title: Randomized phase II trial of lyophilized strawberries in patients with dysplastic precancerous lesions of the esophagus.
abstract: 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.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, 410 West 12 Avenue, Columbus, OH 43210, USA. tong.chen@osumc.edu
authors.forename: Tong
authors.initials: T
authors.lastname: Chen
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
authors.forename: Jiaming
authors.initials: J
authors.lastname: Qian
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Guo
authors.forename: Hongbing
authors.initials: H
authors.lastname: Zhang
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Tang
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.forename: Gary D
authors.initials: GD
authors.lastname: Stoner
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000517:prevention & control* / Q000628:therapy; D049109:Cell Proliferation; D002681:China; D004724:Endoscopy / Q000379:methods; D004938:Esophageal Neoplasms / Q000517:prevention & control* / Q000628:therapy; D005260:Female; D031985:Fragaria / Q000378:metabolism*; D005612:Freeze Drying; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010936:Plant Extracts / Q000627:therapeutic use*; D011208:Powders; D011230:Precancerous Conditions
chemical_list: D010936:Plant Extracts; D011208:Powders