Tumor destruction and kinetics of tumor cell death in two experimental mouse tumors following photodynamic therapy.
Tumor destruction and kinetics of tumor cell death in two experimental mouse tumors following photodynamic therapy.
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发表时间：
1985-02
期刊：
影响因子：
11.2
通讯作者：
B. Henderson;S. Waldow;T. Mang;W. Potter;P. B. Malone;T. Dougherty
中科院分区：
文献类型：
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作者：
B. Henderson;S. Waldow;T. Mang;W. Potter;P. B. Malone;T. Dougherty
在EMT-6和RIF实验小鼠肿瘤系统中研究了光动力疗法（PDT）对肿瘤生长以及对肿瘤细胞存活的体外和体内作用。在体外，当与卟啉（25微克/毫升，二血卟啉醚）孵育并随后给予分级剂量的光时，RIF细胞对PDT比EMT-6细胞更敏感。在体内，两种肿瘤类型均对PDT（EMT-6，二血卟啉醚，7.5 mg/kg; RIF，二血卟啉醚，10 mg/kg; 24小时后均用630 nm/cm 2的135 J光照射）有反应，伴有严重的血管破裂和随后的肿瘤块消失。然而，EMT-6肿瘤的治愈率为90%，而RIF肿瘤的治愈率为0%。将光剂量提高到200 J/cm 2导致EMT-6肿瘤100%治愈，伴有周围组织损伤，RIF肿瘤治愈率为13%。使用体外集落形成测定评估体内PDT后的肿瘤细胞集落形成性。在这两种肿瘤中，发现如果在治疗完成后立即切除肿瘤组织并重新组织，则几乎不受PDT的影响。这表明PDT对肿瘤细胞的直接作用不足以降低肿瘤克隆形成性，即使在导致总体宏观肿瘤破坏的剂量下也是如此。在PDT后肿瘤保持在原位并且肿瘤消退延迟不同的时间长度（1至24小时）的情况下，肿瘤细胞死亡迅速且进行性地发生，表明肿瘤细胞损伤仅在细胞在治疗后保持暴露于原位环境的情况下表达。两种肿瘤类型的肿瘤细胞死亡的动力学和程度非常相似，尽管它们的治愈率不同。PDT后4小时肿瘤克隆形成的减少与缺氧相同时间段的肿瘤克隆形成的减少密切匹配，这意味着导致肿瘤破坏的主要因素之一可能是肿瘤循环的损伤和治疗诱导的肿瘤生理学变化的后果。
The effect of photodynamic therapy (PDT) on tumor growth as well as on tumor cell survival in vitro and in vivo was studied in the EMT-6 and RIF experimental mouse tumor systems. In vitro, RIF cells were more sensitive towards PDT than were EMT-6 cells when incubated with porphyrin (25 micrograms/ml, dihematoporphyrin ether) and subsequently given graded doses of light. In vivo, both tumor types responded to PDT (EMT-6, dihematoporphyrin ether, 7.5 mg/kg; RIF, dihematoporphyrin ether, 10 mg/kg; both followed 24 hr later by 135 J of light at 630 nm/sq cm) with severe vascular disruption and subsequent disappearance of tumor bulk. However, whereas the cure rate for EMT-6 tumors was 90%, it was 0% for RIF tumors. Raising the light dose to 200 J/sq cm resulted in 100% cures for EMT-6 tumors accompanied by damage to the surrounding tissues and 13% cures for RIF tumors. Tumor cell clonogenicity following PDT in vivo was assessed using the in vitro colony formation assay. In both tumors, it was found to be nearly unaffected by PDT if the tumor tissue was excised and explanted immediately following completion of treatment. This indicates that the effect of PDT on tumor cells directly was not sufficient to decrease tumor clonogenicity even at doses which led to total macroscopic tumor destruction. Where the tumors remained in situ following PDT and explantation was delayed for varying lengths of time (1 to 24 hr), tumor cell death occurred rapidly and progressively, indicating that tumor cell damage was expressed only if the cells remained exposed to the in situ environment after treatment. The kinetics and extent of tumor cell death were very similar for both tumor types despite their difference in cure rates. The reduction in tumor clonogenicity at 4 hr post-PDT closely matched that of tumor deprived of oxygen for the same period of time, implying that one of the major factors contributing to tumor destruction may be damage of the tumor circulation and the consequences of treatment-induced changes in tumor physiology.