Metabonomic study of the hypothyroidism effect of sunitinib, a multiple inhibitor of tyrosine kinase receptors, by metabonomic approach in the rat.
Bibliographic record
Abstract
Exploration of the hypothyroidic effect of Sunitinib, a tyrosine kinase receptor inhibitor, by metabolomic approach, in the rat Renal cell carcinoma is one of the most common and deadly cancer. This cancer suffers of an extremely poor prognosis due to its low survival rate in the long term and the incidence of metastasis. To date, there is no successful treatment although a multi-targeted receptor tyrosine kinase inhibitor, Sunitinib, gives significant results thanks to a strong antiangiogenic activity blocking the tumor development. Among the numerous side effects, some (hypertension, hypothyroidism and feet/hands syndrome) are correlated with an improved efficcacy of treatment in patients presenting those adverse effects. It is therefore mandatory to understand the cellular mechanisms of this Sunitinib-induced hypothyroidism, not yet clarified today, in order to establish the link between treatment efficacy and such a side effect. In order to obtain an overview of the overall changes induced by Sunitinib, the use of metabonomic seems to be the best choice. Indeed, this recent approach allows to establish the complete metabolic profiles of an individual from his biofluids. These profiles are obtained from spectroscopic techniques combined to multivariate data analysis. The main objectives of this work was first to establish a metabonomic urinary signature of an animal model of hypothyroidism induced by exposure to propyl-thiouracil and, next, to compare this signature with the metabonomic profile of animals daily exposed to pharmacological doses of Sunitinib. Finally, this study also tried to assess the contribution of a pre-existing hypothyroidism on the effects of Sunitinib. During the experimental study, several physiological parameters were also measured. The metabonomic signature of propyl-thiouracil -induced hypothyroidism showed significant decreases in the activity of the Krebs cycle and in the urinary excretion of taurine. These changes were also observed in rats with normal thyroid function when chronically exposed to Sunitinib demonstrating the hypothyroidian effect of this drug. Similar changes were finally recorded in animals with pre-existing hypothyroidism and exposed to Sunitinib, although at a lesser extent. Keywords: Metabonomic, Sunitinib, hypothyroidism
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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 | 0.001 |
| 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".