In Vitro Risk Assessment of a Nanoparticulate Formulation of Arsenic Trioxide in Isolated Ovarian Follicles Is Representative of Effects In Vivo.
Bibliographic record
Abstract
We report here the first methods to assess the fertotoxicity of chemotherapeutic drugs in both in vitro and in vivo systems. Using a novel nanoparticulate formulation of arsenic trioxide (ATO), [NB(Ni,As)] encapsulated in liposomal vesicles, that has preclinical efficacy in both lymphoid and breast tumors, ovarian follicles were assessed for uptake of free arsenic and was shown to have lower arsenic content than using ATO alone. Arsenic induced toxicity to the female reproductive tract was examined using isolated, ovarian, secondary follicles embedded in a degradable fibrin-alginate matrix and found that healthier follicles degraded fibrin at an advanced rate compared to unhealthy follicles seen after ATO treatment. The serum and ovarian pharmacokinetics were measured for NB(Ni,As) and ATO in mice and while the serum levels (AUC) are drastically increased for NB(Ni,As) compared with ATO, the ovarian uptake is reduced. Extended dosage studies revealed that the NB(Ni,As) was not detrimental on the ovary unlike ATO, which resulted in constant diestrus. Ovarian tissue displayed normal histology from NB(Ni,As) treated mice however ATO treatment revealed numerous hemorrhagic ovarian cysts. In short, we have validated a novel series of assays to determine the fertotoxicity of chemotherapetuic agents, and demonstrated that the NB(Ni,As) has reduced toxicity to the female reproductive tract in mice compared with free drug. This is the first known test for chemotherapeutic fertotoxicity and could be adapted for use in human to aid in the development of fertoprotective chemotherapeutics. (poster)
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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 | 0.001 | 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".