Abstract 566: Role of bone marrow derived cells in response to ionizing radiation in normal brain
Notice bibliographique
Résumé
Abstract Introduction: Radiation therapy (RTx) plays a critical role in treatment of malignant gliomas however the biological response to ionizing radiation (IR) in normal brain and brain tumors is poorly understood. We postulate that Bone Marrow Derived Progenitor Cells (BMDC) are involved in modulating radiation response in normal brain and brain tumor vasculature. Methods: Animal Models: Bone marrow of NOD/SCID mice were stably reconstituted with BM harvested from green-fluorescent protein transgenic mice. Intracranial (ic) xenografts were generated in intracranial window models (ICW) using U87 glioma cells stably expressing mCherry. RTx: Using locally designed x-ray micro-irradiator stereotactic radiation was delivered through ICW to normal brain or U87-mCherry ic-xenografts, treated with two fractionated regimens of 3×2Gy, 3×5Gy and single radiation doses of 2, 6, 8 and 15 Gy. RTx alone to normal brain was compared to RTx to U87-mCherry ic-xenografts and sham needle injection alone (15 mice each). In-vivo imaging: Two-photon laser capture microscopy was used to obtain high-resolution real-time in-vivo longitudinal images of the tumor cells, tumor vasculature and tracing of the circulating GFP+BM cells. Mice were imaged 1d,2d,3d,7d,10d,14d,21d & 30d following cell implantation or RTx. Histological Analysis: Mice were sacrificed using perfusion fixation and brains collected for correlative immunohistochemical and Immunofluorescent analysis. Results: In normal brain there is a dose dependent recruitment of BMDC to site of IR, in addition to a temporal response.BMDC is seen as early as 12hrs post IR and persists beyond 30 days, which is in contrast to needle injection alone where BMDC dissipate after 7 days. BMDC recruited to sites of IR in normal brain do not migrate outside of the radiation field and do not differentiate into other cell types, which is in striking contrast to glioma intracranial models, where tumor cells trigger a distinct differentiation of BMDC into macrophages, GFAP+astrocytes and monocytes that migrate beyond the irradiated zone. In both normal brain and brain tumor associated vasculature, following IR, BMDC integrates into the vasculature as pericytes and not endothelial cells. At higher radiation doses there is increased BMDC integration into both normal and tumor associated vessels. Conclusions: Our results are the first to demonstrate an early dose dependent recruitment of BMDC to site of IR in normal brain. BMDCs recruited to site of IR require a second signal, such as oncogenic signal from glioma cells, in order to differentiate to form other cell types such as GFAP+astrocytes, Macrophage+ and Monocyte+ cells. Increased integration of BMDC into the vasculature as perictyes following IR is suggestive of a protective role of BMDC. It is conceivable that the recruitment of BMDC to site of radiation in normal brain can be used towards a protective therapeutic strategy against adverse radiation effects. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 566. doi:10.1158/1538-7445.AM2011-566
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) | 0,004 | 0,002 |
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 ».