Abstract A031 Early metastatic dissemination in a MYCN-driven zebrafish model of high-risk neuroblastoma
Notice bibliographique
Résumé
Abstract Neuroblastoma (NB) is a highly metastatic tumor of the peripheral sympathetic nervous system and is responsible for 10% of childhood cancer deaths. MYCN amplification remains one of the most substantial prognostic factors of a poor patient outcome and is detected in 20% of all NB patients. Patients are designated as high-risk (HR) when greater than 18 months of age with metastatic disease or MYCN-amplified. The overall survival rates for HR patients remain below 50% even with intensive multi-modal treatment. Despite the central role of metastatic disease in HR-NB treatment failure, little is known about the mechanisms that control metastatic dissemination. MYCN_TT is an aggressive zebrafish model of HR-NB that highly expresses MYCN and has brightly EGFP-labeled tumor cells. A previous study from our lab shows that MYCN_TT zebrafish spontaneously metastasize with micro-metastasis detected at 6 weeks post-fertilization (wpf) and that a larger number of metastatic foci were observed with the overexpression of metabolic enzyme dihydrolipoamide S-succinyltransferase. The primary tumor originates in the interrenal gland adjacent to the head kidney. We collected MYCN_TT zebrafish at 3-, 3.5-, and 4-wpf, fixed them in paraformaldehyde, and then the fish were frozen. Samples were then serially sectioned on a cryostat, mounted on slides, and stained with DAPI. The slides were imaged on a wide field fluorescent scope. As MYCN_TT primary tumors begin to grow from cells within the interrenal gland at 3wpf, they are isolated from the kidney structures within the head kidney. By 4wpf, MYCT_TT primary tumors have more than doubled in size and have surrounded the renal corpuscle in 75% of fish. These renal corpuscles became abnormal: dilated, discontinuous lining of Bowman’s capsule, the vessles of the glomerulus have collapsed, and the Bowman’s space have been invaded by tumor cells interacting with the glomerular tuft. Additionally, disseminated tumor cells (DTC) were first identified at 4wpf at sites common for metastasis zebrafish models of NB (eyes, gills, spleen). DTC were only observed when the primary tumor in MYCN_TT zebrafish has surrounded the renal corpuscle. These results demonstrate that the glomerular tuft is the vascular source for hematogenous dissemination of MYCN_TT zebrafish. Our data also shows that metastatic dissemination is an early event in MYCN_TT tumorigenesis. The MYCN_TT zebrafish model will provide insight and new avenues of investigating the metastatic process in NB, such as, understanding the genetic differences between the primary tumor and metastasis; elucidating the factors that drive tumor invasion and determining the fates of DTC (e.g., dormancy). Citation Format: Kyle Woodward, Borum Ryu, Lauren Temple, Brian Tran, Perla Luna, Nicole Anderson. Early metastatic dissemination in a MYCN-driven zebrafish model of high-risk neuroblastoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A031.
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) | 0,000 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| 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 ».