The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study

<p>Abstract</p> <p>Background</p> <p>Several GI peptides linked to intestinal barrier function could be involved in the modification of intestinal permeability and the onset of diarrhea during adjuvant chemotherapy. The aim of the study was to evaluate the circulating l...

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Main Authors: Russo Francesco, Linsalata Michele, Clemente Caterina, D’Attoma Benedetta, Orlando Antonella, Campanella Giovanna, Giotta Francesco, Riezzo Giuseppe
Format: Article
Language:English
Published: BMC 2013-02-01
Series:BMC Cancer
Subjects:
Online Access:http://www.biomedcentral.com/1471-2407/13/56
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author Russo Francesco
Linsalata Michele
Clemente Caterina
D’Attoma Benedetta
Orlando Antonella
Campanella Giovanna
Giotta Francesco
Riezzo Giuseppe
author_facet Russo Francesco
Linsalata Michele
Clemente Caterina
D’Attoma Benedetta
Orlando Antonella
Campanella Giovanna
Giotta Francesco
Riezzo Giuseppe
author_sort Russo Francesco
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Several GI peptides linked to intestinal barrier function could be involved in the modification of intestinal permeability and the onset of diarrhea during adjuvant chemotherapy. The aim of the study was to evaluate the circulating levels of zonulin, glucagon-like peptide-2 (GLP-2), epidermal growth factor (EGF) and ghrelin and their relationship with intestinal permeability and chemotherapy induced diarrhea (CTD).</p> <p>Methods</p> <p>Sixty breast cancer patients undergoing an FEC60 regimen were enrolled, 37 patients completed the study. CTD(+) patients were discriminated by appropriate questionnaire and criteria. During chemotherapy, intestinal permeability was assessed by lactulose/mannitol urinary test on day 0 and day 14. Zonulin, GLP-2, EGF and ghrelin circulating levels were evaluated by ELISA tests at five time-points (days 0, 3, 10, 14, and 21).</p> <p>Results</p> <p>During FEC60 administration, the lactulose/mannitol ratio was significantly higher on day 14 than at baseline. Zonulin levels were not affected by chemotherapy, whereas GLP-2 and EGF levels decreased significantly. GLP-2 levels on day 14 were significantly lower than those on day 0 and day 3, while EGF values were significantly lower on day 10 than at the baseline. In contrast, the total concentrations of ghrelin increased significantly at day 3 compared to days 0 and 21, respectively. Ten patients (27%) suffered from diarrhea. On day 14 of chemotherapy, a significant increase of the La/Ma ratio occurred in CTD(+) patients compared to CTD(−) patients. With regards to circulating gut peptides, the AUCg of GLP-2 and ghrelin were significantly lower and higher in CTD(+) patients than CTD(−) ones, respectively. Finally in CTD(+) patients a significant and inverse correlation between GLP-2 and La/Ma ratio was found on day 14.</p> <p>Conclusions</p> <p>Breast cancer patients undergoing FEC60 showed alterations in the intestinal permeability, which was associated with modifications in the levels of GLP-2, ghrelin and EGF. In CTD(+) patients, a different GI peptide profile and increased intestinal permeability was found in comparison to CTD(−) patients. This evidence deserves further studies for investigating the potentially different intestinal luminal and microbiota conditions.</p> <p>Trial registration</p> <p>Clinical trial NCT01382667</p>
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spelling doaj.art-d2174e262b8a4499882b6ef428a794a22022-12-22T03:29:25ZengBMCBMC Cancer1471-24072013-02-011315610.1186/1471-2407-13-56The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational studyRusso FrancescoLinsalata MicheleClemente CaterinaD’Attoma BenedettaOrlando AntonellaCampanella GiovannaGiotta FrancescoRiezzo Giuseppe<p>Abstract</p> <p>Background</p> <p>Several GI peptides linked to intestinal barrier function could be involved in the modification of intestinal permeability and the onset of diarrhea during adjuvant chemotherapy. The aim of the study was to evaluate the circulating levels of zonulin, glucagon-like peptide-2 (GLP-2), epidermal growth factor (EGF) and ghrelin and their relationship with intestinal permeability and chemotherapy induced diarrhea (CTD).</p> <p>Methods</p> <p>Sixty breast cancer patients undergoing an FEC60 regimen were enrolled, 37 patients completed the study. CTD(+) patients were discriminated by appropriate questionnaire and criteria. During chemotherapy, intestinal permeability was assessed by lactulose/mannitol urinary test on day 0 and day 14. Zonulin, GLP-2, EGF and ghrelin circulating levels were evaluated by ELISA tests at five time-points (days 0, 3, 10, 14, and 21).</p> <p>Results</p> <p>During FEC60 administration, the lactulose/mannitol ratio was significantly higher on day 14 than at baseline. Zonulin levels were not affected by chemotherapy, whereas GLP-2 and EGF levels decreased significantly. GLP-2 levels on day 14 were significantly lower than those on day 0 and day 3, while EGF values were significantly lower on day 10 than at the baseline. In contrast, the total concentrations of ghrelin increased significantly at day 3 compared to days 0 and 21, respectively. Ten patients (27%) suffered from diarrhea. On day 14 of chemotherapy, a significant increase of the La/Ma ratio occurred in CTD(+) patients compared to CTD(−) patients. With regards to circulating gut peptides, the AUCg of GLP-2 and ghrelin were significantly lower and higher in CTD(+) patients than CTD(−) ones, respectively. Finally in CTD(+) patients a significant and inverse correlation between GLP-2 and La/Ma ratio was found on day 14.</p> <p>Conclusions</p> <p>Breast cancer patients undergoing FEC60 showed alterations in the intestinal permeability, which was associated with modifications in the levels of GLP-2, ghrelin and EGF. In CTD(+) patients, a different GI peptide profile and increased intestinal permeability was found in comparison to CTD(−) patients. This evidence deserves further studies for investigating the potentially different intestinal luminal and microbiota conditions.</p> <p>Trial registration</p> <p>Clinical trial NCT01382667</p>http://www.biomedcentral.com/1471-2407/13/56Breast cancerChemotherapy-induced diarrheaEpidermal growth factorIntestinal permeabilityGhrelinGlucagon-like peptide 2Gut peptidesZonulin
spellingShingle Russo Francesco
Linsalata Michele
Clemente Caterina
D’Attoma Benedetta
Orlando Antonella
Campanella Giovanna
Giotta Francesco
Riezzo Giuseppe
The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study
BMC Cancer
Breast cancer
Chemotherapy-induced diarrhea
Epidermal growth factor
Intestinal permeability
Ghrelin
Glucagon-like peptide 2
Gut peptides
Zonulin
title The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study
title_full The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study
title_fullStr The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study
title_full_unstemmed The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study
title_short The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study
title_sort effects of fluorouracil epirubicin and cyclophosphamide fec60 on the intestinal barrier function and gut peptides in breast cancer patients an observational study
topic Breast cancer
Chemotherapy-induced diarrhea
Epidermal growth factor
Intestinal permeability
Ghrelin
Glucagon-like peptide 2
Gut peptides
Zonulin
url http://www.biomedcentral.com/1471-2407/13/56
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