Hayashi Y, Yoshida T O, Nishiwaki M, Matsuzawa E, Yicheng L, Ohta I
Dept. of Microbiology and Immunology, Hamamatsu University School of Medicine.
Gan To Kagaku Ryoho. 1998 Nov;25(13):2069-74.
Photodynamic therapy (PDT) is a treatment modality that utilizes a photosensitizing drug activated by laser generated light. PDT is effective for oncologic applications. Many cancer patients have undergone a hematoporphyrin derivative (HpD)-mediated PDT. The HpD showed a side effect causing prolonged cutaneous photosensitivity. But ATX-S10, a new photosensitizer, provides rapid plasma and tissue clearance, comparable photoactivation efficiency, and superior light absorption of visible red. In this study, the tumor rejection mechanisms of PDT using ATX-S10 on HeLa tumors in nude mice were investigated with morphological and fluorometric methods. The mice were intracutaneously inoculated with HeLa cells, 5 x 10(5) or 1 x 10(7) cells. When tumors grew to about 10-12 mm in diameter, mice were intraperitoneally administered ATX-S10, 30 mg/kg, and 2 hours later the ATX-S10 in tumors was indirectly measured by a fluorometric machine, PMA-10 (Hamamatsu Photonics K. K.) and the tumors were irradiated by Optical Parametric Oscillator (Hamamatsu Photonics K. K.) tuned to a wave length at 670 nm, 5 mJ/pulse, 100 J/tumor. Before and after the irradiation, the effective mechanisms of PDT with ATX-S10 were studied by histological and ultrastructural approaches. The results showed occlusive thrombi in the microvasculature of the tumors and tumor cell death. These occlusive thrombi were observed within one hour after PDT at both light and electron microscopy levels, and were more remarkable as time passed after PDT. Therefore, the morphological studies of PDT with ATX-S10 suggested that the rejection mechanisms occurred mainly as a result of the destructive changes of the microvasculature in the tumors first, and secondly or simultaneously, tumor cells were destroyed through necrosis, and finally the tumors were rejected.
光动力疗法（PDT）是一种利用由激光产生的光激活的光敏药物的治疗方式。PDT在肿瘤学应用中有效。许多癌症患者接受了血卟啉衍生物（HpD）介导的PDT。HpD显示出导致皮肤光敏性延长的副作用。但是一种新的光敏剂ATX-S10具有快速的血浆和组织清除率、相当的光激活效率以及对可见红光的卓越光吸收能力。在本研究中，使用形态学和荧光测定法研究了在裸鼠中使用ATX-S10进行PDT对HeLa肿瘤的肿瘤排斥机制。给小鼠皮内接种5×10⁵或1×10⁷个HeLa细胞。当肿瘤直径长到约10 - 12毫米时，给小鼠腹腔注射30毫克/千克的ATX-S10，2小时后用荧光测定仪PMA - 10（滨松光子学株式会社）间接测量肿瘤中的ATX-S10，并使用调谐到670纳米波长、5毫焦/脉冲、100焦/肿瘤的光学参量振荡器（滨松光子学株式会社）对肿瘤进行照射。在照射前后，通过组织学和超微结构方法研究了使用ATX-S10进行PDT的有效机制。结果显示肿瘤微血管中有闭塞性血栓形成以及肿瘤细胞死亡。在PDT后一小时内，在光学显微镜和电子显微镜水平均观察到这些闭塞性血栓，并且随着PDT后时间的推移更为显著。因此，对使用ATX-S10进行PDT的形态学研究表明，排斥机制主要首先是由于肿瘤微血管的破坏性变化而发生，其次或同时，肿瘤细胞通过坏死被破坏，最终肿瘤被排斥。
