Abstract 4915: High degree of G2/M arrest induced by Polo-like kinase 1 (PLK1) inhibition is associated with radiosensitization
Notice bibliographique
Résumé
Abstract Inhibition of polo-like kinase 1 (PLK1) seems to be a plausible avenue for sensitizing cancer cells to radiation. It has been demonstrated that normal cells tolerate PLK1 depletion well, when compared to cancer cells, suggesting a wide therapeutic index. This has been confirmed with our results from proliferation assays conducted with two primary human cell lines and various cancer cell lines. Recently, it has been shown that head-and-neck squamous cell carcinoma and medulloblastoma cells can be radiosensitized by PLK1 inhibition. Furthermore, PLK1 is involved in repair of DNA double-strand breaks. Together, these results suggest that PLK1 inhibition is a particularly attractive means of radiosensitization. To further investigate the radiosensitization property of PLK1 inhibition, clonogenic assays were carried out. Various cancer cell lines were treated with specific PLK1 inhibitor BI 2536 and subjected to various doses of ionizing radiation. The cancer cell lines were of breast, colorectal, and pancreatic origin. We found that some, but not all, cancer cells were radiosensitized by pre-treatment with BI 2536. Mutational statuses of p53 and KRAS were examined, but no relationship between the mutational statuses and radiosensitization by BI 2536 treatment was found. Since PLK1 inhibition causes G2/M arrest, which is the cell cycle phase that is known to be more sensitive to ionizing radiation, we assessed the percentage of cancer cells at G2/M phase when treated with or without BI 2536. Cells were treated with BI 2536 for 24 hrs before they were fixed, stained with propidium iodide, and analyzed with flow cytometry. The degree of G2/M arrest induction was assessed by G2/M induction index, as defined by % of G2/M cells before treatment / % of G2/M cells after treatment. We found that the G2/M induction indices were significantly higher with the cells that can be radiosensitized with PLK1 inhibition, when compared to those of the cells that cannot be radiosensitized. Therefore, we conclude that high G2/M induction index is predictive of radiosensitization with PLK1 inhibition. Future experiments of this project include determining the G2/M induction index threshold required for achieving radiosensitization and indentifying the molecular basis of such association. Citation Format: Nelson Wong, Mohamed Khan. High degree of G2/M arrest induced by Polo-like kinase 1 (PLK1) inhibition is associated with radiosensitization. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4915. doi:10.1158/1538-7445.AM2014-4915
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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) | 0,000 | 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 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 ».