English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

An urgent need exists to identify efficacious therapeutic preventive interventions for individuals who are at high risk of developing colorectal cancer. To maximize the benefits of preventive intervention, it is vital to identify the time interval during which the initiation of a preventive intervention will lead to an optimal outcome. The goal of the present study was to determine if oncogenic events can be detected in the nonneoplastic colonic mucosa of  Apc +/Min-FCCC   mice prior to formation of the first adenoma, thus defining an earlier point of intervention along the cancer continuum. Tissues taken at three potential points of intervention were characterized: prior to  Apc  mutation (wild type  Apc +/+-FCCC   mice); after initiation but prior to colon adenoma formation (tumor-free  Apc +/Min-FCCC   mice); and after formation of the first colon adenoma (tumor-bearing  Apc +/Min-FCCC   mice). Experimentation focused on molecular processes that are dysregulated in early colon lesions: 1) cellular proliferation (proliferative index and size of the proliferative zone); 2) cellular stemness (expression of  Ascl2 ,  Grem1 ,  Lgr5  and  Muc2 ); 3) EGFR signaling (expression of  Ereg ); and 4) inflammation (expression of  Mmp9 ,  Ptsg2 , and  Reg4 , as well as secretion of 18 cytokines involved in immune activation and response). Interestingly, the nonneoplastic colonic mucosa of wild type, tumor-free  Apc +/Min-FCCC  , and tumor-bearing  Apc +/Min-FCCC   mice did not display significant differences in average epithelial cell proliferation (fold change 0.8–1.3, p≥0.11), mucosal gene expression (fold change 0.8–1.4, p≥0.22), or secretion of specific cytokines from colonic mucosa (fold change 0.2–1.5, p≥0.06). However, the level of cytokine secretion was highly variable, with many (22% of wild type, 31% of tumor-free  Apc +/Min-FCCC  , and 31% of tumor-bearing  Apc +/Min-FCCC  ) mice categorized as outliers (> 1.5 x interquartile ranges below the first quartile or above the third quartile) due to elevated expression of at least one cytokine. In summary, no differences were observed in proliferation, stemness, and EGFR signaling in the colonic mucosa of wild type vs  Apc +/Min-FCCC   mice, with low baseline cytokine expression, prior to the formation of the first colon adenoma. The results of this study provide valuable baseline data to inform the design of future cancer prevention studies.

frontiers in oncology

High Variability in Cellular Proliferation, Gene Expression, and Cytokine Production in the Nonneoplastic Colonic Epithelium of Young Apc+/Min-FCCC Mice