Abstract 1976: Monocytic/macrophagic differentiation status of human promyelocytic leukemia cells dictates targeting efficacy of NF-kappaB downstream gene productes
Bibliographic record
Abstract
Abstract Disruption of the endothelial blood-brain barrier (BBB) facilitates the translocation of circulating microbes and immune cells. As a consequence, secondary cerebral infections and development of brain pathologies may occur. Enhanced transendothelial migration of HL-60-derived macrophages was recently demonstrated, but the intrinsic signalling mechanisms involved poorly documented. In this study, we investigated NF-kB signalling pathway targets associated with phorbol 12-myristate 13-acetate (PMA)-induced promyelocytic HL-60 differentiation into macrophages. Given that the inhibition of matrix metalloproteinase (MMP)-9 and of cyclooxygenase (COX)-2 limits BBB disruption, we also investigated the efficacy of the chemopreventive and dietary-derived epigallocatechin-3-gallate (EGCG) molecule on the NF-kB-mediated transcriptional regulation of a panel of 89 biomarkers including MMP-9 and COX-2. PMA-induced HL-60 cell differentiation and adhesion were reflected by IkB degradation, a signalling process that was reversible by EGCG. Using gene expression arrays, we identified moderately-to-highly expressed NF-kB gene targets associated with HL-60 differentiation process, among which EGCG was able to efficiently inhibit gene and protein MMP-9 and COX-2 expression. In contrast, EGCG was not only inefficient in reversing some PMA-induced NF-kB genes in terminally-differentiated macrophages but rather showed selective antagonism towards COX-2 expression while that of MMP-9 still remained high. Decreased expression of the 67 kDa Laminin Receptor in terminally-differentiated macrophages may contribute to such differential EGCG efficacy. Our results suggest that MMP-9-mediated BBB disruption may be prevented by EGCG only during procarcinogenic processes that trigger HL-60 macrophagic differentiation. Terminally-differentiated macrophage transendothelial migration associated to neuroinflammation may however not be pharmacologically affected by such a specific class of chemopreventive flavonoid. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1976. doi:1538-7445.AM2012-1976
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".