Randomized phase II trial of lyophilized strawberries in patients with dysplastic precancerous lesions of the esophagus.
Randomized phase II trial of lyophilized strawberries in patients with dysplastic precancerous lesions of the esophagus.
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冻干草莓的随机II期试验对食管发育不良癌性病变的患者。
DOI：
10.1158/1940-6207.capr-11-0469
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
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作者：
Chen T;Yan F;Qian J;Guo M;Zhang H;Tang X;Chen F;Stoner GD;Wang X
不典型增生是食管鳞状细胞癌（SCC）的组织学前兆。我们以前表明，饮食冷冻干燥，或冻干，草莓粉抑制N-亚硝基甲基苄胺诱导的大鼠食管SCC。在此观察的基础上，我们在中国进行了一项随机（非比较）II期试验，以研究两种剂量的冻干草莓对食管癌高危地区食管异型增生病变患者的影响。我们将75例经内镜检查确诊为食管癌前病变的患者随机分配，接受30 g/d（37例患者）或60 g/d（38例患者）的冻干草莓粉，持续6个月;将粉末与水混合并饮用。6个月后，我们以盲法评估这些病变的组织学分级变化（主要终点）。30 g/d的剂量对组织学或任何其他测量参数无显著影响。然而，60 g/d的剂量降低了36例接受组织学评价的患者中29例（80.6%）的发育异常癌前病变的组织学分级（P < 0.0001）。草莓粉耐受性良好，没有毒性作用或严重不良事件。草莓（60 g/d）还降低了诱导型一氧化氮合酶（iNOS）的蛋白表达水平79.5%（P < 0.001），环氧化酶-2（考克斯-2）降低62.9%磷酸化核因子κ B（NFκB）-p65（pNFκ B-p65）表达率降低62.6%（P < 0.001），磷酸化S6（pS 6）表达率降低73.2%（P < 0.001）。冻干草莓（60 g/d）也显著抑制Ki-67标记指数为37.9%（P = 0.023）。我们目前的研究结果表明，冻干草莓粉预防人类食管癌的潜力，支持这种天然药物在这种情况下的进一步临床试验。
Dysplasia is a histologic precursor of esophageal squamous cell carcinoma (SCC). We previously showed that dietary freeze-dried, or lyophilized, strawberry powder inhibits N-nitrosomethylbenzylamine-induced SCC in the rat esophagus. On the basis of this observation, we conducted a randomized (noncomparative) phase II trial in China to investigate the effects of two doses of freeze-dried strawberries in patients with esophageal dysplastic lesions in a high-risk area for esophageal cancer. We randomly assigned 75 patients identified by endoscopy to have dysplastic esophageal premalignant lesions to receive freeze-dried strawberry powder at either 30 g/d (37 patients) or 60 g/d (38 patients) for six months; the powder was mixed with water and drunk. After six months, we assessed the changes in histologic grade of these lesions (primary endpoint) in a blinded fashion. The dose of 30 g/d, did not significantly affect histology or any other measured parameter. The dose of 60 g/d, however, reduced the histologic grade of dysplastic premalignant lesions in 29 (80.6%) of the 36 patients at this dose who were evaluated for histology (P < 0.0001). The strawberry powder was well tolerated, with no toxic effects or serious adverse events. Strawberries (60 g/d) also reduced protein expression levels of inducible nitric oxide synthase (iNOS) by 79.5% (P < 0.001), cyclooxygenase-2 (COX-2) by 62.9% (P < 0.001), phospho-nuclear factor kappa B (NFκB)-p65 (pNFκB-p65) by 62.6% (P < 0.001), and phospho-S6 (pS6) by 73.2% (P < 0.001). Freeze-dried strawberries (60 g/d) also significantly inhibited the Ki-67 labeling index by 37.9% (P = 0.023). Our present results indicate the potential of freeze-dried strawberry powder for preventing human esophageal cancer, supporting further clinical testing of this natural agent in this setting.