PDTM-02. STRESS GRANULES ARE INDUCED BY OXIDATIVE STRESS IN PEDIATRIC BRAIN TUMORS AND PREDICT POOR OUTCOME
Bibliographic record
Abstract
BACKGROUND/OBJECTIVES: Brain tumors represent the most common and aggressive pediatric cancer type, underscoring a dire need for novel therapeutic approaches. Tumors are continually exposed to acute changes in their microenvironment, including oxidative stress. To overcome acute stress, cells form stress granules (SGs), clusters of RNA and RNA-binding proteins (RBPs) that rapidly alter the cellular mRNA translation landscape. Preliminary data indicate that pharmacological inhibition of SG formation blocks the antioxidant response of the transcription factor NRF2 (NFE2L2), impairing pediatric sarcoma invasive and metastatic capacity. We therefore set out to determine if pediatric brain tumors rely on SGs to overcome oxidative stress, and if targeting SGs could represent a therapeutic approach for these tumors. We analyzed public databases for links between mRNA expression of the RBP G3BP1 and NFE2L2. Immunohistochemistry (IHC) for G3BP1, NRF2 and oxidative stress markers (4HNE) was performed on atypical theratoid rabdoid tumor (AT/RT), pediatric glioblastoma (pGBM) and ependymoma (EPN) tissue microarrays. AT/RT, pGBM and EPN cell lines were treated with NaAsO2 and H2O2 to induce oxidative stress and SG presence was determined by ImmunoFluorescence for the RBPs G3BP1 and TIA-1. G3BP1 and NFE2L2 expression positively correlates in several pediatric tumor cohorts, including AT/RT, pGBM and EPN (p<0.01). IHC not only confirmed mRNA results, but revealed that G3BP1 over-expression is linked to higher WHO grade and recurrent disease in EPN. High G3BP1 levels are also predictive of poor outcome in pGBM (p<0.05). Finally, oxidative stress induces the RBPs G3BP1 and TIA-1 to form SGs in vitro. CONCLUSIONS: SGs represent an important mediator for the adaptive response of pediatric brain tumors to acute oxidative stress. Inhibiting SG formation might therefore constitute a therapeutic approach for AT/RT, pGBM and EPN. Future studies will aim at confirming the efficacy of drugs that inhibit SG formation in pediatric brain tumors.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.002 | 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".