Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Cancer Prev Res (Phila). 2013 Apr;6(4):257-62. doi: 10.1158/1940-6207.CAPR-13-0055.
On the basis of substantial preclinical data showing the preventive efficacy of ginger and its constituents in vitro and in animal models, as well as a phase I pilot trial indicating that ginger extract is well tolerated in humans, Citronberg and colleagues conducted a pilot trial of ginger extract (2 g/day for 28 days) on biomarkers of cell proliferation [human telomerase reverse transcriptase (hTERT), MIB-1], differentiation (p21waf1/cip1), and apoptosis (Bax, Bcl-2) in colonic mucosa from individuals at high-risk for colorectal cancer. Results from the trial suggest that ginger may reduce proliferation in normal-appearing colorectal epithelium and increase apoptosis relative to proliferation, especially in the differentiation zone of colon crypts. The authors suggest that these results support a larger study to confirm the pilot data. Before proceeding with a larger trial, however, it seems prudent to confirm ginger as a chemopreventive for colorectal cancer in animals, particularly when tested in postinitiation protocols and to identify reliable molecular biomarkers of effect that could be evaluated in clinical trials. Pharmacokinetic studies to examine the distribution and localization of ginger compounds and metabolites in the differentiation and proliferative zones of colonic crypts in animals and humans would also be informative. Finally, because the effects of ginger on normal colonic mucosa seem minimal, consideration should be given to the conduct of future trials in humans with premalignant colorectal disease.
基于大量的临床前数据表明，姜及其成分在体外和动物模型中具有预防功效，以及一项 I 期试点试验表明，姜提取物在人体中耐受性良好，Citronberg 及其同事对姜提取物（每天 2 克，持续 28 天）进行了一项试点试验，研究其对高风险结直肠癌个体的结肠黏膜细胞增殖[人类端粒酶逆转录酶（hTERT）、MIB-1]、分化（p21waf1/cip1）和凋亡（Bax、Bcl-2）的生物标志物的影响。试验结果表明，姜可能会减少正常结肠上皮的增殖，并增加凋亡相对于增殖的比例，特别是在结肠隐窝的分化区。作者建议，这些结果支持进行更大规模的研究来证实试点数据。然而，在进行更大规模的试验之前，似乎明智的做法是在动物中确认姜作为结直肠癌的化学预防剂，特别是在启动后方案中进行测试，并确定可在临床试验中评估的可靠分子效应生物标志物。研究姜化合物和代谢物在动物和人体结肠隐窝分化和增殖区的分布和定位的药代动力学研究也将提供有价值的信息。最后，由于姜对正常结肠黏膜的影响似乎很小，因此应考虑在患有癌前结直肠疾病的人群中进行未来的试验。
