Abstract 1118: Role of the type I insulin-like growth factor receptor in lung tumorigenesis
Notice bibliographique
Résumé
Abstract Lung cancer is the leading cause of cancer related mortalities worldwide. The type I insulin-like growth factor receptor (IGF-IR) is frequently expressed at high levels in lung cancer. This receptor is involved in cell proliferation, apoptosis, migration and differentiation and is emerging as a potential target for molecular therapies. Furthermore, IGF-IR downregulation has been reported to sensitize cancer cells to agents that promote apoptosis. To investigate the importance of the IGF-IR in lung tumorigenesis, our lab generated doxycycline-inducible transgenic mice in which the IGF-IR was overexpressed in type II alveolar or Clara cells. IGF-IR overexpression was sufficient to induce lung tumor development in these mice indicating that this receptor has an important function in the initiation of lung tumorigenesis. To further investigate the role of IGF-IR in lung tumorigenesis, the levels and function of IGF-IR were evaluated in two human lung tumor cell lines (A549 and NCI-H358) and one murine lung tumor cell line (LA-4) as well as in human and murine normal bronchial epithelial cells. Western blotting revealed increased levels of IGF-IR in the lung cancer cell lines compared to the normal lung epithelial cells lines. The efficacy of the IGF-IR small-molecule inhibitor, BMS-754807, which is a drug currently in clinical trials, was also evaluated in the lung tumor cells. BMS-754807 inhibited A549, NCI-H358 and LA-4 cell survival in a dose-dependent manner with approximate IC50 concentrations of 1.70uM for A549, 1.25uM for NCI-H358 and 0.74uM for LA-4 cells. The effects of BMS-754807 on cell proliferation (Ki67 immunofluorescence), cell survival (JC-1 immunofluorescence) and migration (scratch wound and Boyden chamber assays) are currently being examined to determine which properties are affected by disruption of IGF-IR signaling. Similar studies will be performed following downregulation of IGF-IR expression using RNAi. To evaluate whether BMS-754807 could sensitize lung tumor cells to the cytotoxic effects of chemotherapeutic agents commonly employed in the treatment of human lung cancer, BMS-754807 was combined with cisplatin and with carboplatin. Neither the BMS-754807/cisplatin nor the BMS-754807/carboplatin combinations appeared to have a synergistic effect on cell survival. Combinations of BMS-754807 and lung cancer chemotherapeutic agents that do not target DNA are currently being evaluated. Additionally, key downstream molecules of the IGF-IR, including Akt and ERK1/2, are being studied as well as the transcription factor, KLF5, which is expressed at high levels in the lung tumors of the IGF-IR transgenic mice. Initial results support the importance of IGF-IR signaling in lung cancer. Further understanding of the function of IGF-IR in lung cancer will enable the development of more effective targeted therapies and improve existing therapeutic strategies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1118. doi:10.1158/1538-7445.AM2011-1118
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) | 0,003 | 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 ».