Abstract 1596: Evaluation of radiosensitizing effects of KSP inhibition in cancer cells.
Notice bibliographique
Résumé
Abstract Background: Several chemotherapeutic agents act as radiosensitizers, priming the cancer cells to the effects of ionizing radiation and resulting in increased tumor kill with radiotherapy. The combination of radiosensitizing chemotherapeutics and localized external beam radiation therapy is based on the scientific rationale derived from both preclinical and clinical observations of synergism between radiotherapy and chemotherapy. Recently, many kinesin spindle protein (KSP) inhibitors have undergone preclinical and clinical investigation as anticancer agents. The mitotic kinesin is an essential mitotic enzyme with no role outside of mitosis. KSP is essential for separation of spindle poles during mitosis; therefore its inhibition causes mitotic arrest and subsequent cell death. Amongst the various KSP inhibitors, SB-743921 is a highly potent second generation KSP inhibitor that has shown activity in a broad spectrum of tumor models and is now being investigated in clinical trials. We sought to investigate the radiosensitizing properties of SB-743921 in various cell lines in order to investigate its potential as a radiosensitizer for enhancing treatment efficacy in multiple cancers. Materials & Methods: We first assessed the inhibitory activity of SB-743921 in multiple cell models (hepatocellular carcinoma, colorectal cancer, breast cancer, pancreatic cancer). The half-maximal inhibitory concentrations (IC50) were determined by carrying out cell viability assays in each of these cell lines. Cancer cells were exposed to various concentrations of SB-743921 in growth medium for 72 hrs before cell viability was determined by colorimetric estimation of metabolic activity using XTT assay. Further, we evaluated the radiosensitizing effect of SB-743921 on hepatocellular carcinoma and colorectal cancer cells by performing clonogenic assays. Cells were first treated with SB-743921 for 24 hours at their respective IC50 values, followed by irradiation with 2-8 Gy doses. Post-treatment, the cells were plated at clonal density and incubated in growth medium for 10-14 days. Cells were fixed and stained, and colonies with 50 cells or more were counted. Results: The IC50 values of 4 cancer cell lines were between 0.5-2.5 nM. The results from the clonogenic assays indicate radiosensitization effect in the heptatocellular carcinoma cell line, whereas in the colorectal cancer cell line, radiosensitization was not observed. Conclusion and Future studies: From our results, it can be concluded that KSP inhibition with SB-743921 radiosensitizes some types of cancer, but not all. More cancer cell lines are currently being evaluated to demonstrate a relationship between cancer type and the radiosensitization effect by KSP inhibition. In future, in vivo chemoradiation experiments in mice will be performed in multiple cancer models to further assess the radiosensitization effect by KSP inhibition. Citation Format: Ripen Misri, Nelson Wong, Mohamed Khan. Evaluation of radiosensitizing effects of KSP inhibition in cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1596. doi:10.1158/1538-7445.AM2013-1596
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| 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 | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,001 |
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 source (Gemma direct ou Codex distillé), 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 ».