Anti-inflammatory chemoprevention attenuates the phenotype in a mouse model of esophageal adenocarcinoma

Barrett´s Esophagus (BE) is the main known precursor condition of Esophageal Adenocarcinoma (EAC). BE is defined by the presence of metaplasia above the normal squamous columnar junction and has mainly been attributed to gastroesophageal reflux disease (GERD) and chronic reflux esophagitis. Thus, the rising incidence of EAC in the Western world is likely mediated by chronic esophageal inflammation, secondary to GERD in combination with environmental risk factors such as a Western diet and obesity. However, (at present) risk prediction tools and endoscopic surveillance have shown limited effectiveness. Chemoprevention as an adjunctive approach remains an attractive option to reduce the incidence of neoplastic disease. Here, we investigate the feasibility of chemopreventive approaches in BE and EAC via inhibition of inflammatory signaling in a transgenic mouse model of BE and EAC (L2-IL1B mice), with accelerated tumor formation on a high fat diet (HFD). L2-IL1B mice were treated with the IL-1 receptor antagonist Anakinra and the nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin or Sulindac. Interleukin-1b antagonism reduced tumor progression in L2-IL1B mice with or without a HFD, while both NSAIDs were effective chemoprevention agents in the accelerated HFD fed L2-IL1B mouse model. Sulindac treatment also resulted in a marked change in the immune profile of L2-IL-1B mice. In summary, anti-inflammatory treatment of HFD-treated L2-IL1B mice acted protectively on disease progression. These results from a mouse model of BE support results from clinical trials that suggest that anti-inflammatory medication may be effective in the chemoprevention of EAC.      «

Barrett´s Esophagus (BE) is the main known precursor condition of Esophageal Adenocarcinoma (EAC). BE is defined by the presence of metaplasia above the normal squamous columnar junction and has mainly been attributed to gastroesophageal reflux disease (GERD) and chronic reflux esophagitis. Thus, the rising incidence of EAC in the Western world is likely mediated by chronic esophageal inflammation, secondary to GERD in combination with environmental risk factors such as a Western diet and obesit...     »

BayBioMS; anti-inflammatory agentsaspirinobesityphenotypesignal transductioninterleukin-1interleukin-1 receptor antagonistschemopreventionesophageal adenocarcinomaesophagitisendoscopyenvironmental factorsgastroesophageal reflux diseaseanti-inflammatory agents, non-steroidaldisease progressionpeptic esophagitismetaplasiamice, transgenicsulindacwestern worldesophagusmiceneoplasmsanakinragastro-esophageal reflux disease with esophagitisinterleukin-1 betasurveillance, medicalchemopreventive agentstumor progressiondiet, westerndiet, high-fat     «

BayBioMS; anti-inflammatory agentsaspirinobesityphenotypesignal transductioninterleukin-1interleukin-1 receptor antagonistschemopreventionesophageal adenocarcinomaesophagitisendoscopyenvironmental factorsgastroesophageal reflux diseaseanti-inflammatory agents, non-steroidaldisease progressionpeptic esophagitismetaplasiamice, transgenicsulindacwestern worldesophagusmiceneoplasmsanakinragastro-esophageal reflux disease with esophagitisinterleukin-1 betasurveillance, medicalchemopreventive agentst...     »