Abstract 479: Targeting tumor initiating cells inhibits tumor growth and serial transplantation ability in soft-tissue sarcomas
Notice bibliographique
Résumé
Abstract Tumors contain heterogeneous cell populations. There is a subpopulation of cells enriched for tumor initiating potential in sarcomas, which excludes Hoechst dye, and resides in the “side population” when subjected to flow cytometry (SP cells). These cells possess multi-potent differentiation potential, and as such they behave as “cancer stem cells” (CSCs), while the remainder of tumor cells act as “transient amplifying” cells. Because traditional cancer therapies may not target these tumor initiating cells, the persistence of SP cells could be responsible for relapse or a failed response to therapy. To detect signaling pathways that are differentially regulated in SP cells versus the remainder (non-SP) of the cells, we used gene profiling by microarray to compare their differences. RNA expressions were compared between these two cell populations from six malignant fibrous histiocytoma (MFH) samples using microarray. Differentially regulated genes were then analyzed by compiling a list of genes that showed a fold change greater than 1.25 in at least five of the six samples all in the same direction, and identifying if the list is enriched for genes involved in common molecular pathways, using Genespring® analysis tool. Two of the differentially regulated pathways detected were the Hedgehog signaling pathway and the Notch signaling pathway. Differential target gene expression for both pathways was verified using quantitative PCR. Triparanol (an agent that inhibits hedgehog signaling) and DAPT (an agent that inhibits Notch signaling) were used to treat eight primary MFH xenografts established in NOD-SCID mice. The xenografts produced visible tumors six weeks after subcutaneous transplantation, after which the mice were treated with one of the agents or a carrier as a control. At the end of the treatment, the tumors were harvested; their growth and SP% were assessed and compared; and the cells harvested from the treated xenografts were again implanted into mice to study the rate of re-growth upon secondary transplantation. Both triparanol and the Notch blocker DAPT treatment suppressed these pathways in tumor cells, depleted the abundance of SP cells, and reduced tumour growth. Intriguingly, treatment substantially inhibited the tumour-initiating potential of the treated sarcoma cells upon secondary transplantation. The data provides support that SP cells act as tumour initiating cells in sarcomas and shows that targeting the SP (in this case by targeting the Hh and Notch pathways) is an enticing approach for sarcoma therapy. 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 479. doi:10.1158/1538-7445.AM2011-479
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) | 0,003 | 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 ».