727 ANTISENSE OLIGONUCLEOTIDE TARGETING INSULIN-LIKE GROWTH FACTOR-1 RECEPTOR ENHANCES PACLITAXEL SENSITIVITY IN A PACLITAXEL- RESISTANT PROSTATE CANCER MODEL
Notice bibliographique
Résumé
You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 2011727 ANTISENSE OLIGONUCLEOTIDE TARGETING INSULIN-LIKE GROWTH FACTOR-1 RECEPTOR ENHANCES PACLITAXEL SENSITIVITY IN A PACLITAXEL- RESISTANT PROSTATE CANCER MODEL Junya Furukawa, Hideaki Miyake, Masato Fujisawa, Christopher Wraight, Brett Monia, Martin Gleave, and Michael Cox Junya FurukawaJunya Furukawa Kobe, Japan More articles by this author , Hideaki MiyakeHideaki Miyake Kobe, Japan More articles by this author , Masato FujisawaMasato Fujisawa Kobe, Japan More articles by this author , Christopher WraightChristopher Wraight Victoria, Australia More articles by this author , Brett MoniaBrett Monia Carlsbad, CA More articles by this author , Martin GleaveMartin Gleave Vancouver, Canada More articles by this author , and Michael CoxMichael Cox Vancouver, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1696AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Altered expression of insulin-like growth factor (IGF) axis components have been consistently found in prostate cancer (PCa) and associated with adaptive growth and survival signaling implicated in castrate-resistant disease (CRPC) progression. These activities are mediated by activation of the IGF-I receptor (IGF-IR). While CRPC patients treated with taxanes alone or in combination with estramustine phosphate or predonisone show a survival benefit, development of chemotherapeutic resistance eventually occurs. Therefore novel strategies targeting the molecular basis of androgen deprivation therapy and chemotherapy resistance are required. In this study, we establish paclitaxel-resistant androgen-independent PCa cells (PtxR PC3) and assess the potency and anti-cancer activity of a 2 EMOE-modified antisense oligonucleotide (ASO) targeting human IGF-IR, ATL1101, on PtxR PC3 cells in vitro and in vivo. METHODS PtxR PC3 cells were established by culturing in step-wise increased drug concentrations. IGF-IR mRNA and protein expression in ATL1101- and control oligonucleotides (ODN)-treated PtxR PC3 cells were measured by QT-PCR and immunoblotting. The effect of IGF-1R ASO and paclitaxel combination therapy on PtxR PC3 cell growth and apoptosis in vitro was examined by crystal violet assay and flow cytometry. In vitro combination index (CI) was calculated by Calcusyn® softoware. For in vivo xenograft studies, PtxR PC-3 cells were inoculated s.c. in the flanks of athymic nude mice and tumor volume kinetics were compared for mice treated with paclitaxel injected i.v. and either ATL1101 or control ODN injected i.p. RESULTS The IC50 for paclitaxel in PtxR PC3 was 15-fold higher than that in parental cells. PtxR PC3 also shows cross-resistance to docetaxel and mitoxantrone. We observed dose- and sequence-specific suppression of IGF-IR mRNA and protein expression in ATL1101-treated PtxR PC3 cells in vitro which correlated with decreased proliferation and increased apoptosis of PtxR PC3 cells. Combination of ATL1101 with paclitaxel showed CI values below 1 at the IC50, IC75, suggesting the drug interactions resulted in synergy. Compared to control ODN, ATL1101 significantly suppressed PtxR PC3 tumor growth as a combination therapy with paclitaxel in murine xenografts. CONCLUSIONS This study reports the first preclinical proof-of-principle data that this novel IGF-IR ASO suppresses growth of paclitaxel resistant PC tumors, synergistically enhancing paclitaxel sensitivity in vitro and in vivo. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e292 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Junya Furukawa Kobe, Japan More articles by this author Hideaki Miyake Kobe, Japan More articles by this author Masato Fujisawa Kobe, Japan More articles by this author Christopher Wraight Victoria, Australia More articles by this author Brett Monia Carlsbad, CA More articles by this author Martin Gleave Vancouver, Canada More articles by this author Michael Cox Vancouver, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
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 | 0,001 |
| Bibliométrie | 0,001 | 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) | 0,007 | 0,002 |
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 ».