Regulation of growth of renal clear cell carcinoma by peroxisome proliferator-activated receptor gamma
Notice bibliographique
Résumé
B67 Renal Clear Cell Carcinoma (RCC) is the tenth most prevalent cancer , accounting for 80% of all renal cancers. Recent results of a 15.3 year epidemiological study indicate that a diet of fatty fish offers significant protection against RCC, results which were attributed to omega-3 fatty acids. The question arises as to the molecular mechanisms by which such omega-3 fatty acids exert their protective effect. One possible mechanism is through the activation of Peroxisome Proliferator-Activated Receptors (PPARS) by omega-3 fatty acids, which presumably is altered during the process of tumorigenesis. In order to examine this hypothesis, normal renal proximal tubule cells have initially been examined with regards to their growth responses to PPAR agonists (the RCC is of renal proximal tubule origin). Towards these ends the effects of PPAR alpha and PPAR gamma agonists on the growth of a well-characterized primary renal proximal tubule cell culture system have been examined. The primary cultures were initiated from purified rabbit renal proximal tubules in serum free medium supplemented with 5 microgram/ ml bovine insulin, 5 microgram/ml human transferrin and 5 x 10-8 M hydrocortisone. Fibrate drugs and thiazolidinediones (TZDs) have been identified which have a high affinity for PPAR alpha and PPAR gamma, respectively. The effects of the TZD drug troglitazone on the growth of primary proximal tubule cells were examined over a concentration range between 10-7 and 10-4 M. After a 7 day incubation period, cells were removed from culture dishes by trypsinization, and counted in a Coulter Counter. The results of 3 independent studies indicated that troglitazone caused a 4-fold increase in cell number over a concentration range of 10-6 to 5 x 10-6 M. A physiologic PPAR gamma agonist, Prostaglandin J2 (PGJ2), was also growth stimulatory, albeit to a lesser extent than troglitazone. Both PPAR alpha and PPAR gamma are expressed in the renal proximal tubule. However, fenofibrate, a PPAR alpha agonist, had no significant affect on renal proximal tubule cell growth over a concentration range of 10-7 to10-4 M. Unlike the results that we have obtained with our normal renal proximal tubule cells, several recent studies have indicated that troglitazone, and other TZDs (PPAR gamma agonists) induce growth arrest and apoptosis in RCC, as well as other urological cancers. Presumably, PPAR gamma signaling is altered in RCC. Indeed PPAR gamma is included amongst the proteins that are up-regulated in RCCs as a consequence of mutations in the von Hippel-Lindau suppressor gene (VHL). Thus, omega-3 fatty acids may act to prevent the progression of the tumor stem cells which have arisen as a result of such mutations in the VHL gene. Alternatively, omega-3 fatty acids may act to prevent metabolic processes necessary for the emergence of RCC cells, with their distinctive lipid droplets.
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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) | 0,002 | 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 ».