Abstract 4680: Intracranial breast cancer brain metastases (BCBM) models - stereotactic vs. intracarotid inoculation
Notice bibliographique
Résumé
Abstract Breast cancer is the most prevalent cancer in women worldwide. 30% of breast cancer patients develops metastases at distant organs, with 10-20% of these patients developing brain metastases. The median survival time for patients with brain metastases is only 7.2 months and there is an urgent need for effective therapies. Development of novel therapies relies on good translational animal models. Subcutaneous tumors are technically easy and highly reproducible but lacks the natural tumor environment and the impact of the blood brain barrier. Breast cancer brain metastasis (BCBM) models are most often established by stereotactic intracranial inoculation. However, this leads to formation of single tumors and does not take the extravasation and seeding part of the metastatic cascade into account and resembles primary tumors to a larger extend. Intracarotid inoculation incorporates extravasation and seeding of micro metastases making it a better suited translational animal model for BCBM. A panel of intracranial BCBM was established through stereotactic and intracarotid inoculation of breast cancer cell lines with high survival and take rates (>85%). The panel included the ST941 PDX model, an estrogen receptor positive model harbouring the ESR1-Y537S mutation and exhibiting resistance to fulvestrant. The panel also included the triple negative breast cancer cell line MDA-MB-231 as well as HER2+ models. Tumor establishment and progression were evaluated using bioluminescence and magnetic resonance imaging (MRI). Whole brain and tumors were isolated, and paraffin embedded for histological evaluation of tumor establishment, invasiveness, and infiltration. Intracranial tumor establishment was evident early after inoculation using bioluminescence imaging and tumor growth was later confirmed by MRI. Tumor growth rate were dependent on inoculation method with rapid tumor growth observed with stereotactic inoculation. While stereotactic inoculation led to single tumor establishment with defined tumor borders, intracarotid inoculation led to micro seeding with multiple foci established throughout the brain. At early timepoints, the metastases consisted of <150 cells per metastases, but at later timepoints larger metastases were formed. Tumor infiltration was more diffused in brains with multiple metastases and the blood brain barrier integrity was different when comparing the models and inoculation methods. A panel of BCBM was successfully established using both stereotactic and intracarotid inoculation. While bioluminescence allowed the earliest tumor imaging, MRI provided additional information on tumor establishment such as location, numbers, and blood brain barrier permeability. The models showed varying tumor establishment, infiltration, and marker expression. The established panel can be used as a platform for testing novel anti-cancer therapies targeting BCBM. Citation Format: Sigrid Cold, Moritz Braig, Trine Bjoernbo Engel, Maria Zeiler Alfsen, Maria Nikoline Kristiansen, Lotte Kellemann Kristensen, Andreas Kjaer, Carsten Haagen Nielsen. Intracranial breast cancer brain metastases (BCBM) models - stereotactic vs. intracarotid inoculation. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4680.
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) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| 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 | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,001 |
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 ».