MECHANISM OF TUMOR DESTRUCTION FOLLOWING PHOTODYNAMIC THERAPY WITH HEMATOPORPHYRIN DERIVATIVE, CHLORIN, AND PHTHALOCYANINE
MECHANISM OF TUMOR DESTRUCTION FOLLOWING PHOTODYNAMIC THERAPY WITH HEMATOPORPHYRIN DERIVATIVE, CHLORIN, AND PHTHALOCYANINE
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DOI：
10.1093/jnci/80.20.1599
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发表时间：
1988-12-21
影响因子：
10.3
通讯作者：
BERNS, MW
中科院分区：
文献类型：
--
作者：
NELSON, JS;LIAW, LH;BERNS, MW
在光镜和电镜下观察光动力治疗对肿瘤微血管的影响。EMT-6肿瘤的BALB/c小鼠接受血卟啉衍生物、氯或酞菁的ip注射，24小时后，在每种光敏剂适当的治疗波长下，以100 J/cm2的光治疗肿瘤。分别于治疗后0、30分钟、1小时、2、4、6、8、12、16和24小时处死动物并切除肿瘤。结果表明，对于所有三种致敏剂，光动力疗法导致肿瘤组织快速坏死的效果不是直接杀死肿瘤细胞的结果，而是继发于肿瘤微血管的破坏。第一个可观察到的破坏迹象发生在肿瘤毛细血管壁的内皮下区。该区域由致密的胶原纤维和其他结缔组织成分组成，在光疗后的最初几个小时内被破坏。然而，与氯和酞菁相比，血卟啉衍生物在该区域的超微结构变化是不同的。光敏剂与该区域元素的结合以及由于腔内压力增加而改变的通透性和通过内皮细胞层的运输可能是肿瘤破坏的关键特征。
The effect of photodynamic therapy on the tumor microvasculature in the first few hours after treatment was studied at the light and electron microscopy levels. BALB/c mice with EMT-6 tumor received ip injections of hematoporphyrin derivative, chlorin, or phthalocyanine, and 24 hours later, the tumors were treated with light at 100 J/cm2 at the appropriate therapeutic wavelength for each photosensitizer. Animals were killed and their tumors removed at time 0, 30 minutes, 1 hour, and 2, 4, 6, 8, 12, 16, and 24 hours after treatment. The results indicate that for all three sensitizers the effects of photodynamic therapy leading to rapid necrosis of tumor tissue are not the result of direct tumor cell kill but are secondary to destruction of the tumor microvasculature. The first observable signs of destruction occur in the subendothelial zone of the tumor capillary wall. This zone, composed of dense collagen fibers and other connective tissue elements, is destroyed in the first few hours after phototherapy. However, the ultrastructural changes seen in this zone are different for the hematoporphyrin derivative, compared with chlorin and phthalocyanine. Binding of photosensitizers to the elements in this zone as well as altered permeability and transport through the endothelial cell layer because of the increased intraluminal pressure may be key features of tumor destruction.