Abstract 2907: Novel liposomal compositions of PharmaGap's lead peptide: Effect on ovarian cancer cell proliferation and signaling pathways
Notice bibliographique
Résumé
Abstract Background: Liposomes, vesicular structures in the nano - micrometer range, have been widely studied as drug delivery vehicles. Liposomes can self-assemble in aqueous solutions and are normally comprised of lipids organized in concentric bilayers that enclose an internal aqueous volume, unique in their ability to accommodate a wide variety of therapeutic or diagnostic compounds. Novel liposomal compositions of peptide GAP-107B8, have recently been developed and their inhibitory effect on cell proliferation in cancer cell lines has been studied. Protein kinase B, Akt, has been implicated in certain cancer functions, including cell motility and invasion, hormone independence, chemotherapy and radiation resistance. Abnormalities in Akt are associated with certain breast, pancreatic, colorectal, gastric and ovarian cancers. The present work shows that an important mechanism of action for GAP-107B8 peptide formulations is through modification of protein kinase pathways. Objectives: 1) To optimize GAP-107B8 liposomal formulations, 2) To evaluate the efficacy of GAP-107B8 liposomal formulations towards inhibiting proliferation in ovarian cancer cell lines and 3) To gather information on the inhibitory mechanism of action in ovarian cancer cells. Methods: Optimization of the lipid components in the liposomes including lipid identity and ratio in relation to extent of peptide-liposome association was determined by IEC, liposome size and charge. Cell proliferation was measured in A2780cp and OCC-1 ovarian cancer cell lines with liposomal peptide formulations (24 and 72 hrs). Immunoblotting experiments were executed on cancer cell line lysates treated with peptide to explore inhibitory effects on signaling targets. Results: Peptide association ranged from 80-100% for liposomal formulations prepared with two lipid components in varying ratios (formulation 2A and 2B) as opposed to a single lipid component (formulation 1 - 30%). Treatment of ovarian cancer cells with liposomal formulations 2A, 2B and 3 showed significant inhibition on cell proliferation when compared to control groups. Densitometry results showed a 50% reduction in pAkt levels (relative to Akt levels) when ovarian cells were treated with peptide for 1 hour (similar inhibitory effect found after peptide treatment for 4, 8, 14 and 30 hours). Conclusions: A lipid based delivery system for GAP-107B8 peptide was developed in which lipid ratio played an important role for an enhanced peptide-associated liposomal formulation. Proliferation results indicate that administration of peptides in liposome formulations generally results in improved potency in a time dependent manner. All formulations exhibited greater potency after 72 hrs in comparison to earlier time points. GAP-107B8 was found to be a peptide-based inhibitor of protein kinase B (Akt) with a strong potential for anti-cancer properties. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2907. doi:1538-7445.AM2012-2907
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 | 0,000 |
| 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 ».