Flavone acetic acid (FAA) with recombinant interleukin-2 (TIL-2) in advanced malignant melanoma. II: Induction of nitric oxide production.
Flavone acetic acid (FAA) with recombinant interleukin-2 (TIL-2) in advanced malignant melanoma. II: Induction of nitric oxide production.
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DOI：
10.1038/bjc.1992.346
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发表时间：
1992-10
影响因子：
8.8
通讯作者：
O'Reilly, S M
中科院分区：
文献类型：
--
作者：
Thomsen, L L;Baguley, B C;Rustin, G J;O'Reilly, S M
从20名接受I期临床试验的患者中收集血浆样品，该I期临床试验用黄酮-8-乙酸（FAA; 4.8g m-2/剂量）与重组人白细胞介素-2（rhIL-2; 6-18 i.u. m-2/天）用于治疗转移性黑色素瘤。分析样品的硝酸盐含量，作为L-精氨酸氧化为一氧化氮的指示。治疗前血浆硝酸盐水平（53 +/- 4 μ M）显著高于健康志愿者（19 +/- 4 μ M）。治疗后获得的最大血浆硝酸盐浓度为190 +/- 29 μ M（范围为49至655 μ M），与FAA治疗的小鼠相当。大多数增加发生在开始输注rhIL-2 5天后的3-5天，但3个增加发生在单独输注FAA 1小时后的2天内。治疗后缓解的三名患者（两名完全缓解，一名部分缓解）的最大血浆硝酸盐浓度（368 +/- 143 μ M）显著高于疾病进展患者（P < 0.05）。低血压是主要的剂量限制性副作用，并且低血压的程度与血浆硝酸盐升高之间没有关系。结果提供证据表明，用FAA和rhIL-2治疗患者诱导一氧化氮的合成，一氧化氮是一种生理介质和潜在的细胞毒性剂。
Plasma samples were collected from 20 patients undergoing phase I clinical trial with flavone-8-acetic acid (FAA; 4.8 g m-2 per dose) in combination with recombinant human interleukin-2 (rhIL-2; 6-18 i.u. m-2 per day) for the treatment of metastatic melanoma. Samples were analysed for nitrate content as an indication of the oxidation of L-arginine to nitric oxide. Pretreatment plasma nitrate levels (53 +/- 4 microM) were significantly above those of healthy volunteers (19 +/- 4 microM). The maximum plasma nitrate concentration obtained after treatment, 190 +/- 29 microM (range 49 to 655 microM), was comparable to that of mice treated with FAA. Most of the increases occurred 3-5 days after initiation of a 5 day infusion of rhIL-2, but three of the increases occurred within 2 days of a 1 h infusion of FAA alone. The maximum plasma nitrate concentrations of the three patients which underwent remission (two complete, one partial) following treatment (368 +/- 143 microM) were significantly higher (P < 0.05) than those of patients with progressive disease. Hypotension was the major dose-limiting side effect, and there was no relationship between the degree of hypotension and the rise in plasma nitrate. The results provide evidence that treatment of patients with FAA and rhIL-2 induce the synthesis of nitric oxide, a physiological mediator and potential cytotoxic agent.