Prevention of second primary tumors by an acyclic retinoid in patients with hepatocellular carcinoma - Updated analysis of the long-term follow-up data
Prevention of second primary tumors by an acyclic retinoid in patients with hepatocellular carcinoma - Updated analysis of the long-term follow-up data
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DOI：
10.1159/000082093
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发表时间：
2005-01-01
期刊：
影响因子：
4.6
通讯作者：
Moriwaki, H
中科院分区：
文献类型：
--
作者：
Takai, K;Okuno, M;Moriwaki, H
口服非环类维甲酸(一种合成维生素A类似物)，为期12个月(48周)，可防止第二原发肝细胞癌(HCC)的发展，并提高接受最初肿瘤根治治疗的患者的存活率。在1996年和1999年报道的随机对照研究之后，我们继续通过医学影像和血液化学分析对患者进行随访，发现无环维A酸类药物的预防效果在随机化后199周(或维甲酸类药物用药结束后151周)持续。维甲酸的作用不是通过减轻肝脏坏死性炎症来实现的，因为维甲酸组的血清转氨酶活性没有明显下降。这种观察似乎与干扰素的防癌机制截然不同，干扰素是一种有效的肝细胞癌免疫预防药物。我们还发现维生素K缺乏或拮抗剂-II诱导的血清凝集素反应性甲胎蛋白(AFP-L3)和蛋白(PIVKA-II)水平下降，两者都表明存在潜伏的肝细胞癌细胞。这些结果表明，去环维A酸可以在这些恶性克隆扩展到临床可检测到的肿瘤之前将其删除，从而抑制第二原发癌。一旦这种潜在克隆被根除，很可能至少需要几年时间才能在临床上出现下一个癌症克隆。这可能解释了维甲酸即使在有限的服药时间后仍有长期疗效的原因。版权所有(C)2005 S.Karger AG，巴塞尔。
Oral administration with acyclic retinoid, a synthetic vitamin A analog, for a limited period of 12 months (48 weeks) prevented the development of second primary hepatocellular carcinoma (HCC) and also improved the survival of patients who underwent curative treatments of the initial tumor. Following that randomized controlled study reported in 1996 and 1999, we have continued to follow up the patients by medical imaging and blood chemical analyses, and found that the preventive effect of acyclic retinoid lasted up to 199 weeks after randomization (or 151 weeks after completion of retinoid administration). The retinoid's effect was not mediated by reduction in hepatic necro-inflammation since no significant decrease in serum aminotransferase activity was seen in the retinoid group. Such observation seems quite distinct from the cancer-preventive mechanism of interferon, a potent immunopreventive agent for HCC. We have also shown here the reduction by the retinoid in serum levels of lectin-reactive alpha-fetoprotein (AFP-L3) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), both of which indicate the presence of latent HCC cells. These results suggest that acyclic retinoid may delete such malignant clones before they expand to clinically detectable tumors and thereby inhibited second primary HCC. Once such latent clones are eradicated, it may well take at least several years for the next cancer clone to arise clinically. This may possibly explain a reason for the long-term effect of the retinoid even after the limited period of administration. Copyright (C) 2005 S. Karger AG, Basel.