Inflammation-Related Carcinogenesis and Prevention in Esophageal Adenocarcinoma Using Rat Duodenoesophageal Reflux Models

Development from chronic inflammation to Barrett’s adenocarcinoma is known as one of the inflammation-related carcinogenesis routes. Gastroesophageal reflux disease induces regurgitant esophagitis, and esophageal mucosa is usually regenerated by squamous epithelium, but sometimes and somewhere repla...

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Main Authors: Koichi Miwa, Tetsuo Ohta, Takanori Hattori, Koji Nishijima, Tomoharu Miyashita, Shozo Sasaki, Katsunobu Oyama, Takashi Fujimura
Format: Article
Language:English
Published: MDPI AG 2011-08-01
Series:Cancers
Subjects:
Online Access:http://www.mdpi.com/2072-6694/3/3/3206/
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author Koichi Miwa
Tetsuo Ohta
Takanori Hattori
Koji Nishijima
Tomoharu Miyashita
Shozo Sasaki
Katsunobu Oyama
Takashi Fujimura
author_facet Koichi Miwa
Tetsuo Ohta
Takanori Hattori
Koji Nishijima
Tomoharu Miyashita
Shozo Sasaki
Katsunobu Oyama
Takashi Fujimura
author_sort Koichi Miwa
collection DOAJ
description Development from chronic inflammation to Barrett’s adenocarcinoma is known as one of the inflammation-related carcinogenesis routes. Gastroesophageal reflux disease induces regurgitant esophagitis, and esophageal mucosa is usually regenerated by squamous epithelium, but sometimes and somewhere replaced with metaplastic columnar epithelium. Specialized columnar epithelium, so-called Barrett’s epithelium (BE), is a risk factor for dysplasia and adenocarcinoma in esophagus. Several experiments using rodent model inducing duodenogastroesophageal reflux or duodenoesophageal reflux revealed that columnar epithelium, first emerging at the proliferative zone, progresses to dysplasia and finally adenocarcinoma, and exogenous carcinogen is not necessary for cancer development. It is demonstrated that duodenal juice rather than gastric juice is essential to develop esophageal adenocarcinoma in not only rodent experiments, but also clinical studies. Antireflux surgery and chemoprevention by proton pump inhibitors, nonsteroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, green tea, retinoic acid and thioproline showed preventive effects on the development of Barrett’s adenocarcinoma in rodent models, but it remains controversial whether antireflux surgery could regress BE and prevent esophageal cancer in clinical observation. The Chemoprevention for Barrett's Esophagus Trial (CBET), a phase IIb, multicenter, randomized, double-masked study using celecoxib in patients with Barrett's dysplasia failed to prove to prevent progression of dysplasia to cancer. The AspECT (Aspirin Esomeprazole Chemoprevention Trial), a large multicenter phase III randomized trial to evaluate the effects of esomeprazole and/or aspirin on the rate of progression to high-grade dysplasia or adenocarcinoma in patients with BE is now ongoing.
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spelling doaj.art-e77da64e822e4bfea84b3641da5309be2023-09-02T14:10:26ZengMDPI AGCancers2072-66942011-08-01333206322410.3390/cancers3033206Inflammation-Related Carcinogenesis and Prevention in Esophageal Adenocarcinoma Using Rat Duodenoesophageal Reflux ModelsKoichi MiwaTetsuo OhtaTakanori HattoriKoji NishijimaTomoharu MiyashitaShozo SasakiKatsunobu OyamaTakashi FujimuraDevelopment from chronic inflammation to Barrett’s adenocarcinoma is known as one of the inflammation-related carcinogenesis routes. Gastroesophageal reflux disease induces regurgitant esophagitis, and esophageal mucosa is usually regenerated by squamous epithelium, but sometimes and somewhere replaced with metaplastic columnar epithelium. Specialized columnar epithelium, so-called Barrett’s epithelium (BE), is a risk factor for dysplasia and adenocarcinoma in esophagus. Several experiments using rodent model inducing duodenogastroesophageal reflux or duodenoesophageal reflux revealed that columnar epithelium, first emerging at the proliferative zone, progresses to dysplasia and finally adenocarcinoma, and exogenous carcinogen is not necessary for cancer development. It is demonstrated that duodenal juice rather than gastric juice is essential to develop esophageal adenocarcinoma in not only rodent experiments, but also clinical studies. Antireflux surgery and chemoprevention by proton pump inhibitors, nonsteroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, green tea, retinoic acid and thioproline showed preventive effects on the development of Barrett’s adenocarcinoma in rodent models, but it remains controversial whether antireflux surgery could regress BE and prevent esophageal cancer in clinical observation. The Chemoprevention for Barrett's Esophagus Trial (CBET), a phase IIb, multicenter, randomized, double-masked study using celecoxib in patients with Barrett's dysplasia failed to prove to prevent progression of dysplasia to cancer. The AspECT (Aspirin Esomeprazole Chemoprevention Trial), a large multicenter phase III randomized trial to evaluate the effects of esomeprazole and/or aspirin on the rate of progression to high-grade dysplasia or adenocarcinoma in patients with BE is now ongoing.http://www.mdpi.com/2072-6694/3/3/3206/inflammation-metaplasia-adenocarcinoma sequenceBarrett’s esophagusduodenogastroesophageal refluxchemoprevention for esophageal adenocarcinomaantireflux surgeryproton pump inhibitorsnonsteroidal anti-inflammatory drugsselective cyclooxygenase-2 inhibitorsthioproline
spellingShingle Koichi Miwa
Tetsuo Ohta
Takanori Hattori
Koji Nishijima
Tomoharu Miyashita
Shozo Sasaki
Katsunobu Oyama
Takashi Fujimura
Inflammation-Related Carcinogenesis and Prevention in Esophageal Adenocarcinoma Using Rat Duodenoesophageal Reflux Models
Cancers
inflammation-metaplasia-adenocarcinoma sequence
Barrett’s esophagus
duodenogastroesophageal reflux
chemoprevention for esophageal adenocarcinoma
antireflux surgery
proton pump inhibitors
nonsteroidal anti-inflammatory drugs
selective cyclooxygenase-2 inhibitors
thioproline
title Inflammation-Related Carcinogenesis and Prevention in Esophageal Adenocarcinoma Using Rat Duodenoesophageal Reflux Models
title_full Inflammation-Related Carcinogenesis and Prevention in Esophageal Adenocarcinoma Using Rat Duodenoesophageal Reflux Models
title_fullStr Inflammation-Related Carcinogenesis and Prevention in Esophageal Adenocarcinoma Using Rat Duodenoesophageal Reflux Models
title_full_unstemmed Inflammation-Related Carcinogenesis and Prevention in Esophageal Adenocarcinoma Using Rat Duodenoesophageal Reflux Models
title_short Inflammation-Related Carcinogenesis and Prevention in Esophageal Adenocarcinoma Using Rat Duodenoesophageal Reflux Models
title_sort inflammation related carcinogenesis and prevention in esophageal adenocarcinoma using rat duodenoesophageal reflux models
topic inflammation-metaplasia-adenocarcinoma sequence
Barrett’s esophagus
duodenogastroesophageal reflux
chemoprevention for esophageal adenocarcinoma
antireflux surgery
proton pump inhibitors
nonsteroidal anti-inflammatory drugs
selective cyclooxygenase-2 inhibitors
thioproline
url http://www.mdpi.com/2072-6694/3/3/3206/
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