Winther J B
Department of Ophthalmology, Holstebro Centralsygehus, Denmark.
Acta Ophthalmol Suppl (1985). 1990(197):1-37.
A retinoblastoma-like tumour has been established and characterized in terms of growth rates in vitro and in vivo, and by histopathology and chromosome analysis. Injected tumour cells grew regularly in the vitreous body with a blood supply from the retinal vessels. The tumour tissue was histopathologically similar to that of anaplastic human retinoblastomas. Almost all the cells had a triploid chromosome number and the DNA amount in tumours was stable, suggesting a stable tumour system without drift against more anaplastic degrees. Tumour cells plated in culture flasks were grown in colonies. Evaluation of the number of clonogenic cells in treated, relative to non-treated flasks reflected a quantitative treatment response. When the cells were injected into the eyes of young rats, solid tumors were formed which grew regularly until perforation of the globes. The tumours were suitable for assessment of therapeutic response in terms of local tumour control after treatment. Photodynamic therapy (PDT) of cancers, using hematoporphyrin derivatives (HPD) and visible light, is a therapeutic modality where HPD is administered 1-5 days before local light irradiation of the tumour. The combination of HPD, light energy and oxygen produces the cytotoxic agent singlet oxygen which only exists in its active state for a few milliseconds. Using this modality, it may be possible to obtain local tumour destruction in light-irradiated areas and avoid spreading of the cytotoxic agents to other organs. The effect of PDT with purified HPD (Photofrin II) and red light has been evaluated in the characterized retinoblastoma-like tumour in vivo and in vitro. The experiments demonstrated that Photofrin II and red light destroys cells in tissue culture flasks. Local control of intraocular retinoblastoma-like tumours was obtained in up to 33% of the animals following a single treatment. Adverse effects in the present model were corneal and conjunctival damage. Generally, the effect of PDT increased with larger Photofrin II doses, higher energy doses or a shorter time interval between drug administration and light irradiation. Damage to the cornea or conjunctiva limited the maximum tolerable treatment doses in the present model. The experiments suggests that PDT is a safer treatment with Photofrin II 2.5 mg/kg and a high light energy dose than with 10 mg/kg and an equivalent lower light energy dose. In tissue culture flasks, the cell inactivation did not depend on the light energy rate but only on the total delivered energy dose. The cells had a low capacity to repair sublethal damage.(ABSTRACT TRUNCATED AT 400 WORDS)
已建立一种视网膜母细胞瘤样肿瘤，并对其体外和体内生长速率、组织病理学及染色体分析进行了表征。注射的肿瘤细胞在玻璃体中借助视网膜血管供血而正常生长。肿瘤组织在组织病理学上与间变性人视网膜母细胞瘤相似。几乎所有细胞都有三倍体染色体数，肿瘤中的DNA量稳定，这表明该肿瘤系统稳定，不会向更高间变程度漂移。接种于培养瓶中的肿瘤细胞形成集落生长。相对于未处理的培养瓶，评估处理后培养瓶中克隆形成细胞的数量反映了定量的治疗反应。当将这些细胞注入幼鼠眼中时，会形成实体瘤，肿瘤会正常生长直至眼球穿孔。这些肿瘤适合用于评估治疗后局部肿瘤控制方面的治疗反应。使用血卟啉衍生物（HPD）和可见光的癌症光动力疗法（PDT）是一种治疗方式，即在局部肿瘤光照射前1 - 5天给予HPD。HPD、光能和氧气的组合产生细胞毒性剂单线态氧，其仅在活性状态下存在几毫秒。使用这种方式，有可能在光照射区域实现局部肿瘤破坏，并避免细胞毒性剂扩散到其他器官。已在体内和体外对纯化的HPD（光卟啉II）和红光进行的PDT对表征的视网膜母细胞瘤样肿瘤的作用进行了评估。实验表明，光卟啉II和红光可破坏组织培养瓶中的细胞。单次治疗后，高达33%的动物实现了眼内视网膜母细胞瘤样肿瘤的局部控制。本模型中的不良反应为角膜和结膜损伤。一般来说，PDT的效果随着光卟啉II剂量增加、能量剂量增加或给药与光照射之间的时间间隔缩短而增强。在本模型中，角膜或结膜损伤限制了最大可耐受治疗剂量。实验表明，与10 mg/kg及等效较低光能剂量相比，使用2.5 mg/kg光卟啉II和高光能剂量进行PDT是一种更安全的治疗方法。在组织培养瓶中，细胞失活不取决于光能速率，而仅取决于总传递能量剂量。细胞修复亚致死损伤的能力较低。
