Hsp90 and histone deactylase inhibitor have synergistic activity against synovial sarcoma.
Pourquoi ce travail est dans la base
Une base qui oublie comment elle a trouvé un travail ne peut pas être vérifiée. Voici les voies qui ont admis celui-ci.
Notice bibliographique
Résumé
B50 Clinically-applicable Hsp90 and histone deacetylase inhibitors have independently been shown to suppress growth and induce apoptosis in synovial sarcoma; this study tests the hypothesis that such agents may be synergistic, which would permit increased efficacy while reducing dose and minimizing potential side effects. Synovial sarcoma is an aggressive soft tissue malignancy of unknown cellular origin, which typically affects young adults and often proves fatal. The chromosomal translocation t(X;18)(p11.2;q11.2) resulting in the fusion oncoprotein SYT-SSX is characteristic of this disease, but its function in oncogenesis is unclear. Synovial sarcoma exhibits an undifferentiated mesenchymal phenotype that suggests its malignant transformation involves dysfunctional cellular differentiation. The Hsp90 inhibitor 17AAG is being tested in clinical trials in a variety of cancers including leukemias, lymphomas, and sarcomas. Histone deacetylase inhibitors (including MS-275) are also currently involved in clinical trials of several cancers including leukemias and lymphomas and are considered to be promising new therapies for a wide range of cancers. Recently, we (Terry J et al. Clin Cancer Res 2005;11:5641) and others (Ito T et al. Cancer Lett 2005;224:311) have found that both 17AAG and histone deacetylase inhibitors, as single agents, are successful in arresting growth of synovial sarcoma in vitro and slowing growth in xenografts. We therefore tested combinations of 17AAG with the histone deacetylase inhibitor MS-275 by MTT proliferation assays and by Annexin V flow cytometry apoptosis assay, using established synovial sarcoma cell line models. Synergism was assessed by the median-effect principle of Chou and Talalay. As single agents, the IC50 for 17AAG is 2.1 uM and for MS275 is 4.5 uM at 24 hours in these assays. In synovial sarcoma cell line SYO-1, 50% reduction in MTT absorbance at 24 hours was achieved by a combination of 0.1 uM 17AAG with 0.25 uM MS-275. This result is nine times more effective than if the drugs were simply additive. Synergistic effects were still present at later assay time points, and in the synovial sarcoma cell line Fuji. These results show, for the first time, that 17AAG and histone deacetylase inhibitors are synergistic against synovial sarcoma in vitro and suggest that low dose combination therapies may be effective against this disease.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,002 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle