Targeting Cyclooxygenase-2 Reduces Overt Toxicity toward Low-Dose Vinblastine and Extends Survival of Juvenile Mice with Friend Disease
Bibliographic record
Abstract
PURPOSE: To test the efficacy of selective therapy against cyclooxygenase-2 in combination with a low-dose regimen of a cytotoxic agent in the treatment of juvenile hematopoietic malignancies in the experimental model, Friend disease. EXPERIMENTAL DESIGN: Juvenile erythroleukemic mice (n = 8) received no treatment, celecoxib (1600 mg/kg/d), vinblastine (0.5 microg/g twice weekly), vehicle controls, or celecoxib + vinblastine combination (n = 9) over a 6-month period from time of tumor induction. Overt toxicity was assessed daily and recorded weekly. RESULTS: Among randomly selected mice from celecoxib treatment groups, plasma concentrations ranged from 2 to 6 micromol/L. As a single agent, celecoxib was not associated with any apparent toxicity. Monotherapy with vinblastine, however, caused early mortality marked by severe diarrhea, lethargy, and weight loss. At the tested doses, neither vinblastine nor celecoxib enhanced survival as monotherapies. Coadministration of these two drugs alleviated the overt toxicity associated with vinblastine and resulted in a significant increase in survival (P < 0.05). Survivors sampled throughout the study showed a trend to decreased weight loss and hematocrit levels among all groups, but significance was evidenced earlier in the vinblastine monotherapy group overall (P < 0.05). Despite similar degree of splenomegaly, histologic analysis revealed preserved splenic mantle architecture from mice given combination therapy compared with those sampled from mice on all other monotherapies, exhibiting a more diffuse burden of blasts and destruction of germinal centers. CONCLUSION: We propose that addition of a selective cyclooxygenase-2 inhibitor to a modified low-dose conventional chemotherapeutic regimen protects juvenile mice with Friend disease from succumbing to low-dose cytotoxicity, in part, by neutralizing acute inflammatory responses.
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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".