A89 EMERGING THERAPEUTIC TARGETS FOR INFLAMMATORY BOWEL DISEASE-COLORECTAL CANCER: CASE STUDY ANALYSIS
Bibliographic record
Abstract
Persistent inflammation can trigger altered epigenetic, inflammatory and bioenergetics states. Inflammatory bowel disease (IBD) is a heterogeneous disease with an abnormal inflammatory state and subsequent metabolic syndrome disorder with abnormal leptin and alterations in the metabolic kinase, AMP-activated protein kinase (AMPK). Altered inflammation in IBD has been well studied and > 90% of current IBD therapeutics are directed to inhibiting altered inflammatory elements that drive inflammation of the epithelial cells of the colonic crypt. We hypothesize that to completely resolve mucosal inflammation we must (i) Inhibit inflammatory mediators (of which RIPK2 is a key player) and (ii) resolve secondary effects of inflammation such a reset of metabolic dysfunction (of which AMPK is key player). If these are not resolved in a timely manner, predisposition to the malignant state will occur The aims of this study are to explore correlations between key inflammatory/metabolic markers, clinical severity of disease and malignant transformation in 4 case study IBD-CRC patients to uncover emerging new therapeutic players. AMPK and RIPK2 activity will be tracked with phosphospecific antibodies. Immunohistochemistry and immunoblotting carried out as described by Gordon et al., PLOSone 2013. All patients have been consented under our IBD ethics protocol (Pro00001523 and Pro00077868). Using longitudinal tissue sections from IBD-CRC case study patients, we explored the expression/activation levels of markers of epigenetic change (RASSF1A), inflammation (the obligate NOD2 kinase, RIPK2) and metabolism (AMPK) in order to gain insight into molecular drivers of disease. We confirm that the loss in the activity of AMPK and gain of activity of RIPK2 drives the inflammatory phenotype of the gut leading into the cancer state. Interestingly, active RIPK2 remains elevated in patients in patients that were undergoing IBD therapeutics. These results suggest that directed therapeutics to RIPK2 may be a useful combination therapy to eliminate a robust driver of inflammation and malignant transformation. Additional correlations will be presented. None
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".