Effect of depsipeptide (NSC 630176), a histone deacetylase inhibitor, on human synovial sarcoma <i>in vitro</i>
Bibliographic record
Abstract
9039 Background: Synovial sarcoma is the fourth most common malignant soft tissue tumor of young adults. Its characteristic t(X;18)(p11.2;q11.2) leads to the production of an SYT-SSX fusion protein. Gene expression profiling studies and postulated functions of SYT-SSX both suggest altered chromatin structure is a central change in synovial sarcoma. Because chromatin structure is dependent on histone acetylation and deacetylation, the effects of depsipeptide (NSC 630176), a clinically applicable histone deacetylase inhibitor, was examined in vitro on human synovial sarcoma cell lines grown as monolayers and spheroids. Methods: Cytotoxic effects of depsipeptide (1, 10, 100, 1000 ng/ml) on SYO-1 and Fuji synovial sarcoma cells were measured by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay; results were compared against normal fibroblasts and various cancer cell lines. Apoptotic analyses by flow cytometry were subsequently performed for both monolayer and 3-dimensional synovial sarcoma cell culture systems. Results: Dramatic, dose-dependent cell death induced by depsipeptide was observed in both SYO-1 and Fuji cells at concentrations as low as 1 ng/ml, within 24 hours. Similar cytotoxicity was not observed in lung and breast carcinoma cell lines until 10 ng/ml and/or at later time-points, while normal fibroblasts, myeloma, and prostate carcinoma cell lines were much more resistant to drug treatment. The apoptotic population of monolayer SYO-1 and Fuji cells time-dependently increased to 83.1% and 85.2%, respectively, at 1 ng/ml following 72 hours. Three-dimensional spheroid cultures, intrinsically resistant to chemotherapy, also demonstrated effective synovial sarcoma cell death by depsipeptide at ng/ml concentrations. Conclusion: The molecular biology of synovial sarcoma suggests it may be sensitive to chromatin remodeling agents. The histone deacetylase inhibitor depsipeptide causes apoptosis-mediated cell death in human synovial sarcoma monolayer and spheroidal cell lines at very low, clinically-achievable concentrations. No significant financial relationships to disclose.
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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 | 0.000 |
| 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".