Abstract 1716: Mechanisms of resistance in carboplatin, docetaxel and dual drug resistant ovarian cancer cell lines
Notice bibliographique
Résumé
Abstract Carboplatin and docetaxel are two standard chemotherapeutics used to treat ovarian cancer. Patients often exhibit resistance to single agent therapy, and dual agent therapy was developed to overcome this resistance. However, resistance still commonly occurs in dual agent therapy. It is known that specific changes in gene expression occur in single agent resistance, but it is not known whether resistance to combined chemotherapy involves novel gene expression changes or if resistance is only the sum of changes seen in single agent resistant cells. Using the chemotherapy-naïve A2780 ovarian cancer cell line, we have generated three resistant cell lines including carboplatin and docetaxel single agent resistant lines (A2780CBN, and A2780DXL respectively), and a carboplatin/docetaxel dual resistant line (A2780CBNDXL) by exposing A2780 cells to increasing concentrations of drug until a dose is reached where resistance could no longer be developed. The concentration of drug at which 50% of cells die (IC50) was measured for reach resistant cell line using a clonogenic assay. The IC50 of A2780CBN is 8×10−5 M, 13-fold more resistant than the parent line. The IC50 of A2780DXL is 3×10−7 M, 5000-fold more resistant than the parent line. The IC50 of A2780CBNDXL is 8×10−6 M for carboplatin and 8×10−9 M for docetaxel. Changes in gene expression associated with the development of resistance in each cell line were identified by microarray analysis on Agilent 4×44k total human genome arrays. In the A2780CBN line there were a total of 1209 significant changes in gene expression, in the A2780DXL line there were 955 changes, and in the A2780CBNDXL line there were 1336 changes. The majority of changes in each cell line (70%) were unique, indicating that novel changes in gene expression occur in the dual line. A Functional Interaction Network-based analysis was conducted on the microarray data identify important gene clusters acting in the drug resistant A2780 ovarian cancer cell lines. Ten major clusters were found in the A2780CBN line, 8 clusters in the A2780DXL line and 10 clusters in the A2780CBNDXL line. Although similar clusters occurred among the lines, the genes in them were different and several unique clusters occurred in the dual line. Functional enrichment analysis will be done for every cluster and the most significant pathways will be taken into further consideration for validation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1716. doi:10.1158/1538-7445.AM2011-1716
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.
Comment cette classification a été obtenuedéplier
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 | 0,000 | 0,000 |
| 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 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| 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 découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».