Abstract 5261: Irinophore C, a liposomal formulation of irinotecan, has anti-vascular effects in primary tumors of colorectal cancer grown orthotopically in mice
Notice bibliographique
Résumé
Abstract Introduction: Colorectal cancer accounts for ∼10% of cancer deaths in North America. Our group has developed a series of primary tumors from human colorectal cancer tissue obtained during surgery. These tumors are passaged orthotopically in mice and maintain the complexity and heterogeneity of the original patient sample. We have used these tumors to examine the cytotoxic and anti-vascular effects of Irinophore CTM, a liposomal form of irinotecan, which is more efficacious and less toxic than the parent drug. Materials and Methods: Primary tumor tissues from colorectal cancer patients, were validated by a reference pathologist and implanted subcutaneously in SCID mice. Tumors that grew successfully were then passaged orthotopically on the ascending colon of new mice. When these tumors reached ∼200mm3, groups of mice were treated with saline, irinotecan (50mg/kg), or IrinophoreCTM (25mg/kg) once a week for 6 weeks. Separate groups of tumors, A, B and C were harvested on days 3, 21 and 42 after treatment started, respectively. Magnetic resonance imaging (MRI) was used to assess tumor perfusion in mice from group B. Treatment effects on tumor metabolism were assessed with 18F -fluorodeoxyglucose and positron emission tomography (FDG-PET) for groups A and C mice. Immunofluorescence staining was carried out on tumors from all treatment groups to determine levels of cell proliferation, apoptosis, hypoxia, and vessel density. Results: 4 of 14 samples were successfully propagated and maintain their original morphology. Irinophore CTM treatment reduced tumor volume by 54% to 92% compared to the untreated controls depending on the tumor line. No toxic effects were seen with Irinophore CTM. The aggregate data for cell proliferation (Ki67), necrosis (H&E) and cell death (TUNEL) indicate that Irinophore CTM has sustained cytotoxic activity compared to the free drug. Immunostaining data show irinotecan treatment did not change blood vessel density in the tumors; however, Irinophore CTM treatment did reduce vascular density in the tumors. The volume transfer coefficient, Ktrans, derived from MRI, decreased when tumors were treated with irinotecan, but increased with Irinophore CTM treatment. Differences in the metabolic activity of the tumors were also seen. Conclusion: Orthotopic models of colorectal cancer propagated from patient tumors were successfully developed. These models retain the characteristics of the original patient sample and are a good alternative to xenograft models grown from immortalized cell-lines. The anti-tumor activity of Irinophore CTM at lower doses is greater than irinotecan's, and with fewer side effects. Treatment with Irinophore CTM also reduces tumor metabolism and appears to improve vascular function. The data imply that Irinophore CTM has sustained anti-tumor activity and multiple mechanisms of action compared to irinotecan. 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 5261. doi:1538-7445.AM2012-5261
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 | 0,001 | 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 ».