Abstract 3661: Vascular changes and potentiating secondary drug delivery in colorectal cancer with Irinophore C
Notice bibliographique
Résumé
Abstract Introduction: Colorectal cancer is the third most common cancer in the world. The predominant chemotherapeutic treatment in CRC is a combination of 5-fluorouracil (5-FU) and irinotecan (CPT-11). However, the combination is limited by toxicity and resistance. We now report on the effects of 5-FU in combination with a liposomal formulation of CPT-11, Irinophore C, that is more efficacious and less toxic than free CPT-11. Materials and Methods: 5-FU was used singly and in combination with Irinophore C in a subcutaneous model of colorectal cancer, HT-29, to assess therapeutic efficacy and toxic effects. 5-FU and Irinophore C (40mg/kg) were injected intravenously on a Q7Dx3 schedule, and tumor growth delay was measured. In a subsequent study, a single bolus injection of 14C-spiked 5-FU was delivered at different timepoints during Irinophore C (tritium-labeled) or saline treatment (Q7Dx3), and the accumulation of 5-FU in tumor tissue measured with scintigraphy. Tumors were also harvested and snap-frozen at early (days 1 - 7) and late (days 14 and 21) time points following Irinophore C treatment. Cryosections were subsequently examined for perfusion using the fluorescent dye Hoechst 33342, stained for apoptosis (TUNEL), CD31, CD105, Collagen IV and with H&E to examine changes in vascular function and tissue morphology. Results: Irinophore C significantly reduced tumour growth (p<0.001) with little or no toxicity compared to saline controls, 5-FU alone and free CPT-11 plus 5-FU. In some cases, tumour growth was completely abolished. When used in combination with 5-FU, there was a slight increase in growth delay. Treatment of the tumours with Irinophore C increased the accumulation of the active lactone form of the drug in the tumour, and also significantly increased the tissue accumulation of a single bolus injection of 5-FU after two (∼50% increase, p<0.001) and three weeks (∼66% increase, p<0.001). Following treatment with Irinophore C, the density of tumor tissue was decreased, and the vascular coverage was increased, leading to increased total perfusion. In addition, apoptotic activity was increased following 1 to 2 weeks of treatment with Irinophore C, compared to controls. Conclusions: Irinophore C is more efficacious, and less toxic, than free CPT-11. This novel formulation of CPT-11 appears to have a bimodal mechanism of action wherein both endothelial and cancer cells are targeted, and which may improve the delivery of a second drug. We further believe that the dose of Irinophore C used in the combination studies is with 5-FU is overly efficacious and masks the effects of 5-FU. Clinically, Irinophore C with its low toxicity and high efficacy could have advantages over the use of free CPT-11. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3661.
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) | 0,001 | 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 ».