Abstract 4318: Biomarker evaluation during an image-guided intracranial murine glioma study of radiation and sunitinib
Notice bibliographique
Résumé
Abstract Introduction: Tumour angiogenesis, a hallmark of glioblastoma multiforme, serves as a potential therapeutic target. Sunitinib (SU) is a multi-targeted tyrosine kinase inhibitor with antiantiogenic activity that may enhance radiation (RT) effects. In preclinical studies using intracranial (IC) mouse tumour models, a major challenge is the ability to evaluate IC tumour size, growth and vascular changes over time. This study aims to use an image-guided experimental design to evaluate the effects of RT and/or SU in an IC murine glioma model using serial micro-MRI and urine biomarkers with corresponding pathology, tumour growth delay (TGD) and survival (OS)outcomes. Methods: U87 glioma cells were inoculated by IC injection in the right frontal lobe of 58 NOD SCID mice. Imaging was performed on a 7-Tesla Bruker BioSpec on day 7 post-injection (treatment D0), D3, 7, 10, 14, 17 and 21. Mice with visible tumours on D0 T2-weighted (T2-w) imaging were stratified by tumour size to treatments: (1) control (CTRL) - placebo (2) RT - RT + placebo (3) SU - oral gavage SU (4) RT + SU. RT 8 Gy was delivered in 1 fraction to the right hemi-brain on D1 under image-guidance. SU 0.8 mg or placebo was administered by oral gavage. Serial imaging/analysis included: (1) T2-w imaging (2) Quantitative T1 (3) DCE-MRI - initial area under the DCE curve at 60 seconds (iAUC60) (4) diffusion weighted imaging - apparent diffusion coefficient (ADC) (5) contrast-enhanced T1-w imaging (T1-gad). Expression of angiogenesis markers were measured in serial urine samples. Pathological evaluation included tumour size, cell density, vessel density/permeability and apoptosis. Results: Fifty-two mice with tumours were assigned to treatment arms such that mean tumour volume for each arm was 0.58 - 0.61mm3 (p>0.05) on D0. No mice expired with serial contrast-enhanced imaging. OS was significantly better with RT (p=0.008) and SU+RT (p=0<0.001) than CTRL, and SU+RT better than SU (p=0.018) and RT (p=0.05). Exponential tumour growth occurred in CTRLs but TGD was noted in all treatment arms until D14. Changes in iAUC60 showed trends/differences between treatment arms only at early timepoints: (1) RT - rise by D3 (2) SU - stable during SU (3) SU+RT - decrease of 30.1+6.8% by D3, maintained during SU. Baseline tumour ADC values were 8±5% above CL brain across all animals. Rise in ADC was greatest with RT and SU+RT (43±10%, 28±7%) than CTRL and SU (16±4%, 19±19%) at D10. Conclusion: This study demonstrates the potential utility of image-guidance to augment murine intracranial tumour studies of RT and AA therapy. Survival was improved with combined SU+RT. Promising early biomarkers of response identified to date include DCE at D3, and ADC at D10, warranting further investigation in a larger cohort. Further study of these markers may improve temporal characterization of vessel normalization and enable studies to optimize scheduling of antiangiogenic therapies with radiation. 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 4318.
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) | 0,001 | 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) | 0,001 | 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 ».