Abstract CT112: A multi-mineral approach to alter biomarkers of growth and differentiation in the human colon: Results from an interventional trial

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Abstract Introduction: Based on pre-clinical studies, it was hypothesized that a calcium- and multiple trace element-rich product- Aquamin will promote differentiation/barrier function and reduce proliferation in the human colonic epithelium more effectively than calcium alone. The goal of the study is to begin testing this hypothesis. Methods: A 90-day interventional trial was conducted with human subjects (at risk for colorectal cancer). Thirty subjects were enrolled and randomized to receive Aquamin or calcium alone (each providing 800 mg/day) or placebo. Prior to ingesting the study-agents and following the course of treatment, colon biopsies were obtained by sigmoidoscopy and examined for markers of growth, and differentiation by quantitative immunohistochemistry. Tandem mass tag mass spectrometry-based proteomic screen was used to obtain a broad comparison of protein alterations induced by Aquamin as compared to calcium and placebo. Specimens were pooled by the group and for each group, a pre-, post-treatment “ordinate” was obtained to determine proteins that were up-regulated or down-regulated in the post-treatment specimens as compared to pre-treatment. Results: Quantitation of proliferation marker Ki67 showed a 21% decrease in post-intervention expression with Aquamin to its pre-intervention expression. In contrast, there was no change in differentiation marker (CK20) expression. Calcium did not reduce Ki67 expression (Table). When crypt length was measured, there was no change in the post-intervention biopsies (in all groups), indicating no adverse effect of any intervention on the colonic tissue. On proteomic screen, there was minimal up- and down-regulation of proteins in placebo-treated subjects. In contrast, a large number of proteins demonstrated up- or down-regulation with calcium and Aquamin (at 1.8-fold and <2% FDR). The proteomic screen demonstrated strong up-regulation of the major non-collagenous components of the basement membrane (laminin- α, β, γ and perlecan), CEACAM1, mucin-2 and several keratins in response to Aquamin. Ki67 protein was downregulated with Aquamin. Table.Quantitation of Proliferation and Differentiation Markers.PlaceboCalciumAquaminPrePostPrePostPrePostKi67Positive percent nuclei13.1±5.212.7±4.112.1±3.913.9±5.816.6±8.113.1±4.7Positive nuclei / mm2264±119229±89234±79262±117309±191222±105CK20Positive pixel count0.44±0.260.46±0.240.47±0.170.51±0.170.54±0.210.54±0.18Crypt Length (µm)351±71354±72349±67348±86350±81372±79 Conclusion: These results suggest that trace elements in conjunction with calcium can reduce proliferation and improve barrier in the colon epithelium more effectively than calcium alone. This study provides biomarker data needed to plan a more definitive clinical interventional (polyp-prevention) trial. Citation Format: Muhammad N. Aslam, Shannon McClintock, Karsten Knuver, Mohamed Ali H. Jawad-Makki, Haris Ahmad, Danielle (Kim) Turgeon, James Varani. A multi-mineral approach to alter biomarkers of growth and differentiation in the human colon: Results from an interventional trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT112.