Abstract C265: Significant <i>in vivo</i> activity of ENMD-2076, a novel multi-targeted kinase inhibitor, towards xenograft models of human hepatocellular carcinomas .
Notice bibliographique
Résumé
Abstract Background: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. It represents the third leading cause of cancer deaths worldwide, with over 500,000 people affected each year. The incidence of HCC is particularly high in China, accounting for more than 50% of the global incidences. The development of targeted anticancer agents effective against HCC for patients who do not tolerate, or have failed or relapsed from sorafenib treatment would meet a major unmet medical need. ENMD-2076 is an orally bioavailable small molecule inhibitor of Aurora A and angiogenic kinases including VEGFR 2 and FGFR 1 with pro-apoptotic, antiproliferative and angiogenic activities against a variety of human cancers. ENMD-2076 has been tested in multiple Phase I and II clinical trials, with partial responses (PR) and prolonged progression free survival (PFS) observed in multiple cancers including liver cancer. Objective: This in vivo study was designed to compare the efficacy of ENMD-2076 with that of standard of care agents including sorafenib, doxorubicin, and 5-FU in 3 different cell-line derived human HCC xenograft models. The tolerability and efficacy of combinations of ENMD-2076 with doxorubicin or 5-FU were also determined. Experimental Design: Three different human HCC cell lines, SMMC-7721, QGY-7703 and HepG 2 were used for establishing subcutaneous tumor xenograft models in nude mice. After tumors grew to more than 100 mm3, mice were randomly assigned into one of the groups receiving vehicle, sorafenib, ENMD-2076 alone or in combination with chemotherapy agents, including doxorubicin or 5-FU, respectively, for 20 days. Results: In all HCC models tested, ENMD-2076 induced tumor growth inhibition significantly greater than that of sorafenib. When treated with ENMD-2076 at 100 mg/kg, the tumor growth inhibition (TGI) rates were 73.67%, 76.59% or 80.12% in the SMMC-7721, QGY-7703 or HepG 2 models, respectively, which were significantly higher than those observed in sorafenib treated groups (48.63%, 51.43%, or 57.60%, respectively;P<0.01 in all three models). Tumor growth inhibition rates were similarly higher in the ENMD-2076 treated groups than in groups treated with doxorubicin at 1 mg/kg and 5-FU at 30 mg/kg. The combined treatment of ENMD-2076 with either doxorubicin or 5-FU was well tolerated. Higher TGI rates were observed in combination groups compared to single agents of chemotherapies but were not statistically different. Conclusion: ENMD-2076 showed robust antitumor activity against three cell line-derived xenograft models of HCC superior to that of sorafenib, doxorubicin, and 5FU, supporting clinical investigation of this agent in HCC patients who do not tolerate, or have failed or relapsed from other systemic treatment such as sorafenib, doxorubicin or 5 FU. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C265. Citation Format: Peipei Yin, Hongqi Lu, Mark R. Bray, Bingsheng Li, Ken Ren. Significant in vivo activity of ENMD-2076, a novel multi-targeted kinase inhibitor, towards xenograft models of human hepatocellular carcinomas . [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C265.
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 | 0,000 |
| 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 ».