Abstract 3080: Y-box binding protein 1 is crucial in acquiring drug resistance in advanced renal cell carcinoma
Notice bibliographique
Résumé
Abstract Objective: Investigating the role of Y-box binding protein 1 (YB1) in drug resistant advanced kidney cancer. Background: Renal cell carcinoma (RCC) is the 6th most common malignancy with approximately 1,800 deaths in 2015 and 2.3% annual increase in Canada. Despite the partial or total surgical removal of kidney in patients with localized RCC, metastatic patients are treated with tyrosine kinase inhibitors (TKIs) in a purely palliative approach. However, TKI-resistance (Sunitinib) is developed after a median time of 10-14 months. Therefore, identifying the factor(s) responsible for TKI-resistance development and disease advancement in RCC is imperative. It is now widely recognized that evolutionarily conserved Y-box binding protein 1 (YB1) is essential for cell growth and survival. Upregulation of YB1 in numerous cancer types was found to be positively correlated with tumor growth, metastasis and drug-resistance development. YB1 is also involved in intercellular communication through its secretion in the tumor microenvironment by cell-surface transporters, ABC-transporters. Summary of the data: Endothelial cells (HUVEC) were co-cultured with Caki-1DC (Sunitinib-resistant, developed in our lab) and Caki-1WT (Sunitinib-sensitive) RCC cell-lines, and increased migration of HUVEC was observed with Caki-1DC compared to Caki-1WT. A drastic increase in YB1 and its downstream target ABCB1 in Caki-1DC compared to Caki-1WT cells was also detected. Consistent with previous reports, we observed granular structures in the Caki-1DC cells that support potential secretion of YB1 into the tumor microenvironment. Moreover, blocking ABCB1 reverted the Caki-1DC cells to being drug-sensitive. Experimental procedures: Caki-1WT and Caki-1DC were co-cultured with HUVEC cells followed by scratch assay to test for HUVEC cell migration and associated secretory factors. Western blot and qPCR were used to determine the protein and mRNA levels respectively between the two cell-lines. Immuno-histochemical staining was carried out on the RCC tumors from Sunitinib-sensitive and resistant mouse models (developed in our animal facility). Granular structures were observed using immunofluorescence staining against YB1. Presto-blue was used for cell biomass assay following different drug treatments. Summary: The molecular function of YB1 in RCC and its potential in targeted therapy is not well understood. Therefore, understanding the function of YB1 in metastatic RCC and in drug-resistance development is of vital importance. Our data suggests that inhibition of YB1 may slow disease progression and, possibly, revert the drug resistance mechanism. The results from this study have the potential to introduce YB1 inhibitors in conventional RCC chemotherapy, alone or in combination, to improve survival in advanced kidney cancer patients. Citation Format: Ninadh M. D'Costa, Peter Raven, Zheng Tan, Werner Struss, Sebastian Frees, Claudia Chavez-Munoz, Alan I. So. Y-box binding protein 1 is crucial in acquiring drug resistance in advanced renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3080. doi:10.1158/1538-7445.AM2017-3080
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) | 0,000 | 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) | 0,006 | 0,002 |
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 ».