Abstract C210: Microregional distribution and activity of camptothecins in tumor xenografts.
Notice bibliographique
Résumé
Abstract Background: The tumor microenvironment plays an important role in determining the activity of many anticancer drugs and one critically important factor that has recently garnered considerable interest is the micro-regional distribution of anticancer drugs within tumors. One of the key issues being whether chemotherapy drugs reach all the cells within a tumor at concentrations high and long enough to exert a therapeutic effect. Irinotecan and topotecan are two camptothecin analogues with differing pharmacological and physicochemical properties, both exhibit clinical activity though are not curative. In this study the micro-regional distribution of the two analogues was compared to their pattern of activity with tumor cryosections. Methods: Using whole tissue section mapping and multiplexed immunostaining techniques irinotecan and topotecan fluorescence was detected in relation to tumor vasculature in cryosections from HCT116 xenografts 1, 2, 4, 8 & 24 hours following their administration. The tissue sections were subsequently stained to map drug activity via apoptosis and proliferation status at early (1–24 hours) and late (1–14 days) times after treatment. Results: Topotecan exhibited a faster and more uniform tissue distribution than irinotecan but experienced significant wash-out within the first 2 hours following treatment. Irinotecan exhibited a larger concentration gradient in relation to tumor blood vessels but appeared to benefit from a longer retention within the tissue, with significant exposure occurring out to 8–24 hours following treatment. Interestingly, irinotecan did not appear to permeate equally from all vessels within the tumors. Some areas of the tumors received much higher exposure than others. At 50 mg/kg irinotecan and 10 mg/kg topotecan, both agents were able to exert a uniform block of cycling tumor cells within 4 hours of treatment but by 24 hours tumor proliferation status had returned to near normal levels indicating neither drug was retained long enough to exert activity on cells that were out of cycle at time of treatment. Conclusions: Development of new camptothecin analogues might benefit from design strategies to increase tumor retention and uniformity in tissue distribution. While both irinotecan and topotecan were able to exert a significant and uniform cell cycle block within 4 hours of treatment in the HCT116 xenografts, due to their short retention proliferation was seen to recover by 24 hours. Irinotecan appeared to distribute less uniformly within the tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C210.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| 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) | 0,000 | 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 tête enseignante, 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 ».