PTPS-20THE GD3 ACETYLATION PATHWAY AS A POTENTIAL THERAPEUTIC TARGET FOR PAEDIATRIC MEDULLOBLASTOMA
Bibliographic record
Abstract
Medulloblastoma (MB), the most common malignant paediatric brain tumour, is associated with high mortality rates. Survivors frequently suffer from low quality-of-life as a result of aggressive treatment. Genomic studies have led to novel classification of molecularly and clinically distinct subgroups and are paving the way for novel targeted therapies. GD3, an oncofoetal ganglioside is re-expressed in some cancers of the neural crest. GD3, central to cell movement in developing brain, is internalised during maturation of residual supernumerary cells leading to cell death. When GD3 is re-expressed in cancers, the intracellular form of GD3 is acetylated (GD3A) and is thought to protect cells from mitochondrially-mediated apoptosis. Sialate-O-acetylesterase (SIAE) is responsible for cleaving the acetyl group from GD3A. A genome-wide transcriptional analysis of 103 MB patients revealed that this enzyme is significantly down-regulated in MB tissue compared to non-neoplastic foetal and adult brain (p > 0.02). This suggests that GD3A may be deacetylated at low levels and thus the balance of GD3 to GD3A favours GD3A. Using flow cytometry to examine expression, results revealed that in MB cell lines RES256 and UW402 GD3A expression was higher (84.5% and 74.5%) than GD3 (56.6% and 61.3%) The fluorescent intensity of GD3A expression was 9.9 and 11.4 fold higher and GD3, 4.4 and 6.1 fold higher than negative controls. Immunocytochemical results were in agreement, providing additional evidence that these cells have a balance in favour of GD3A. Previous studies from our group have shown that cell surface expression of GD3 correlates with invasion and in MB cell lines tested surface expression was 31.7% and 65.7% compared to GD3A (29.5% and 11.5%). Inducible SIAE and SIAE catalytically mutated cell lines have been generated and verified in protein and esterase activity assays and will be used to evaluate this pathway as a potential therapeutic target for MB.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".