Research

Blackberries and Colon Cancer Prevention

Clin Cancer Res. 2011 Feb 1;17(3):598-610. doi: 10.1158/1078-0432.CCR-10-1260. Epub 2010 Dec 1.

Modulation of genetic and epigenetic biomarkers of colorectal cancer in humans by black raspberries: a phase I pilot study.

Wang LS, Arnold M, Huang YW, Sardo C, Seguin C, Martin E, Huang TH, Riedl K, Schwartz S, Frankel W, Pearl D, Xu Y, Winston J 3rd, Yang GY, Stoner G.

Source
Department of Internal Medicine, Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, Ohio 43240, USA. This email address is being protected from spambots. You need JavaScript enabled to view it.

PURPOSE:
This study evaluated the effects of black raspberries (BRBs) on biomarkers of tumor development in the human colon and rectum including methylation of relevant tumor suppressor genes, cell proliferation, apoptosis (cell death), angiogenesis (new blood supply), and expression of Wnt pathway genes.

EXPERIMENTAL DESIGN:
Biopsies of adjacent normal tissues and colorectal adenocarcinomas were taken from 20 patients before and after oral consumption of BRB powder (60 g/d) for 1-9 weeks. Methylation status of promoter regions of five tumor suppressor genes was quantified. Protein expression of DNA methyltransferase 1 (DNMT1) and genes associated with cell proliferation, apoptosis, angiogenesis, and Wnt signaling were measured.

RESULTS:
The methylation of three Wnt inhibitors, SFRP2, SFRP5, and WIF1, upstream genes in Wnt pathway, and PAX6a, a developmental regulator, was modulated in a protective direction by BRBs in normal tissues and in colorectal tumors only in patients who received BRB treatment for an average of 4 weeks, but not in all 20 patients with 1-9 weeks of BRB treatment. This was associated with decreased expression of DNMT1. BRBs modulated expression of genes associated with Wnt pathway, proliferation, apoptosis, and angiogenesis in a protective direction.

CONCLUSIONS:
These data provide evidence of the ability of BRBs to demethylate tumor suppressor genes and to modulate other biomarkers of tumor development in the human colon and rectum. While demethylation of genes did not occur in colorectal tissues from all treated patients, the positive results with the secondary endpoints suggest that additional studies of BRBs for the prevention of colorectal cancer in humans now appear warranted.
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Probiotics for diarrhea from radiation therapy

(Clin Nutr. 2013 Oct 24. pii: S0261-5614(13)00274-4. doi: 10.1016/j.clnu.2013.10.015.)

A randomized double-blind controlled trial: Impact of probiotics on diarrhea in patients treated with pelvic radiation.

Demers M, Dagnault A, Desjardins J.

Department of Radio-Oncology, University Health Center, Hôtel Dieu de Québec, Québec, Canada; Department of Clinical Nutrition, University Health Center, Hôtel Dieu de Québec, Québec, Canada. Electronic address: This email address is being protected from spambots. You need JavaScript enabled to view it..

BACKGROUND & AIMS:
Radical radiation therapy is commonly used for treatment of pelvic cancer. Up to 80% of patients receiving radiotherapy will develop acute radiation induced diarrhea. The primary aim of this randomized double blind controlled trial is to evaluate the effect of the probiotic Bifilact® on moderate and severe treatment-induced diarrhea during pelvic radiation.

METHODS:
Patients with pelvic cancers were treated between 2006 and 2010 at L'Hôtel-Dieu de Québec, University Health Center. Some patients had surgery before pelvic radiotherapy and some received chemotherapy. A total of 246 Patients were randomized between a placebo and either of two regiments of double strain Bifilact® probiotics (Lactobacillus acidophilus LAC-361 and Bifidobacterium longum BB-536): a standard dose twice a day (1.3 billion CFU) or a high dose three times a day (10 billion CFU). Patients were trained to record their digestive symptoms daily with a standardized scale and they met a registered dietician and radiation oncologist every week during treatment. The main analysis compared time to first appearance of grade ≥2-3-4 diarrhea using Kaplan-Meier curves as measured by proportion of patients without moderate and severe diarrhea.

RESULTS:
229 patients were analyzed. The difference between the groups for overall grade 2-3-4 diarrhea was not statistically significant (p = 0.13). However at 60 days, the proportion of patients without moderate and severe diarrhea in the standard dose group (35%) was more than twice as high as that of the placebo group (17%) with a hazard ratio of 0.69 (p = 0.04). In patients who had surgery, the standard probiotics dose group had a better proportion of patients without very severe diarrhea than the placebo group, respectively 97% and 74% (p = 0.03). In all groups, the average number of bowel movements per day during treatment was less than 3 soft stools (p = 0.80) and the median abdominal pain less than 1 based on the National Cancer Institute scale (p = 0.23).

CONCLUSION:
Standard dose of Bifilact® may reduce radiation induced grade 2-3-4 diarrhea at the end of the treatment of patients with pelvic cancer. In patients operated on before RT, a standard dose of probiotics may reduce radiation induced grade 4 diarrhea. Nutritional interventions by a registered dietician seemed to reduce global digestive symptoms.

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