Onodera Mikoto, Kitahara Shuji, Sato Yasuto, Kawamata Takakazu, Muragaki Yoshihiro, Masamune Ken
Faculty of Advanced Techno-Surgery (FATS), Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shinjuku, Tokyo 162-8666, Japan.
Department of Pharmacy, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shinjuku, Tokyo 162-8666, Japan.
Pharmaceuticals (Basel). 2025 Apr 16;18(4):583. doi: 10.3390/ph18040583.
Although extensive resection improves the prognosis of gliomas, it risks impairing critical brain functions. Photodynamic therapy (PDT) utilizing talaporfin sodium (TS) targets tumor cells upon light activation. Despite its approval in Japan, TS application remains restricted, and factors influencing its efficacy are unclear. We aimed to identify TS efficacy determinants to optimize treatment outcomes. Data from 171 patients with grade 4 glioma who underwent surgery and PDT at Tokyo Women's Medical University Hospital between January 2017 and March 2024 were retrospectively analyzed. Clinical variables evaluated included age, sex, genotype, Karnofsky Performance Status (KPS), serum albumin (Alb) levels, MIB-1 expression levels, and medication history. TS concentrations in tumor tissues were quantitatively assessed in 82 patients (41 primary, 41 recurrent). Survival outcomes were analyzed. RNA-seq was performed on the three highest and three lowest TS concentration samples with significant TS concentration variations to investigate corresponding gene expression changes. Multivariate analysis identified KPS (hazard ratio [95% confidence interval]: 0.96 [0.93-0.99], = 0.01) and Alb (3.68 [1.05-13.76], = 0.047) as independent prognostic factors. In recurrent cases, higher TS concentrations were significantly associated with improved survival ( = 0.0454). RNA-seq analysis indicated decreased expression of and genes in samples with lower TS concentrations, suggesting potential resistance mechanisms. TS concentration is a critical determinant of PDT efficacy, especially in recurrent glioma, highlighting its prognostic significance. Alb may affect treatment outcomes by mediating TS binding. RNA-seq findings imply that low TS concentrations may suppress immune and stress response-related genes, potentially diminishing PDT sensitivity.
尽管广泛切除可改善胶质瘤的预后，但有损害关键脑功能的风险。利用替莫泊芬钠（TS）的光动力疗法（PDT）在光激活后靶向肿瘤细胞。尽管TS在日本已获批准，但其应用仍受到限制，且影响其疗效的因素尚不清楚。我们旨在确定TS疗效的决定因素，以优化治疗效果。对2017年1月至2024年3月期间在东京女子医科大学医院接受手术和PDT的171例4级胶质瘤患者的数据进行了回顾性分析。评估的临床变量包括年龄、性别、基因型、卡氏功能状态（KPS）、血清白蛋白（Alb）水平、MIB-1表达水平和用药史。对82例患者（41例原发性，41例复发性）的肿瘤组织中的TS浓度进行了定量评估。分析了生存结果。对TS浓度有显著差异的三个最高和三个最低TS浓度样本进行RNA测序，以研究相应的基因表达变化。多变量分析确定KPS（风险比[95%置信区间]：0.96[0.93-0.99]，P = 0.01）和Alb（3.68[1.05-13.76]，P = 0.047）为独立的预后因素。在复发性病例中，较高的TS浓度与生存率提高显著相关（P = 0.0454）。RNA测序分析表明，TS浓度较低的样本中某些基因的表达降低，提示可能存在耐药机制。TS浓度是PDT疗效的关键决定因素，尤其是在复发性胶质瘤中，突出了其预后意义。Alb可能通过介导TS结合来影响治疗效果。RNA测序结果表明，低TS浓度可能抑制免疫和应激反应相关基因，从而可能降低PDT敏感性。
