MB-48PEROXIREDOXIN 1 IS A POTENTIAL THERAPEUTIC TARGET IN GROUP-3 MEDULLOBLASTOMAS
Bibliographic record
Abstract
The poor prognosis of Group-3 medulloblastomas is associated with its resistance to conventional therapeutic strategy of radiation and chemotherapy. Thus, there is an urgent need to elucidate targets that render these tumors sensitive to conventional approaches. We identified Peroxiredoxin1 (PRDX1) as a candidate therapeutic target to radio-sensitize Group-3 medulloblastomas. We hypothesized that targeting PRDX1 in Group-3 medulloblastoma cells would induce oxidative stress and sensitize them to ionizing radiation. Accordingly, Group-3 medulloblastoma (D425-Med) cells treated with Adenanthin, a small molecule inhibitor of PRDX1, were hypersensitive to radiation when compared to controls. Similar results were observed when PRDX1 expression was down regulated using RNAi. Mechanistically, targeting PRDX1 resulted in an increase in reactive oxygen species, oxidative DNA damage as indicated by surrogate markers γ-H2A.X and 53BP1, and an induction of the apoptotic pathway when compared to controls. Athymic nude mice with flank tumors of D425-Med cells that received Adenanthin (10mg/kg body weight) presented decreased tumor growth and survived longer than the control group that received placebo. Ongoing experiments using orthotopic murine models of Group-3 medulloblastoma in which PRDX1 is targeted using RNAi or Adenanthin will help us further validate our hypothesis that PRDX1 is a potential therapeutic target in these tumors. Our preliminary data strongly suggests that PRDX1 is a potential therapeutic target that sensitizes Group-3 medulloblastomas to ionizing radiation. The results from these experiments will be presented in this meeting.
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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) | 0.001 | 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".