Potentiation of photodynamic therapy antitumor activity in mice by nitric oxide synthase inhibition is fluence rate dependent

Potentiation of photodynamic therapy antitumor activity in mice by nitric oxide synthase inhibition is fluence rate dependent
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DOI:
10.1111/j.1751-1097.1999.tb01950.x
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发表时间:
1999-07-01
影响因子:
3.3
通讯作者:
Vaughan, LA
Vaughan, LA
中科院分区:
生物学3区
文献类型:
--
作者:
Henderson, BW;Sitnik-Busch, TM;Vaughan, LA

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研究了全身应用一氧化氮合酶(NOS)抑制剂N-G-硝基-L-精氨酸(L-NNA)联合光动力疗法(PDT)对皮下放射诱导纤维肉瘤小鼠肿瘤反应、肿瘤氧合、肿瘤和正常皮肤灌注的影响。使用光敏剂Photofrin(R)(5 mg/kg)结合低通量率(30 mW/cm(2))和高通量率(150 mW/cm(2))方案进行光动力学治疗,总通量为100 J/cm(2)。低通量率PDT产生了类似于15%的肿瘤治愈,在PDT之前或之后5分钟施用20 mg/kg L-NNA没有显著改变该反应。相反,高通量率PDT本身不产生肿瘤治愈,但是在PDT之前或之后添加L-NNA分别产生了类似于30%和类似于10%的肿瘤治愈。L-NNA本身倾向于降低肿瘤pO(2)水平和灌注,但仅在一个时间点(1 h)测量的一个氧合参数(%值)达到统计学显著差异
The effects of systemic administration of the nitric oxide synthase (NOS) inhibitor N-G-nitro-L-arginine (L-NNA) in combination with photodynamic therapy (PDT) on tumor response, tumor oxygenation and tumor and normal skin perfusion were studied in C3H mice bearing subcutaneous radiation-induced firbrosarcoma turners. Photodynamic therapy was carried out using the photosensitizer Photofrin(R) (5 mg/kg) in conjunction with a low fluence rate (30 mW/cm(2)) and a high fluence rate (150 mW/cm(2)) protocol at a total fluence of 100 J/cm(2). Low fluence rate PDT produced similar to 15% tumor cures, a response not significantly altered by administration of 20 mg/kg L-NNA either 5 min before or after PDT, In contrast, high fluence rate PDT produced no tumor cures by itself, but addition of L-NNA either pre- or post-PDT resulted in similar to 30% and similar to 10% tumor dares, respectively, The L-NNA by itself tended to decrease tumor pO(2) levels and perfusion, but statistically significant differences were reached only at one time point (1 h) with one of the oxygenation parameters measured (% values