On the Synergistic Effect of Doxorubicin and Mitomycin C Against Breast Cancer Cells
Bibliographic record
Abstract
The combination of doxorubicin and mitomycin C has been shown previously to result in supra-additive tumor cell killing in vitro in both murine and human breast cancer cells and in vivo against murine breast cancer cells. Median effect analysis was used to determine the significance and degree of interaction. The origin of this synergy was sought by evaluating the contribution of membrane efflux pump modulation, formaldehyde production, reactive oxygen species, DNA cross-linking, and DNA double-strand breaks to this effect. The interaction of mitomycin C and doxorubicin in vitro was found to be a true synergy whose mechanism was efflux pump-independent. DNA cross-links were only found to increase additively with co-administration of the drugs; however, a supra-additive increase in DNA double-strand breaks was observed. The results suggest that poisoning of topoisomerase IIalpha by doxorubicin may interact with drug-induced DNA cross-links to enhance the formation of DNA double-strand breaks. This interaction, together with glutathione depletion and mitomycin C-derived formaldehyde, may be the underlying mechanism(s) of the synergy observed between mitomycin C and doxorubicin.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".