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5-氨基酮戊酸介导的光动力诊断辅助经尿道膀胱肿瘤切除术期间的光动力治疗效果

Photodynamic Therapeutic Effect during 5-Aminolevulinic Acid-Mediated Photodynamic Diagnosis-Assisted Transurethral Resection of Bladder Tumors.

作者信息

Nishimura Nobutaka, Miyake Makito, Onishi Sayuri, Fujii Tomomi, Miyamoto Tatsuki, Tomizawa Mitsuru, Shimizu Takuto, Morizawa Yosuke, Hori Shunta, Gotoh Daisuke, Nakai Yasushi, Torimoto Kazumasa, Tanaka Nobumichi, Fujimoto Kiyohide

机构信息

Department of Urology Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.

Department of Diagnostic Pathology Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.

出版信息

Adv Urol. 2024 Jul 20;2024:7548001. doi: 10.1155/2024/7548001. eCollection 2024.

Abstract

BACKGROUND

Photodynamic diagnosis-assisted transurethral resection of bladder tumors (PDD-TURBT) enhances detection of elusive lesions compared to standard white light-transurethral resection of bladder tumors (WL-TURBT). If minimal light exposure during PDD-TURBT induces the accumulation of reactive oxygen species (ROS), potentially resulting in phototoxicity in small lesions, apoptosis may be triggered in residual small tumors, allowing them to escape resection. We investigated the hypothesis of a potential photodynamic therapeutic effect during PDD-TURBT.

METHODS AND MATERIALS

Our study, conducted between January 2016 and December 2020 at Nara Medical University Hospital, focused on a specific emphasis on ROS production. Immunohistochemical analysis for thymidine glycol and N -hexanoyl-lysine was performed on 69 patients who underwent 5-aminolevulinic acid-mediated PDD-TURBT and 28 patients who underwent WL-TURBT. Additionally, we incrementally applied the minimal irradiation energy to T24 and UM-UC-3 cells treated with 5-aminolevulinic acid using instruments similar to those used in PDD-TURBT and evaluated intracellular ROS production and phototoxicity.

RESULTS

Immunohistochemical analysis revealed a significant increase in production of thymidine glycol and N -hexanoyl-lysine within the PDD-TURBT group. In T24 and UM-UC-3 cells treated with 5-aminolevulinic acid and light exposure, immunofluorescent staining demonstrated a dose-dependent increase in intracellular ROS production. In addition, higher irradiation energy levels were associated with a greater increase in ROS production and phototoxicity, as well as more significant decrease in mitochondrial membrane potential.

CONCLUSION

Although the irradiation energy used in PDD-TURBT did not reach the levels commonly used in photodynamic therapy, our findings support the presence of a potential cytotoxic effect on bladder lesions during PDD-TURBT.

摘要

背景

与标准白光膀胱肿瘤经尿道切除术(WL-TURBT)相比,光动力诊断辅助膀胱肿瘤经尿道切除术(PDD-TURBT)能增强对难以捉摸的病变的检测。如果PDD-TURBT期间的最小光照暴露会诱导活性氧(ROS)的积累,可能导致小病变中的光毒性,那么残余小肿瘤中可能会触发细胞凋亡,从而使其逃脱切除。我们研究了PDD-TURBT期间潜在光动力治疗效果的假设。

方法和材料

我们的研究于2016年1月至2020年12月在奈良医科大学医院进行,特别关注ROS的产生。对69例行5-氨基酮戊酸介导的PDD-TURBT的患者和28例行WL-TURBT的患者进行了胸苷二醇和N-己酰赖氨酸的免疫组织化学分析。此外,我们使用类似于PDD-TURBT中使用的仪器,对用5-氨基酮戊酸处理的T24和UM-UC-3细胞逐步施加最小照射能量,并评估细胞内ROS的产生和光毒性。

结果

免疫组织化学分析显示,PDD-TURBT组中胸苷二醇和N-己酰赖氨酸的产生显著增加。在用5-氨基酮戊酸处理并暴露于光的T24和UM-UC-3细胞中,免疫荧光染色显示细胞内ROS产生呈剂量依赖性增加。此外,更高的照射能量水平与ROS产生和光毒性的更大增加以及线粒体膜电位的更显著降低相关。

结论

尽管PDD-TURBT中使用的照射能量未达到光动力治疗中常用的水平,但我们的研究结果支持PDD-TURBT期间对膀胱病变存在潜在的细胞毒性作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af25/11300098/89c1848e5f60/AU2024-7548001.001.jpg

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