FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2335380014> ?p ?o ?g. }

• W2335380014 abstract "Background: Standard 2D monolayer cultures used for target validation and drug screening studies do not adequately address the complexity of in vivo tumor pathophysiology. Although 3D tumor spheroids better represent a tumor microenvironment (with gradients of proliferation, oxygenation and drug access) they have not been routinely used in high-throughput (HTS) mode. The aim of the present study was to develop a suite of in vitro 3D spheroid-based assays to rapidly and accurately quantify key aspects of the malignant phenotype: growth, motility, invasion and angiogenesis. Methods: We established a novel, standardised method for the generation of tumor spheroids in suspension using ultra-low attachment (ULA) 96-well plates. Spheroids were characterized in terms of growth kinetics, haptotaxis on extracellular matrix (ECM) and endothelial cell (EC) monolayers, invasion into MatrigelTM and co-culture with embryoid bodies (EB) to model tissue invasion/angiogenesis. Quantitative data were obtained by image analysis using a Celigo cytometer or microscopy. Cell viability was determined by the CellTiter Glo assay for direct comparison of 2D and 3D cultures. Highly malignant human adult (U87MG) and pediatric (KNS42) gliomas and breast carcinoma (MDA MB 231) spheroids were treated with inhibitors of HSP90 (17-AAG) and PI3K (PI-103) to demonstrate the power of the techniques. Results: Our standardized protocol generates single spheroids/well which are reproducible in size and easy to handle. Images are obtained at intervals over 14 days for growth kinetics or 48-96 hours for functional assays. The Celigo cytometer enables rapid, multiparametric real-time analyses, and samples can be collected to measure target protein expression, drug levels and pharmacodynamic effects. Dose-dependent inhibition of 3D spheroids was readily demonstrated using the targeted agents 17-AAG and PI-103. All models also showed extensive migration and invasion mirroring their in-vivo behaviour; interestingly U87MG and KNS42 showed different patterns of dissemination: widely dispersed or contiguous respectively. MDA MB 231 migration and invasion were inhibited with sub GI50 concentrations of 17-AAG. GFP-labeled U87MG and MDA MB 231 tumor spheroids co-cultured with EBs rapidly attached and coalesced, providing a model to study simultaneous tissue invasion and angiogenesis. Direct comparisons of cell viability in 2D and 3D showed that U87MG and MDA MB 231 are more resistant to 17-AAG in 3D, conversely U87MG was more sensitive to PI-103 in 3D. Conclusions: We have developed a unique repertoire of novel 3D multiplate assays reflecting key aspects of malignant cell behaviour and able to deliver rapid and reproducible results. We provide evidence that our methods potentially enhance target selection and the triaging of drug candidates prior to in vivo studies. 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 4277. doi:10.1158/1538-7445.AM2011-4277" @default.
• W2335380014 created "2016-06-24" @default.
• W2335380014 creator A5015731749 @default.
• W2335380014 creator A5019593377 @default.
• W2335380014 creator A5025972115 @default.
• W2335380014 creator A5031760532 @default.
• W2335380014 creator A5043790154 @default.
• W2335380014 creator A5087926888 @default.
• W2335380014 date "2011-04-15" @default.
• W2335380014 modified "2023-09-27" @default.
• W2335380014 title "Abstract 4277: High throughput 3D tumor spheroid assays for target validation and drug evaluation" @default.
• W2335380014 doi "https://doi.org/10.1158/1538-7445.am2011-4277" @default.
• W2335380014 hasPublicationYear "2011" @default.
• W2335380014 type Work @default.
• W2335380014 sameAs 2335380014 @default.
• W2335380014 citedByCount "0" @default.
• W2335380014 crossrefType "proceedings-article" @default.
• W2335380014 hasAuthorship W2335380014A5015731749 @default.
• W2335380014 hasAuthorship W2335380014A5019593377 @default.
• W2335380014 hasAuthorship W2335380014A5025972115 @default.
• W2335380014 hasAuthorship W2335380014A5031760532 @default.
• W2335380014 hasAuthorship W2335380014A5043790154 @default.
• W2335380014 hasAuthorship W2335380014A5087926888 @default.
• W2335380014 hasConcept C142724271 @default.
• W2335380014 hasConcept C150903083 @default.
• W2335380014 hasConcept C175369904 @default.
• W2335380014 hasConcept C185592680 @default.
• W2335380014 hasConcept C202751555 @default.
• W2335380014 hasConcept C203014093 @default.
• W2335380014 hasConcept C207001950 @default.
• W2335380014 hasConcept C2776107976 @default.
• W2335380014 hasConcept C2780394083 @default.
• W2335380014 hasConcept C3020616263 @default.
• W2335380014 hasConcept C502942594 @default.
• W2335380014 hasConcept C553184892 @default.
• W2335380014 hasConcept C55493867 @default.
• W2335380014 hasConcept C71924100 @default.
• W2335380014 hasConcept C86803240 @default.
• W2335380014 hasConceptScore W2335380014C142724271 @default.
• W2335380014 hasConceptScore W2335380014C150903083 @default.
• W2335380014 hasConceptScore W2335380014C175369904 @default.
• W2335380014 hasConceptScore W2335380014C185592680 @default.
• W2335380014 hasConceptScore W2335380014C202751555 @default.
• W2335380014 hasConceptScore W2335380014C203014093 @default.
• W2335380014 hasConceptScore W2335380014C207001950 @default.
• W2335380014 hasConceptScore W2335380014C2776107976 @default.
• W2335380014 hasConceptScore W2335380014C2780394083 @default.
• W2335380014 hasConceptScore W2335380014C3020616263 @default.
• W2335380014 hasConceptScore W2335380014C502942594 @default.
• W2335380014 hasConceptScore W2335380014C553184892 @default.
• W2335380014 hasConceptScore W2335380014C55493867 @default.
• W2335380014 hasConceptScore W2335380014C71924100 @default.
• W2335380014 hasConceptScore W2335380014C86803240 @default.
• W2335380014 hasLocation W23353800141 @default.
• W2335380014 hasOpenAccess W2335380014 @default.
• W2335380014 hasPrimaryLocation W23353800141 @default.
• W2335380014 hasRelatedWork W1991152302 @default.
• W2335380014 hasRelatedWork W2004349971 @default.
• W2335380014 hasRelatedWork W2007131420 @default.
• W2335380014 hasRelatedWork W2020787750 @default.
• W2335380014 hasRelatedWork W2087779453 @default.
• W2335380014 hasRelatedWork W2105547345 @default.
• W2335380014 hasRelatedWork W2122778942 @default.
• W2335380014 hasRelatedWork W2138969252 @default.
• W2335380014 hasRelatedWork W2139799760 @default.
• W2335380014 hasRelatedWork W2299670289 @default.
• W2335380014 hasRelatedWork W2331044295 @default.
• W2335380014 hasRelatedWork W2335021307 @default.
• W2335380014 hasRelatedWork W2366239624 @default.
• W2335380014 hasRelatedWork W2411123878 @default.
• W2335380014 hasRelatedWork W2508201086 @default.
• W2335380014 hasRelatedWork W2621479854 @default.
• W2335380014 hasRelatedWork W2741847891 @default.
• W2335380014 hasRelatedWork W2761453789 @default.
• W2335380014 hasRelatedWork W3095223809 @default.
• W2335380014 hasRelatedWork W80479032 @default.
• W2335380014 isParatext "false" @default.
• W2335380014 isRetracted "false" @default.
• W2335380014 magId "2335380014" @default.
• W2335380014 workType "article" @default.