Gustafsson Lotta, Leijonhufvud Irene, Aronsson Annika, Mossberg Ann-Kristin, Svanborg Catharina
Institute of Laboratory Medicine, Department of Microbiology, Immunology, and Glycobiology, University of Lund, Lund, Sweden.
N Engl J Med. 2004 Jun 24;350(26):2663-72. doi: 10.1056/NEJMoa032454.
We studied the effect on skin papillomas of topical application of a complex of alpha-lactalbumin and oleic acid (often referred to as human alpha-lactalbumin made lethal to tumor cells [HAMLET]) to establish proof of the principle that alpha-lactalbumin-oleic acid kills transformed cells but not healthy, differentiated cells.
Forty patients with cutaneous papillomas that were resistant to conventional treatment were enrolled in a randomized, placebo-controlled, double-blind study, in which alpha-lactalbumin-oleic acid or saline placebo was applied daily for three weeks and the change in the volume of each lesion was recorded. After this first phase of the study, 34 patients participated in the second phase, an open-label trial of a three-week course of alpha-lactalbumin-oleic acid. Approximately two years after the end of the open-label phase of the study, 38 of the original 40 patients were examined, and long-term follow-up data were obtained.
In the first phase of the study, the lesion volume was reduced by 75 percent or more in all 20 patients in the alpha-lactalbumin-oleic acid group, and in 88 of 92 papillomas; in the placebo group, a similar effect was evident in only 3 of 20 patients (15 of 74 papillomas) (P<0.001). After the patients in the initial placebo group had been treated with alpha-lactalbumin-oleic acid in the second phase of the study, a median reduction of 82 percent in lesion volume was observed. At follow-up two years after the end of the second phase, all lesions had completely resolved in 83 percent of the patients treated with alpha-lactalbumin-oleic acid, and the time to resolution was shorter in the group originally assigned to receive alpha-lactalbumin-oleic acid than among patients originally in the placebo group (2.4 vs. 9.9 months; P<0.01). No adverse reactions were reported, and there was no difference in the outcomes of treatment between immunocompetent and immunosuppressed patients.
Treatment with topical alpha-lactalbumin-oleic acid has a beneficial and lasting effect on skin papillomas.
我们研究了局部应用α-乳白蛋白与油酸的复合物（通常称为对肿瘤细胞有致死性的人α-乳白蛋白[HAMLET]）对皮肤乳头状瘤的影响，以证实α-乳白蛋白 - 油酸可杀死转化细胞而非健康的分化细胞这一原理。
40例对传统治疗有抵抗性的皮肤乳头状瘤患者被纳入一项随机、安慰剂对照、双盲研究，其中每天应用α-乳白蛋白 - 油酸或生理盐水安慰剂，为期三周，并记录每个病变体积的变化。在研究的第一阶段结束后，34例患者参与了第二阶段，即α-乳白蛋白 - 油酸为期三周疗程的开放标签试验。在研究的开放标签阶段结束约两年后，对最初40例患者中的38例进行了检查，并获得了长期随访数据。
在研究的第一阶段，α-乳白蛋白 - 油酸组的所有20例患者以及92个乳头状瘤中的88个，病变体积减少了75%或更多；在安慰剂组中，20例患者中只有3例（74个乳头状瘤中的15个）出现了类似效果（P<0.001）。在研究的第二阶段，最初安慰剂组的患者接受α-乳白蛋白 - 油酸治疗后，观察到病变体积中位数减少了82%。在第二阶段结束两年后的随访中，接受α-乳白蛋白 - 油酸治疗的患者中，83%的患者所有病变完全消退，且最初分配接受α-乳白蛋白 - 油酸治疗的组病变消退时间比最初在安慰剂组的患者短（2.4个月对9.9个月；P<0.01）。未报告不良反应，免疫功能正常和免疫抑制患者的治疗结果无差异。
局部应用α-乳白蛋白 - 油酸治疗对皮肤乳头状瘤有有益且持久的效果。
