EXTH-80. ENHANCED THERAPEUTIC RESPONSE IN MURINE MEDULLOBLASTOMA TUMOR MODEL USING ADENANTHIN AND TRANSIENT MODULATION OF THE BLOOD-BRAIN BARRIER WITH CADHERIN PEPTIDE
Bibliographic record
Abstract
Peroxiredoxin1 (PRDX1) is overexpressed in medulloblastoma (MBL) causing resistance to therapy. Adenanthin (PRDX1 inhibitor) had been validated as a therapeutic target in MBL. However, adenanthin does not cross the blood-brain barrier (BBB). The objective of this study was to examine the efficacy of adenanthin in conjunction with Hav peptide (to transiently modulate the BBB) in an MBL tumor model. Effects of HAV6 on BBB permeability to gadolinium contrast-agent (Gd-DTPA) and adenanthin were examined in healthy mice using MRI and LC/MS respectively. The response of MBL tumor mice to adenanthin was also examined under control conditions and following the BBB disruption using HAV6. Brain tumors in mice were induced by stereotaxic injection of D425 tumor cells. A 5-cycle treatment regimen began 10 days following tumor induction. For each cycle, the mice received 3-consecutive days of either vehicle, adenanthin (10mg/kg), or a combination of adenanthin (10mg/kg) and Hav (0.010mmol/kg) peptide followed by a 1 day of rest. The mice were then monitored for signs of tumor progression. Under control conditions, very little Gd-DTPA and adenanthin entered the brain. In contrast, mice treated with HAV6 showed a significant increase of BBB permeability to both Gd-DTPA (3-fold) and adenanthin (100-fold) compared to control. All mice injected with D425 cells developed tumors within 7 days as seen by bioluminescence imaging. Tumor volume increased at similar rate with median survival of 16 and 18 days for placebo and adenanthin treatment groups respectively. In contrast, tumor bearing mice treated with the combination of Hav and adenanthin showed significant reduction in tumor size and extended survival (>32 days) with little to no symptoms of tumor burden or toxicity related to treatment. Transient disruption of BBB using HAV6 provided therapeutically relevant adenanthin brain concentrations, thereby improving the response to treatment in tumor bearing mice.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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".