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5-氨基乙酰丙酸在兽医学光动力检测及光动力治疗中的疗效

Efficacy of 5-Aminolevulinic Acid in Photodynamic Detection and Photodynamic Therapy in Veterinary Medicine.

作者信息

Osaki Tomohiro, Yokoe Inoru, Sunden Yuji, Ota Urara, Ichikawa Tomoki, Imazato Hideo, Ishii Takuya, Takahashi Kiwamu, Ishizuka Masahiro, Tanaka Tohru, Li Liming, Yamashita Masamichi, Murahata Yusuke, Tsuka Takeshi, Azuma Kazuo, Ito Norihiko, Imagawa Tomohiro, Okamoto Yoshiharu

机构信息

Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, 4-101 Koyama-Minami, Tottori 680-8553, Japan.

SBI Pharmaceuticals Co., Ltd., Tokyo 106-6020, Japan.

出版信息

Cancers (Basel). 2019 Apr 7;11(4):495. doi: 10.3390/cancers11040495.

Abstract

5-Aminolevulinic acid (5-ALA), a commonly used photosensitizer in photodynamic detection (PDD) and therapy (PDT), is converted in situ to the established photosensitizer protoporphyrin IX (PpIX) via the heme biosynthetic pathway. To extend 5-ALA-PDT application, we evaluated the PpIX fluorescence induced by exogenous 5-ALA in various veterinary tumors and treated canine and feline tumors. 5-ALA-PDD sensitivity and specificity in the whole sample group for dogs and cats combined were 89.5 and 50%, respectively. Notably, some small tumors disappeared upon 5-ALA-PDT. Although single PDT application was not curative, repeated PDT+/-chemotherapy achieved long-term tumor control. We analyzed the relationship between intracellular PpIX concentration and 5-ALA-PDT in vitro cytotoxicity using various primary tumor cells and determined the correlation between intracellular PpIX concentration and 5-ALA transporter and metabolic enzyme mRNA expression levels. 5-ALA-PDT cytotoxicity in vitro correlated with intracellular PpIX concentration in carcinomas. Ferrochelatase mRNA expression levels strongly negatively correlated with PpIX accumulation, representing the first report of a correlation between mRNA expression related to PpIX accumulation and PpIX concentration in canine tumor cells. Our findings suggested that the results of 5-ALA-PDD might be predictive for 5-ALA-PDT therapeutic effects for carcinomas, with 5-ALA-PDT plus chemotherapy potentially increasing the probability of tumor control in veterinary medicine.

摘要

5-氨基酮戊酸(5-ALA)是光动力检测(PDD)和治疗(PDT)中常用的光敏剂,它通过血红素生物合成途径原位转化为已确定的光敏剂原卟啉IX(PpIX)。为了扩展5-ALA-PDT的应用,我们评估了外源性5-ALA在各种兽医肿瘤中诱导的PpIX荧光,并对犬猫肿瘤进行了治疗。犬猫全样本组中5-ALA-PDD的敏感性和特异性分别为89.5%和50%。值得注意的是,一些小肿瘤在5-ALA-PDT治疗后消失。虽然单次PDT应用不能治愈,但重复的PDT+/-化疗实现了长期的肿瘤控制。我们使用各种原发性肿瘤细胞分析了细胞内PpIX浓度与5-ALA-PDT体外细胞毒性之间的关系,并确定了细胞内PpIX浓度与5-ALA转运体和代谢酶mRNA表达水平之间的相关性。5-ALA-PDT体外细胞毒性与癌组织中的细胞内PpIX浓度相关。亚铁螯合酶mRNA表达水平与PpIX积累呈强烈负相关,这是首次报道犬肿瘤细胞中与PpIX积累相关的mRNA表达与PpIX浓度之间的相关性。我们的研究结果表明,5-ALA-PDD的结果可能对癌组织的5-ALA-PDT治疗效果具有预测性,5-ALA-PDT联合化疗可能会增加兽医学中肿瘤控制的概率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8060/6520946/2c86c0f4185f/cancers-11-00495-g001.jpg

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