Abstract 3217: Mechanistic analysis of the ketogenic diet versus KetoCal® as adjuvant treatments for malignant glioma
Notice bibliographique
Résumé
Abstract Patients with malignant brain tumors have a median survival of approximately one year following diagnosis, regardless of currently available treatments which include surgery followed by radiation and chemotherapy. Improvement in the survival of brain cancer patients requires the design of new therapeutic modalities that take advantage of common phenotypes. One such phenotype is the metabolic dysregulation that is a hallmark of cancer cells. It has therefore been postulated that one approach to treating brain tumors may be by metabolic alteration such as that which occurs through the use of the ketogenic diet (KD). The KD is high-fat, low-carbohydrate diet that has been utilized for the non-pharmacologic treatment of refractory epilepsy. We and others have shown that this diet enhances survival in mouse models of malignant gliomas. There are varying formulations of the diet that alter the ratio of fats to carbohydrates & protein, and it is not clear whether any one is more effective than another. Bio-Serv F3666 (Frenchtown, NJ) is a rodent KD with a 6:1 ratio of fat:carbohydrate & protein. We have previously shown that ad libitum feeding of this diet significantly increased survival in albino C57BL/6 mice (NCI, Frederick, MD) stereotactically implanted with GL261-luc2 cells, a syngeneic bioluminescent mouse model of malignant glioma. Radiation in combination with KD was synergistic, and survival was significantly increased over either treatment alone. Ad libitum feeding of KetoCal® (KC; Nutricia North America, Gaithersburg, MD); a nutritionally complete, commercially available 4:1 (fat: carbohydrate & protein) ketogenic formula used for the treatment of pediatric epilepsy, also resulted in a significant increase in survival. However, the combination of radiation with KetoCal® caused the tumors to completely regress in 9 of 11 mice, and the tumors did not recur when these animals were switched back to standard rodent chow. The mechanism(s) by which the KD and KC exert their anti-tumor effects are not completely understood. We have begun to compare these 2 formulations to identify their anti-tumor effects. Animals on KC showed a more pronounced drop in blood glucose than those maintained on KD. Blood levels of α-hydroxybutyrate were significantly higher in animals fed KC than those in animals fed KD. Total AKT was reduced in tumor tissue from animals fed KC, but not in animals fed KD; however, phospho-AKT(Thr308) was reduced in tumor and non-tumor tissue from animals maintained on KD, but not those maintained on KC. Furthermore, tumor tissue from animals fed KD had a more pronounced decrease in insulin growth factor-1 than did tumor tissue from animals fed KC. These data suggest that the mechanisms leading to increased survival may be different in animals fed KC versus those fed KD. A greater understanding of the effects of different ketogenic formulations will allow for a more rational approach to its clinical use. 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 3217. doi:1538-7445.AM2012-3217
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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 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 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 ».