Abstract 1398: Using zebrafish xenotransplantation to study the role of Y-Box binding protein (YB-1) in the metastasis of Ewing family tumors
Notice bibliographique
Résumé
Abstract Sarcomas are malignant cancers of soft tissue or bone predominantly affecting children and adolescents. The most common subtypes are osteosarcoma and Ewing family tumours (EFTs). The most unfavorable prognostic factor is the presence of metastases, which accounts for 9 out of 10 sarcoma cancer deaths. Identifying factors and/or drugs that have an impact on metastatic spread have tremendous potential to affect outcome by reducing disease burden to the primary site, which can be more effectively treated by surgery and radiation. Pertinent animal models are critical for translating in vitro findings to clinical trials. Xenotransplantation of human cancer cells into transparent zebrafish embryos provides a novel in vivo platform for visualizing tumor micro-environment interactions contributing to sarcoma proliferation and spread in real time, which is not easily provided by other animal models. We recently demonstrated the effectiveness of the zebrafish xenotransplantation model for the study of specific drug-tumor interactions for both chronic myelogenous leukemia and acute promyelocytic leukemia and used a rapid and novel ex-vivo proliferation assay to quantify therapeutic responses (Corkery et al, BJH 2011). We have now applied this technology to EFTs. Human EFT TC-32 cells were fluorescently labeled with CmDiI, and microinjected into the yolk sac of two day old casper embryos, a double pigment mutant that prevents any auto-fluorescence that might interfere with image quality. EFT cells successfully engrafted, survived and proliferated over 96 hours post-injection (hpi). Migration of cells from the yolk sac to the tail occurred between 48 and 144 hpi with evidence of vascular extravasation and tissue infiltration. Y-box binding protein 1 (YB-1) is implicated in the metastatic spread of epithelial cancers due to its key role in promoting an epithelial-to-mesenchymal transition (EMT). In contrast to parental TC-32 cells, xenografted YB-1 knockdown (KD) TC-32 cells showed absent or significantly delayed migration, suggesting that YB-1 also regulates this process in zebrafish xenografts. Moreover, using transgenic fli-EGFP casper embryos that display fluorescent vasculature, we saw evidence of vascular recruitment into the tumor mass in WT TC-32 cells but not in YB-1 KD, potentially implicating angiogenesis as a mechanism that contributes to tumor spread in YB-1 expressing sarcomas. Exposure of TC-32 xenografted embryos to 5-40 Gy of ionizing radiation effectively reduced cell proliferation in a dose-dependent manner. These studies highlight the utility of the zebrafish xenograft model to elucidate the mechanisms underlying the metastatic behavior of EFTs and position this system as an in vivo tool for drug discovery to identify novel anti-proliferative and anti-metastatic agents to improve outcome in this disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1398. doi:1538-7445.AM2012-1398
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 | 0,004 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 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 ».