Azole‐based heme oxygenase inhibitors and their effects on AC2M2 mouse breast cancer growth and metastasis in vivo
Bibliographic record
Abstract
Heme oxygenase (HO) catalyzes the breakdown of heme to biliverdin, free iron, and carbon monoxide. The two major isoforms, HO‐1 (inducible) and HO‐2 (constitutive), are involved in a variety of physiological functions, including apoptosis, inflammation and angiogenesis ‐ important in the growth of some types of cancer. Previous work using metalloporphyrin‐based compounds identified HO inhibition as a potential therapy for some cancers. These compounds are limited by their lack of selectivity for HO and inhibit other heme‐dependent enzymes. Novel azole‐based HO inhibitors have demonstrated increased in vitro selectivity for HO and were tested for their effects on breast cancer growth & progression. In vitro experiments included observing the effects on AC2M2 cell viability and endothelial tube growth in an aortic ring model. In vivo experiments involved the implantation of AC2M2 cells into the mammary fat pad of female nude mice, which then received metronomic treatment with an azole‐based compound or vehicle. Primary tumours were removed on day 21 and metastases grew for another 14 days. Based on previous results, we hypothesized that the azole‐based HO inhibitors would decrease primary tumour volume and decrease the incidences of lung metastases, when compared to control. The findings will help determine whether HO is an appropriate target in the treatment of breast cancer. (Funded by the Ontario Institute of Cancer Research 08NOV‐142; MH is the recipient of a Fellowship from the Canadian Breast Cancer Foundation ‐ Ontario Region)
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".