The effect of sodium thiosulfate on the metabolism of cis-platin in human plasma in vitro
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
The anticancer drug cis-platin (CP) is widely used to treat patients, but it is also associated with significant side effects, including nephrotoxicity. Given that this metallodrug is intravenously (iv) administered, its biotransformations in the bloodstream are likely to be involved in mediating these side-effects. Previous studies have revealed that the iv administration of patients/mammalian model organisms with sodium thiosulfate (STS) can ameliorate the side effects of CP, but the underlying molecular basis remains elusive. We have studied the effect of STS on the metabolism of CP in human plasma in vitro by determining the platinum (Pt) distribution using size exclusion chromatography (SEC) coupled on-line to an inductively coupled plasma atomic emission spectrometer (ICP-AES). The addition of STS to plasma 10 min before CP was added accelerated the hydrolysis of CP and resulted in the formation of a Pt-STS complex. Conversely, when plasma was incubated with CP for up to 3 h and STS was added thereafter the analysis of the obtained mixture revealed that the formation of the same Pt-STS complex which in turn greatly diminished the plasma protein binding of CP-derived hydrolysis products. Thus, the observed amelioration of the side effects of CP by STS can be rationalized in terms of the rapid formation of a biologically inactive Pt-STS complex in the bloodstream. This is the first mechanism that can explain the amelioration of the side effects of CP by STS. Based on the fact that cis-platin remained in plasma for a considerable amount of time, the optimization of the administration sequence, the molar ratio and the time delay between the administration of both drugs emerges as a viable strategy to achieve a careful balance between ameliorating the side effects while leaving the antitumour activity intact. Our results demonstrate that in vitro studies can be useful to develop feasible strategies to mitigate the side-effects of Pt-based anticancer drugs in patients.
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.
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 | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 it