Abstract 5313: The potential role of cellular iron in head and neck squamous cell carcinoma.
Notice bibliographique
Résumé
Abstract Introduction. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Half of the patients present with advanced disease, which despite aggressive treatments, achieves five-year survival rates of only 50%, underscoring a need to better understand the biology of this disease. One approach would be to examine the role of cellular iron in HNSCC. We are interested in the role of iron as a result of: (1) A previous study in our lab in which uroporphyrinogen decarboxylase was identified as a radiosensitizing target for HNSCC. The radiosentization was due to alterations in iron homeostasis which elevated reactive oxygen species (ROS) and enhance tumor oxidative stress and cytotoxicity. (2) The requirement of iron in a rate limiting step with ribonucleotide reductase for DNA synthesis, and hence cell proliferation. (3) The deregulation of iron in many cancers. Experimental design. A list of proteins involved in iron homeostasis was generate from the literature and evaluated using qRT-PCR in 3 HNSCC cells (FaDu, UTSCC 42a, UTSCC 8) compare to a Normal Oral Epithelial (NOE) cell line. The most highly over expressed iron protein across all cell lines compared to the NOE was hemochromatosis (HFE), thus was selected for further evaluation. Knockdown of HFE was achieved using a siRNA based approach and cellular effects were determined using MTS, clonogenic, BRDU and flow cytometry assays with or without 4 Gy of radiation. Iron rescue experiments where preformed using Ferric ammonium citrate (FACs). Iron chelation was accomplished in HNSCC cells lines using ciclopirox olamine (CPX), a clinical approved iron chelating chemotherapeutic. Results. HFE was selected for further evaluation based on the expression in HNSCC cell lines versus the NOE cell line. Mutations in HFE are linked to the genetic condition hemochromatosis, which is characterized by elevated hepcidin levels and iron accumulation in peripheral tissues. Cell proliferation assays (MTS, clonogenic, BRDU assay) after HFE knockdown with or without RT in HNSCC cells demonstrated a significant decrease in proliferation across all cancer cells with negligible effects on NOE cells. Furthermore, we observed a significant decrease in the Labile iron pool and cellular ROS levels, following HFE knockdown. Re-introduction of iron into the cell after HFE knockdown rescued our phenotype, suggesting that this process is indeed mediated by cellular iron levels. Next, we treated HNSCC cell lines CPX and observed a significant decrease in cell viability compared to control treated cells. Conclusion. HFE appears to be an important protein in controlling cellular iron. HFE knockdown resulted in a reduction in cellular iron which decreases the amount of iron available for DNA synthesis and hence cell proliferation. Therefore, elevated cellular iron appears to be an important factor for the progression of HNSCC, thus iron chelation strategies may valuable in the context of this disease. Citation Format: Michelle Lenarduzzi, Angela Hui, Winnie Yue, Justin Williams, Fei Fei Liu. The potential role of cellular iron in head and neck squamous cell carcinoma. [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 5313. doi:10.1158/1538-7445.AM2013-5313
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 ».