Photodynamic therapy of human lung cancer xenografts in mice.

Photodynamic therapy of human lung cancer xenografts in mice.
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DOI:
10.1016/j.jss.2015.07.024
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发表时间:
2016-01
期刊:
The Journal of surgical research
影响因子:
--
通讯作者:
Pandey R
Pandey R
中科院分区:
其他
文献类型:
--
作者:
Nwogu C;Pera P;Bshara W;Attwood K;Pandey R

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有必要开发新的治疗非小细胞肺癌(NSCLC)的方法。光动力疗法已成功用于非小细胞肺癌的支气管内姑息治疗,其在疾病早期阶段的作用正在探索中。我们假设一种新型光敏剂PS1在治疗小鼠人类肺癌异种移植物方面比标准药物Porfimer钠(Photofrin®或PFII)更有效。患者来源的非小细胞肺癌异种移植物在SCID小鼠皮下建立。两组5只小鼠分别注射PS1[3-(1′-m-碘苯氧基)乙基-3- devinylpyrophophrbie -a]、叶绿素-a衍生物或PFII(纯化版血卟啉衍生物),然后用非热激光处理。4只小鼠用不含光敏剂的激光处理,6只小鼠不作任何处理。然后观察所有小鼠的肿瘤生长情况。使用标准Kaplan-Meier方法和log-rank检验评估肿瘤生长终点(time-to-1000mm3)。肿瘤H&E和Caspase3染色评价坏死和凋亡情况。对照组、纯光照组、PF II组和PS1组的中位时间分别为12、12、26和52天。肿瘤生长终点与治疗有显著相关性(p<0.05)。H&E染色显示坏死<1%、0%、67%和80%,Caspase3阳性分别为2%、<1%、17%和39%。与其他处理组相比,经PS1处理的小鼠肿瘤再生时间更长,肿瘤坏死和细胞凋亡更多。因此,在这项临床前试验中,新型光敏剂PS1被证明比Porfimer钠更有效。
There is a need to develop novel therapies for non-small cell lung cancer (NSCLC). Photodynamic therapy has been used successfully for endobronchial palliation of NSCLC and its role in early stages of disease is being explored. We hypothesized that a novel photosensitizer, PS1, would be more effective than the standard agent, Porfimer sodium (Photofrin® or PFII), in treating human lung cancer xenografts in mice. Patient-derived NSCLC xenografts were established subcutaneously in SCID mice. Two groups of 5 mice were injected with PS1 [3-(1’-m-iodobenzyloxy)ethyl-3-devinylpyropheophorbide-a], a chlorophyll-a derivative or PFII (a purified version of hematoporphyrin derivative) then treated with non-thermal laser light. 4 mice were treated with laser light without photosensitizer and 6 mice received no treatment at all. All mice were then observed for tumor growth. The tumor growth endpoint, time-to-1000mm3, was evaluated using standard Kaplan-Meier methods and the log-rank test. Tumor H&E and Caspase3 staining was done to evaluate necrosis and apoptosis. The median time-to-1000mm3 was 12, 12, 26 and 52 days for the control, light only, PF II and PS1 groups. There was a significant association between the tumor-growth endpoint and treatment (p<0.05). H&E staining revealed <1%, 0%, 67% and 80% necrosis, and Caspase3 positivity was 2%, <1%, 17% and 39%, respectively in the same four groups. The mice treated with PS1 exhibited a longer time for tumor regrowth, showed more tumor necrosis and apoptosis compared to the other treatment groups. Thus, the novel photosensitizer, PS1, was demonstrated to be more effective than Porfimer sodium in this preclinical pilot study.
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