Bonamin Leoni Villano, de Carvalho Aloisio Cunha, Waisse Silvia
Research Center, University Paulista, São Paulo 04026-002, Brazil.
Department of History of Science, Pontifical Catholic University of São Paulo, São Paulo 01303-000, Brazil.
Exp Ther Med. 2017 Jun;13(6):2723-2740. doi: 10.3892/etm.2017.4372. Epub 2017 Apr 21.
Mistletoe ( L.) has been used as complementary anticancer treatment for ~100 years. Although the clinical efficacy of mistletoe in cancer and associated survival benefits remain contested, several studies point to its effectiveness and others have reported antitumor and immunomodulatory properties. In the present review, a search was conducted for original articles reporting the outcomes of treatments for experimental animal tumors with mistletoe. The inclusion criteria were: Publication in English, from 1996 onwards and in peer-reviewed journals included in the database PubMed. The parameters analyzed were: Provenance and time of publication, rationale, methods (animal species used, mistletoe preparation, treatment protocol, tumor lineage, blinding, randomization, controls and concomitant treatments), outcomes and investigated mechanisms of action. A total of 37 studies met the inclusion criteria. The quality of the studies was adequate in the terms of sample size and use of controls, and the only animal species employed were mice and rats. However, few studies reported having performed random allocation and none reported blinding. There was wide variation in the type and preparation of mistletoe used, route of administration, regimen, tumor type and the mechanism of action assessed. A temporal trend was identified; earlier studies sought to establish the antitumor effect of mistletoe and its possible mechanisms, cytotoxicity and immunomodulation in particular, whereas the later ones tended to focus more on biologically active principles, genomics and oxidative stress. A total of 32/37 studies reported an antitumor effect, 3 of which had mixed results. A total of 2 studies did not detect any antitumor effect and a further 2 found stimulation of tumor growth in the treated groups. One study did not assess antitumor effects, investigating immunomodulation action instead. The quality of the studies was satisfactory and the majority reported positive outcomes. Nevertheless, there is a great deal of methodological heterogeneity among the studies, which precludes conclusive comparisons. Based on these results, the present authors strongly suggest developing guidelines for reporting mistletoe cancer treatment experiments.
槲寄生（Viscum album L.）作为辅助抗癌疗法已应用了约100年。尽管槲寄生在癌症治疗中的临床疗效及其对生存的益处仍存在争议，但多项研究表明其具有有效性，还有一些研究报告了其抗肿瘤和免疫调节特性。在本综述中，我们检索了报道用槲寄生治疗实验动物肿瘤结果的原始文章。纳入标准为：1996年起发表于英文且被数据库PubMed收录的同行评审期刊。分析的参数包括：出版来源和时间、理论依据、方法（所用动物物种、槲寄生制剂、治疗方案、肿瘤谱系、盲法、随机化、对照和伴随治疗）、结果以及所研究的作用机制。共有37项研究符合纳入标准。这些研究在样本量和对照使用方面质量尚可，所用动物物种仅为小鼠和大鼠。然而，很少有研究报告进行了随机分配，且无一报告采用了盲法。所使用的槲寄生类型和制剂、给药途径、方案、肿瘤类型以及所评估的作用机制存在很大差异。我们发现了一种时间趋势；早期研究试图确定槲寄生的抗肿瘤作用及其可能机制，尤其是细胞毒性和免疫调节，而后期研究则更倾向于关注生物活性成分、基因组学和氧化应激。37项研究中有32项报告了抗肿瘤作用，其中3项结果不一。共有2项研究未检测到任何抗肿瘤作用，另有2项发现治疗组肿瘤生长受到刺激。1项研究未评估抗肿瘤作用，而是研究了免疫调节作用。这些研究的质量令人满意，大多数报告了阳性结果。然而，研究之间存在大量方法学异质性，这妨碍了进行确定性比较。基于这些结果，本文作者强烈建议制定槲寄生癌症治疗实验报告指南。
