Growth inhibition of synovial sarcoma cells by curcumin
Bibliographic record
Abstract
646 Synovial sarcoma (SS) is a soft tissue malignancy for which no effective systemic therapy currently exists. It represents 7-10% of primary soft tissue malignancies and most typically arises in the extremities of young adults. The results of expression profiling studies by our group and others indicate that Wnt/β-catenin signaling pathway may be particularly important to the biology of SS. In addition, our group’s analysis of β-catenin using tissue microarrays has revealed nuclear accumulation of this protein in patient SS samples, a strong evidence for its activation. Interaction of β-catenin with Tcf4, and thus expression of its target genes, has been recently shown to be regulated by acetylation of β-catenin by p300. Therefore, inhibitors of the p300/ β-catenin pathway may represent a novel targeted therapy for this disease. We examined the cytotoxic effect of curcumin, a reported p300 inhibitor, in SS cell lines. Two SS cell lines, Syo1 and Fuji, were treated with 1 - 100 uM of curcumin for 24, 48 and 72 hours. The effect of curcumin on cell growth was measured by MTT assay and apoptosis was measured by flow cytometry using Annexin V. Doxorubicin was used as positive and vehicle (dimethyl sulfoxide) as negative control drugs. Normal fibroblasts were used as control cells. Dose and time dependent cytotoxicity was observed in both SS cell lines, with doses above 10 μM (Figure). Syo-1 cells were slightly more sensitive to curcumin than Fuji cells, with cell death matched to that of doxorubicin at 25 μM curcumin for Syo-1 cells and 50 μM curcumin for Fuji cells. Much less cytotoxicity was seen in normal human foreskin fibroblasts (30% viable cells vs. less than 10% in both SS cell lines after 72 hours treatment with 100 μM curcumin). The results of Annexin V assay indicated that the observed cell death after curcumin treatment occurred through apoptosis in a dose dependent manner. Expression profiling and tissue microarray analysis of SS indicates that Wnt/β-catenin pathway plays an important role in the development of this tumor, and curcumin, an inhibitor of p300 involved in acetylation of β-catenin, is a potent inhibitor of SS cell growth.
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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) | 0.002 | 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".