Basics of the photodynamic therapy (PDT) of bladder carcinoma using Tetrahydroporphyrin-Tetratosylate (THPTS)

使用四氢卟啉-四甲苯磺酸盐 (THPTS) 进行膀胱癌光动力疗法 (PDT) 的基础知识

• 批准号: 227823537
• 负责人: Professor Dr. Jochen Neuhaus
• 金额: --
• 依托单位: Institut für Pathologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/227823537?language=en
• 关键词: Basics; photodynamic; therapy; PDT; bladder

Bladder carcinoma is the third most frequent tumour in Germany. The estimated mortality rate is 6.4%. The therapy of the bladder carcinoma depends on the tumour grade and invasiveness. Surgical interventions are transurethral resection of superficial tumours (TURB) and radical cystectomy in case of advanced, invasive stages. In support of the TURB, photodynamic diagnosis (PDD) using aminolevulinate or hexaminolevulinate has been established. PDD has improved the detection and resection of visually unsuspicious superficial urothelial tumours. Those substances have also been used for photodynamic therapy (PDT). However, due to insufficient tissue penetration of excitation light and due to toxic side effects caused by high irradiation, the results were disappointing.Tetrahydroporphyrin-Tetratosylate (THPTS) is the first photosensitizer with photo-physical properties and high absorption at infrared wavelength of 760nm, which might be suitable to treat superficial and infiltrating tumours by PDT. Prerequisite for successful establishment of THPTS-PDT is the proof of toxicological safety and efficiency in an animal model and the elucidation of the mode of action in vitro. We want to address those questions using a rat bladder carcinoma model and cultured bladder carcinoma cell lines. Bladder carcinoma will be induced in the rat bladder by instillation of AY27 rat bladder carcinoma cells. The established bladder tumours will be treated by THPTS-PDT. The safety of THPTS-PDT will be examined in animal model by dose range finding experiments including evaluation of possible injury of healthy bladder tissue. Treatment efficiency will be verified by histological examination. The mode of action of THPTS-PDT will be examined in vitro using cultured rat cells, human normal bladder cells and bladder carcinoma cell lines. We will apply confocal microscopy, immunocytochemistry, cell vitality and apoptosis assays, and gene expression analysis.

膀胱癌是德国第三常见的肿瘤。估计死亡率为6.4%。膀胱癌的治疗取决于肿瘤的分级和侵袭性。手术干预是经尿道浅表肿瘤切除术（TURB）和根治性膀胱癌的情况下，先进的，侵入性阶段。为了支持TURB，已经建立了使用氨基乙酰丙酸或六氨基乙酰丙酸的光动力学诊断（PDD）。PDD改善了视觉上不可疑的浅表尿路上皮肿瘤的检测和切除。这些物质也被用于光动力疗法（PDT）。四氢卟啉-四对甲苯磺酸盐（Tetrahydroporphyrin-Tetratosylate，THPTS）是第一种具有光物理性质的光敏剂，在760 nm红外波长处有很高的吸收，可能适用于PDT治疗浅表性和浸润性肿瘤。成功建立THPTS-PDT的先决条件是在动物模型中证明毒理学安全性和有效性，并阐明体外作用模式。我们想用大鼠膀胱癌模型和培养的膀胱癌细胞系来解决这些问题。通过滴注AY 27大鼠膀胱癌细胞将在大鼠膀胱中诱导膀胱癌。建立的膀胱肿瘤将通过THPTS-PDT治疗。THPTS-PDT的安全性将在动物模型中通过剂量范围探索实验进行检查，包括评估健康膀胱组织的可能损伤。将通过组织学检查验证治疗效率。将使用培养的大鼠细胞、人正常膀胱细胞和膀胱癌细胞系在体外检查THPTS-PDT的作用模式。我们将应用共聚焦显微镜，免疫细胞化学，细胞活力和凋亡测定，和基因表达分析。