PDTM-48. PEROXIREDOXIN1 IS A THERAPEUTIC TARGET IN GROUP-3 MEDULLOBLASTOMA
Bibliographic record
Abstract
Group-3 medulloblastoma (MBL), one of the most common malignant pediatric brain tumors, is highly resistant to radiation and chemotherapy and have the worst prognosis. Hence, there is an urgent need to elucidate targets that can sensitize these tumors to conventional chemotherapy and radiation. We identified PRDX1 as therapeutic candidate in Group-3 MBL. Inhibition of PRDX1 using Adenanthin or RNAi led to radiation sensitization in D425-med cells when compared to controls. Over expression of PRDX1 in SHH- group (Daoy cells) resulted in radiation resistance. Targeting PRDX1 resulted in extensive oxidative DNA damage and induction of apoptosis. Nude mice with Group-3 MBL flank tumors when treated with Adenanthin had significant decrease in tumor volume and survived longer. Mice bearing orthotopic tumors from patient derived xenografts / Group-3 MBL cells with diminished PRDX1 expression or PRDX1 inhibition by Adenanthin survived longer when compared to controls. We also correlated PRDX1 expression to patient outcomes in a validated Medulloblastoma tumor microarray (TMA). We performed next generation whole genome sequencing to identify pathways that are affected with PRDX1 inhibition or silencing. The results from these experiments will be presented. Our results suggest that PRDX1 is a therapeutic target in all sub-groups of medulloblastoma and Adenanthin could be used as a radio-sensitizer in the treatment of Group-3 MBLs.
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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) | 0.001 | 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".