Abstract PO-057: Systemic delivery of miR-27a* using ultrasound-targeted microbubble cavitation causes tumor regression
Notice bibliographique
Résumé
Abstract Benefits from treatment with antibodies targeting the overexpression of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma (HNSCC) are observed primarily in combination with radiation therapy; anti-EGFR monotherapy results in less than 10% disease response. Despite extensive biological justification for EGFR inhibitors, marginal clinical benefit has been observed in broad populations. MicroRNAs (miRs) are short, endogenous, noncoding RNA molecules (19-22 nucleotides) that bind to target mRNAs, causing post-transcriptional RNA interference. Unlike siRNAs, which target a single gene, miRs have evolved to simultaneously target multiple proteins, making them attractive therapeutic candidates. Our previous studies showed that miR-27a* is repressed in HNSCC, and miR-27a* levels correlate with survival. We identified multiple miR-27a* targets in the PI3K-AKT1-mTOR pathway, the most commonly overexpressed mitogenic pathway in HNSCC, including EGFR, AKT1, and mTOR. Ectopic expression of miR-27a* inhibits tumor growth in both in vitro and in vivo HNSCC models, suggesting miR-27a* as a potential therapeutic intervention. However, substantial challenges exist in delivery of miRs to tumors. In the current study, we used an image-guided theranostic platform to systemically deliver miR-27a* to tumors. SCCVII-derived xenografts in immunocompetent C3H/HeJ mice were treated with miR-27a* or control miR mimics (miR-C). Therapeutic ultrasound was delivered using a single-element immersion transducer oriented directly over the tumor site, following continuous infusion of microbubbles loaded with 10 µg miR-27a* or miR-C into the jugular vein. Successful destruction and replenishment of microbubbles in the tumor area was confirmed by simultaneous contrast-specific ultrasound perfusion imaging with a clinical ultrasound imaging system. Using miRNAScope, an in situ hybridization-based method, we were able to visualize ultrasound-targeted microbubble cavitation (UTMC)-mediated delivery and spatial distribution of miR-27a* to the tumor cells. We found that UTMC delivery of miR-27a* lowered protein expression of miR-27a* targets (EGFR, AKT1, mTOR, NUP62, and ΔNP63α) compared with UTMC-delivered miR-C or intravenous miR-27a* treated mice at 48 hours after treatment. We also found that UTMC delivery of miR-27a* resulted in a significant reduction in tumor volume compared with both UTMC-delivered miR-C and intravenously delivered miR-27a* after 2 weeks (n=6 all groups). The potential therapeutic effects of miR-27a* were confirmed by its observed effect in lowering miR-27a* target levels and a significant inhibition of tumor growth. In conclusion, these observations clearly show that i) UTMC is an effective systemic miR delivery platform with the ability to concentrate miR delivery to the tumor site, and ii) miR-27a* is a potentially effective treatment for HNSCC. Citation Format: Nikhil S. Chari, Cheng Chen, Thiruganesh Ramasamy, Xucai Chen, Wei Lu, Khaja B. Khan, Lorena I. Gomez, Luisa M. Solis, Flordeliza S. Villanueva, Stephen Y. Lai. Systemic delivery of miR-27a* using ultrasound-targeted microbubble cavitation causes tumor regression [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-057.
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) | 0,002 | 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 ».