Influence of surgically induced gastric and gastroduodenal content reflux on esophageal carcinogenesis – experimental model in Wistar female rats *

Ll., M. C.; Cd, Kruel; Lm, Kliemann; Cavazzola, Leandro Totti; L, Boeno Rda; Pc, Silber; Rs, Grossi

doi:10.1046/j.1442-2050.1999.00011.x

Cited by 21 publications

(9 citation statements)

References 33 publications

(52 reference statements)

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“…Tobacco and chronic alcohol have long been considered carcinogenic risk factors of laryngopharyngeal and hypopharyngeal cancer 2, 3. Gastroduodenal reflux disease (GDRD), a variant of gastro‐oesophageal reflux disease (GERD), has also recently been considered a risk factor that may exert independent carcinogenic potential related to chronic effects of toxic gastroduodenal fluid (GDF) on hypopharyngeal epithelial cells 4, 5, 6, 7…”

Section: Introductionmentioning

confidence: 99%

NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in human hypopharyngeal cells

Doukas¹,

Vageli²,

Sasaki³

2018

J Cellular Molecular Medi

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We previously demonstrated that acidic bile activates NF‐κB, deregulating the expression of oncogenic miRNA markers, in pre‐malignant murine laryngopharyngeal mucosa. Here, we hypothesize that the in vitro exposure of human hypopharyngeal cells to acidic bile deregulates cancer‐related miRNA markers that can be reversed by BAY 11‐7082, a pharmacologic NF‐κB inhibitor. We repetitively exposed normal human hypopharyngeal primary cells and human hypopharyngeal keratinocytes to bile fluid (400 μmol/L), at pH 4.0 and 7.0, with/without BAY 11‐7082 (20 μmol/L). We centred our study on the transcriptional activation of oncogenic miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375, miR‐451a and NF‐κB‐related genes, previously linked to acidic bile‐induced pre‐neoplastic events. Our novel findings in vitro are consistent with our hypothesis demonstrating that BAY 11‐7082 significantly reverses the acidic bile‐induced oncogenic miRNA phenotype, in normal hypopharyngeal cells. BAY 11‐7082 strongly inhibits the acidic bile‐induced up‐regulation of miR‐192 and down‐regulation of miR‐451a and significantly decreases the miR‐21/375 ratios, previously related to poor prognosis in hypopharyngeal cancer. This is the first in vitro report that NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in normal human hypopharyngeal cells, suggesting that acidic bile‐induced events are directly or indirectly dependent on NF‐κB signalling.

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Section: Introductionmentioning

confidence: 99%

NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in human hypopharyngeal cells

Doukas¹,

Vageli²,

Sasaki³

2018

J Cellular Molecular Medi

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“…Experimental studies have been designed to evaluate the true role of duodenal reflux using surgical models to induce alkaline reflux in rats 12–15. The results of these studies have a potential role in directly influencing the future of DGER treatment.…”

Section: Introductionmentioning

confidence: 99%

Radiological evaluation of the patency of duodenal-esophageal anastomosis during a long postoperative follow-up: effectiveness of an alkaline reflux model in rats

Bigolin¹,

Grossi²,

Montes³

et al. 2011

CEG

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Background:Performing experimental studies has played an important role in acquiring knowledge about esophageal carcinogenesis. In this context, the choice of a more reliable experimental model requires proof of its effectiveness in order to lend greater credibility to the results. The objective of this study was to evaluate the patency of duodenal-esophageal anastomosis during long-term postoperative follow-up in rats.Methods:This was an experimental study in which 45 female Wistar rats were used. A side-to-side anastomosis was performed, going from the anterior side of the esophagus to the second duodenal portion. A standardized radiological technique was used to carry out a contrasted radiological study of the esophagus, stomach, and duodenum during weeks 4, 12, 20, and 30 after surgery. Different contrast media were used, and the animals were divided into groups, ie, group 1 (100% barium sulfate), group 2 (50% barium sulfate), and group 3 (60% aqueous iodinated contrast media). Contrast radiographs were taken in each group at weeks 4, 12, 20, and 30 after the surgical procedure. The radiographic images were evaluated by two radiologists who were blinded regarding the contrast groups. Macroscopic evaluation of each animal was compared with the radiological findings.Results:Postoperative mortality was 13.33%. The remaining animals were divided into study groups. All the contrast radiological examinations showed evidence of the location of the esophagus, stomach, and proximal portion of the intestine, and demonstrated the laterolateral relationship of the distal esophagus and the duodenum in the epigastric region. Patency of the anastomosis was observed at each examination period. The different contrast media used were able to demonstrate this outcome shortly after the first phase of injection. Necropsies corroborated the radiological findings.Conclusion:Regardless of the contrast agent used, contrasted radiography revealed that side-to-side duodenal-esophageal anastomosis in rats allowed patent communication during long-term postoperative follow-up.

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“…Histology of these neoplasms was well-differentiated adenocarcinoma (Figure 9). Such esophageal carcinogenesis caused by surgical procedures can be potentiated by a carcinogen NMNA, a semipurified high-fat diet, diethylnitrosamine (DEN) [93], or iron overnutrition [92]. Thus, It appears that gastroduodenoesophageal reflux (GDER) is significantly more deleterious to esophageal mucosa than GER, and GDER in isolation is an esophageal carcinogen, causing BE and esophageal adenocarcinoma [93].…”

Section: Animal Models Of Esophageal Adenocarcinomamentioning

confidence: 99%

“…Such esophageal carcinogenesis caused by surgical procedures can be potentiated by a carcinogen NMNA, a semipurified high-fat diet, diethylnitrosamine (DEN) [93], or iron overnutrition [92]. Thus, It appears that gastroduodenoesophageal reflux (GDER) is significantly more deleterious to esophageal mucosa than GER, and GDER in isolation is an esophageal carcinogen, causing BE and esophageal adenocarcinoma [93]. This Barrett's epithelium is similar to human BE with specialized types of goblet cells (containing sialomucin or sulfomucin) and columnar cells (containing acid or neutral mucin), as well as an incompletely developed brush border.…”

Section: Animal Models Of Esophageal Adenocarcinomamentioning

confidence: 99%

Esophageal Carcinogenesis

Watanabe¹,

Shimizu²,

Kochi³

et al. 2014

OJPathology

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Esophageal cancer is the sixth leading cause of cancer death and remains one of the least survivable cancers. Esophageal cancers show wide variations in incidence in different population, suggesting that environmental or lifestyle risk factors could be controlled to reduce risk of these diseases. There are two major histopathologic types (squamous cell carcinoma and adenocarcinoma) of esophageal epithelial malignancy. Recently, the rate of adenocarcinoma is increasing in developed countries: in the United States, 50% or more is adenocarcinoma and, in about 70%, the increase especially in a white male serves as adenocarcinoma. Esophageal adenocarcinoma develops in the lower esophagus. In contrast, in Japan, the increase in adenocarcinoma is not clear and most (90%) of esophageal cancers are squamous cell carcinoma. Such squamous cell carcinoma occurs onto the middle part esophagus mostly, and 60% or more of the whole esophagus cancer also develops in the middle and upper parts. These differences also influence the treatment results. The scope of this article is to discuss carcinogenesis in the esophagus by giving an overview about its histopathological characteristics and molecular mechanisms.

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Influence of surgically induced gastric and gastroduodenal content reflux on esophageal carcinogenesis – experimental model in Wistar female rats *

Cited by 21 publications

References 33 publications

NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in human hypopharyngeal cells

NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in human hypopharyngeal cells

Radiological evaluation of the patency of duodenal-esophageal anastomosis during a long postoperative follow-up: effectiveness of an alkaline reflux model in rats

Esophageal Carcinogenesis

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