和单核细胞浸润增加。免疫组织化学显示，HAL-PDT 对肿瘤内增殖细胞核抗原的表达没有影响，并增加了正常尿路上皮和肿瘤中 caspase-3 的表达。透射电子显微镜显示严重的线粒体损伤、凋亡小体、空泡和脂褐素体的形成，但在 HAL-PDT 治疗的膀胱癌大鼠中没有微绒毛形成的龛位。基因表达谱的生物信息学分析表明，在没有 PDT 的膀胱癌大鼠中，T 细胞受体信号通路被激活。HAL-PDT 增加了肿瘤中 CD3 和 CD45RA 的表达（通过免疫组织化学确定）。我们认为，HAL-PDT 的作用途径至少包括线粒体凋亡和自噬的激活、癌症干细胞龛位的破坏，以及重要的 T 细胞激活的增强。
