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一项评估黑树莓对巴雷特食管患者有益效果的I期初步研究。

A phase I pilot study evaluating the beneficial effects of black raspberries in patients with Barrett's esophagus.

作者信息

Kresty Laura A, Fromkes John J, Frankel Wendy L, Hammond Cynthia D, Seeram Navindra P, Baird Maureen, Stoner Gary D

机构信息

Division of Hematology & Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA.

出版信息

Oncotarget. 2016 Jul 7;9(82):35356-35372. doi: 10.18632/oncotarget.10457. eCollection 2018 Oct 19.

Abstract

Black raspberries inhibit a broad range of cancers in preclinical models which has led to clinical evaluations targeting premalignant lesions of the colon, oral cavity and esophagus. A phase I pilot study was conducted in twenty Barrett's esophagus (BE) patients to investigate the effect of lyophilized black raspberries (LBR) on urinary metabolites and markers of lipid peroxidation, DNA damage and tissue markers of cellular proliferation, detoxification, and inflammation. Surveys, biopsies, blood and urine samples were collected before and after 6 months of LBR treatment (32 or 45 g). LBR significantly reduced urinary excretion of 8-epi-prostaglandin F2α, a marker of lipid peroxidation linked to oxidative stress and free radical damage. Urinary levels of the ellagitannin metabolites, urolithin A-glucuronide, urolithin A-sulfate and dimethylellagic acid glucuronide were significantly increased following 12 and 26 weeks of LBR consumption and may prove useful as indicators of compliance in future clinical studies. Immunohistochemical staining of BE biopsies following LBR treatment showed significant increases in mean GST-pi levels, with 55.6% of subjects responding favorably. In summary, LBR significantly decreased urinary lipid peroxidation levels and significantly increased GST-pi, a marker of detoxification, in BE epithelium. Still, LBR may need to be formulated differently, administered at higher concentrations or multiple times a day to increase efficacy.

摘要

黑树莓在临床前模型中可抑制多种癌症,这促使针对结肠、口腔和食管癌前病变进行临床评估。对20例巴雷特食管(BE)患者进行了一项I期初步研究,以调查冻干黑树莓(LBR)对尿液代谢物以及脂质过氧化、DNA损伤和细胞增殖、解毒及炎症组织标志物的影响。在LBR治疗(32克或45克)6个月前后收集调查问卷、活检样本、血液和尿液样本。LBR显著降低了8-表前列腺素F2α的尿液排泄量,8-表前列腺素F2α是一种与氧化应激和自由基损伤相关的脂质过氧化标志物。食用LBR 12周和26周后,鞣花单宁代谢物尿石素A-葡萄糖醛酸苷、尿石素A-硫酸盐和二甲基鞣花酸葡萄糖醛酸苷的尿液水平显著升高,在未来临床研究中可能作为依从性指标。LBR治疗后BE活检的免疫组化染色显示平均GST-pi水平显著升高,55.6%的受试者反应良好。总之,LBR显著降低了BE上皮细胞的尿液脂质过氧化水平,并显著提高了解毒标志物GST-pi。尽管如此,可能需要对LBR进行不同的配方设计,以更高的浓度给药或一天多次给药,以提高疗效。

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