AI Article Synopsis
- * Researchers studied the effects of sulindac on colorectal stem cell dynamics by analyzing methylation patterns in tissue samples from treated and placebo groups, finding a notable reduction in clonal evolution in the sulindac group.
- * The study suggests that changes in tag diversity over time can be linked to the number of polyps, indicating that this measurement may serve as a useful predictive biomarker for the drug's chemopreventive effects.
Article Abstract
The non-steroidal anti-inflammatory drug sulindac decreases size and number of adenomas after 4-6 months of treatment for familial adenomatous polyposis (FAP) patients. However, the underlying mechanism remains unknown. As stem cells are thought to be the tumor precursor cells, visualizing their behavior is crucial for monitoring tumor progression. Increased tag diversity in inactive genes is indicative of a protracted clonal evolution and consequently, increased risk for tumor formation. Therefore, the effect of sulindac on stem cell dynamics was studied. Normal appearing single crypts were laser microdissected in placebo- and sulindac- treated FAP patient tissue after which the methylation patterns were visualized by Next Generation Sequencing. A significant difference in tag diversity over time was found in the sulindac group compared to the placebo group (*p = 0.018), indicative of a shortened clonal evolution treated sulindac. The rate of change in tag diversity over time was correlated with polyp number change over time. No significant difference over time was observed in the percent methylation when comparing placebo vs sulindac. In conclusion, daily sulindac administration in FAP patients significantly altered colorectal stem cell dynamics, which might explain the chemopreventive action of this drug indicating that tag diversity may be used as a predictive biomarker.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607292 | PMC |
| http://dx.doi.org/10.1038/s41598-017-11865-y | DOI Listing |
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