Altered phosphorylation of topoisomerase I following overexpression in an ovarian cancer cell line
Bibliographic record
Abstract
There is a growing interest regarding the use of camptothecins (CPTs) for the management of ovarian cancer. Since topoisomerase I has been established as a prime target of these drugs in other experimental models, it was important to determine whether sensitivity to CPTs in ovarian cancer cells is also correlated with the cellular level of this enzyme. Despite the 7-fold increase in topoisomerase expression achieved by adenovirus-mediated expression, the sensitivity to a CPT derivative (topotecan), was not improved compared with control cells harboring an endogenous level of the enzyme. This observation is in accordance with the similar level of topoisomerase I activity found in control and overexpressing cells and suggests that these cells may efficiently regulate the enzyme activity. Indeed, topoisomerase I overexpressing cells are characterized by a lack of alkaline phosphatase sensitivity and elimination of the hyperphosphorylated form of the protein. Taken together, these observations strongly suggest that an alteration in the phosphorylation state of topoisomerase I could limit its activity and prevent improvement of CPT response in ovarian cancer cells. In addition, a limited extent of topoisomerase I phosphorylating activity was found in nuclear extract of OVCAR-3 cells. Hence, providing enhancement in topoisomerase I expression may not result in improvement of CPT response in ovarian cancer cells because of an efficient control of the phosphorylation state of the enzyme.
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".