Proposal for an Organ-Specific Chronic Inflammation–Remodeling–Carcinoma Sequence

Abstract

An organ-specific chronic inflammation-remodeling-carcinoma sequence has been proposed, mainly for the alimentary tract. As representative diseases, gastroesophageal reflux disease, chronic gastritis and inflammatory bowel disease (ulcerative colitis and Crohn's disease of the colitis type) were adopted for this discussion. Tissue remodeling is such an important part of tumorigenesis in this sequence that an organ-specific chronic inflammation-remodeling-carcinoma sequence has been proposed in detail. Chronic inflammation accelerates the cycle of tissue injury and regeneration; in other words, cell necrosis (or apoptosis) and proliferation result in tissue remodeling in long-standing cases of inflammation. Remodeling encompasses epithelial cell metaplasia and stromal fibrosis, and modifies epithelial-stromal cell interactions. Further, the accumulation of genetic, epigenetic and molecular changes-as well as morphologic disorganization-also occurs during tissue remodeling. The expression of mucosal tissue adapted to chronic inflammatory injury is thought to occur at an early stage. Subsequently, dysplasia and carcinoma develop on a background of remodeling due to continuous, active inflammation. Accordingly, organ-specific chronic inflammation should be ameliorated or well controlled with appropriate monitoring if complete healing is unachievable.

Role of Obesity, Physical Exercise, Adipose Tissue-Skeletal Muscle Crosstalk and Molecular Advances in Barrett’s Esophagus and Esophageal Adenocarcinoma

“…Chronic inflammation associated with epithelial metaplasia, present in BE, increases cancer risk, presumably favoring the tumor microenvironment and tumor progression [ 140 , 141 , 142 ]. In a pathologically modified VAT, the release of increased amounts of the pro-inflammatory cytokines [ 143 , 144 ] and an enhancement of plasma levels of pro-inflammatory adipokines in BE patients have also been observed [ 135 , 145 , 146 , 147 , 148 , 149 , 150 ].…”

Hotspots and Frontiers in Inflammatory Tumor Microenvironment Research: A Scientometric and Visualization Analysis

“…The formation of the inflammatory tumor microenvironment is caused by external factors, like tobacco ( Giotopoulou and Stathopoulos, 2020 ), alcohol ( LoConte et al, 2018 ), and obesity ( Iyengar et al, 2016 ) as well as other factors, such as gut microbiota ( Yang et al, 2021 ) and exercise ( Hojman et al, 2018 ). Several mechanisms, such as the production of cytokines ( Atretkhany et al, 2016 ), pro-inflammatory mediators ( Alspach et al, 2019 ; Laha et al, 2021 ), angiogenesis ( Zhou et al, 2021 ), and tissue remodeling ( Okayasu et al, 2019 ), associated with the inflammatory tumor microenvironment have been reported ( Comen et al, 2018 ). However, the main progresses and insights of this field have not been effectively identified and comprehensively explored.…”