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.

A Phase Ib Study of the Effects of Black Raspberries on Rectal Polyps in Patients with Familial Adenomatous Polyposis

“…1, Supplementary Table S5). In other clinical trials with oral administration of berries, BRBs have been shown to be well tolerated and exert protective effects in patients with colorectal cancer (14) and Barrett's esophagus (15), and strawberries regress mild dysplastic esophageal lesions that are precursors to squamous cell carcinoma (25). Accordingly, we anticipated that oral BRBs plus BRB suppositories could be more effective than suppositories alone in regressing polyps in patients with FAP.…”

Dietary Consumption of Black Raspberries or Their Anthocyanin Constituents Alters Innate Immune Cell Trafficking in Esophageal Cancer

“…Preneoplastic changes, as well as changes in the expression of inflammatory and angiogenic biomarkers, closely resemble changes observed in human esophageal SCC. Lesions follow the progression sequence from normal>hyperplasia>mild, moderate, and severe dysplasia>papilloma>to esophageal SCC (4,29). Dysregulated changes in inflammatory biomarker expression, namely COX-2, iNOS, and NF-kB, have been reported during tumor development in this model (6,7,9,29,30).…”

“…Lesions follow the progression sequence from normal>hyperplasia>mild, moderate, and severe dysplasia>papilloma>to esophageal SCC (4,29). Dysregulated changes in inflammatory biomarker expression, namely COX-2, iNOS, and NF-kB, have been reported during tumor development in this model (6,7,9,29,30). The present study evaluates whether BRBs, their component ACs, and PCA alter immune cell trafficking within the esophagi of NMBA-treated F-344 rats, and whether these changes are associated with inhibition of tumorigenesis.…”

Esophageal Cancer: Priorities for Prevention

“…To test these hypotheses, two large chemoprevention trials were implemented-one in the general population [65] and the other in patients with high-risk precursor lesions [66]-to test a range of nutritional interventions, but they delivered essentially null results [67, 68••]. When these findings were placed alongside null findings from other trials [69,70], enthusiasm for further nutritional interventions for ESCC was tempered. More recently, a small number of cohort studies conducted in both Western and Chinese populations have reported that diets with high intakes of fruits or vegetables, or with indices of high dietary quality, are associated with reduced risks of ESCC [47][48][49]71].…”