Increase of therapeutic effects by treating melanoma with targeted combinations of c-myc antisense and doxorubicin.
Notice bibliographique
Résumé
C106 Patients with advanced or metastatic melanoma have a very poor prognosis, due to the resistance of melanoma cells to conventional chemotherapy. We previously reported that coated cationic liposomes (CCL) targeted with a monoclonal antibody against the disialoganglioside GD2 and containing c-myc antisense oligodeoxynucleotides (αGD2-CCL[c-myc-as]) resulted in selective inhibition of the proliferation of GD2-positive melanoma cells in vitro, while inducing apoptosis and partial tumor growth arrest in melanoma xenografts. Our aim in this work was to define the role of c-myc-asODN treatment in the susceptibility to doxorubicin (DXR) in human melanoma cells, both in vitro and in vivo. To determine chemosensitization of melanoma cells to DXR by c-myc antisense oligodeoxynucleotides (asODNs), human melanoma cells were incubated for 2 h with αGD2-CCL[c-myc-as] (10 μM asODN concentration). After washing, cells were then incubated with DXR (concentrations ranging from 0.061 μg/ml DXR to 250 μg/ml) and the inhibition of cell proliferation determined after 48 hours by the MTT assay. Annexin V-FITC and propidium iodide (PI) double staining were used to detect apoptotic and necrotic cells after treatments. For in vivo experiments, athymic mice were injected subcutaneously with the human melanoma cell, MZ2-MELand intravenously treated, every day for 3 days, with 3.5mg ODN/kg of αGD2-CCL[c-myc-as], untargeted liposomal DXR (SL[DXR]) or αGD2-targeted liposomal DXR (αGD2-SIL[DXR]) at 2 mg DXR/kg, or with a combination of the ODN and DXR formulations. Histological evaluation of cryopreserved tumor tissues was performed at 7 and 14 d from the end of treatment, using mAbs against the Ki-67 proliferation antigen, the endothelial marker CD31 and TUNEL for detecting apoptosis. In vitro cytotoxicity studies revealed that growth of melanoma cells was inhibited to a greater extent by αGD2-CCL[c-myc-as] than by the corresponding untargeted formulations or by free c-myc-as. Targeted c-myc-as sensitized cells to DXR, reducing the IC50 by approximately 10-fold. Scrambled ODNs had no effect on the IC50 of DXR. Compared to either treatment alone, combination of targeted c-myc-as and DXR resulted in earlier apoptosis and necrosis after 2 days of treatment. In vivo experiments revealed that liposomal formulations of c-myc-as and DXR, both targeted via GD2, led to the most pronounced delay in tumor growth when administered in a sequential manner. As a result, their combination translates into a statistically significant suppression of blood vessel density and an enhanced apoptosis, compared to all treatments given separately. Our data indicate the increasing cell sensitivity to DXR by targeted c-myc-asODNs as a promising basis for developing novel anti-tumor strategy against advanced melanoma. F.P. is a recipient of a Fondazione Italiana per la Lotta al Neuroblastoma fellowship.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, 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 ».