FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2560924103> ?p ?o ?g. }

• W2560924103 abstract "Background: The tumor microenvironment (TME) plays an important role in neuroblastoma (NBL) biology. Infiltrations of tumor-associated macrophages with alterations in patterns of pro-inflammatory genes are associated with poor prognosis in NBL. However, the role of regulatory T-cells in NBL remains unknown. As several genes in MAPK pathway are among recurrent mutations in neuroblastomas, and the production of pro-inflammatory mediators in immune cells is MAPK-dependent, we hypothesized targeted kinase inhibitor in combination with check-point blockade could exert synergistic effects on the TME9s response to tumor cells. Therefore, we assessed the efficacy of combined therapy using a transgenic MYCN non-amplified neuroblastoma murine model driven by SV40 large T antigen (NB-Tag). Methods: Three human neuroblastoma cell lines and two NB-Tag derived mouse cell-lines were used for in vitro cell proliferation assay. For in vivo tumor growth models, combinations of cyclophosphamide, topotecan, trametinib, anti-CTLA4, and anti-PD1 therapies were studied in NB-Tag transgenic and transplantable subcutaneous (NB-SQ) murine models. Results: In vitro studies demonstrated trametinib had the highest anti-proliferative activity compared to other kinase inhibitors, and it effectively blocked cell cycle arrest in G1 phase. These anti-proliferative effects could not be rescued by co-culturing tumor cells with murine or human macrophages. In NB-Tag mice, which develop neuroblastoma spontaneously at 12 weeks, daily oral administration of trametinib (0.6mg/Kg) at pre-tumoral age (10 wk) significantly impaired tumor growth by 17 weeks (1424 mm3 in controls vs. 43 mm3 in treated mice). Treatment of 15 week-old NB-Tag mice (visible tumor by MRI) with trametinib after chemotherapy administration (5-days of Cyclophosphamide + Topotecan) also significantly impaired tumor regrowth (volume four weeks post-chemo, 491 vs. 42 mm3, p = 0.037), and more importantly, treatment increased the survival of NB-Tag mice compared to control (median survival: control = 24.5 wk, treated = 35 wk, p Conclusions: Our results provide strong evidence that MEK inhibition combined with checkpoint blockade significantly inhibited tumor formation in a syngeneic subcutaneous model. These findings indicate opportunities to enhance antitumor immunity with the potential to produce durable clinical responses in children with neuroblastomas. Citation Format: Sakunthala Muthugounder, Long Hung, Randall Chan, Jin Kim, Soheila Shirinbak, Hiroyuki Shimada, Shahab Asgharzadeh. MEK inhibition enhances immune checkpoint blockade treatment of murine models of neuroblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 400. doi:10.1158/1538-7445.AM2015-400" @default.
• W2560924103 created "2017-01-06" @default.
• W2560924103 creator A5008628156 @default.
• W2560924103 creator A5028090905 @default.
• W2560924103 creator A5033658807 @default.
• W2560924103 creator A5038890216 @default.
• W2560924103 creator A5042344336 @default.
• W2560924103 creator A5089598556 @default.
• W2560924103 creator A5090409397 @default.
• W2560924103 date "2015-08-01" @default.
• W2560924103 modified "2023-09-26" @default.
• W2560924103 title "Abstract 400: MEK inhibition enhances immune checkpoint blockade treatment of murine models of neuroblastoma" @default.
• W2560924103 doi "https://doi.org/10.1158/1538-7445.am2015-400" @default.
• W2560924103 hasPublicationYear "2015" @default.
• W2560924103 type Work @default.
• W2560924103 sameAs 2560924103 @default.
• W2560924103 citedByCount "0" @default.
• W2560924103 crossrefType "proceedings-article" @default.
• W2560924103 hasAuthorship W2560924103A5008628156 @default.
• W2560924103 hasAuthorship W2560924103A5028090905 @default.
• W2560924103 hasAuthorship W2560924103A5033658807 @default.
• W2560924103 hasAuthorship W2560924103A5038890216 @default.
• W2560924103 hasAuthorship W2560924103A5042344336 @default.
• W2560924103 hasAuthorship W2560924103A5089598556 @default.
• W2560924103 hasAuthorship W2560924103A5090409397 @default.
• W2560924103 hasConcept C184235292 @default.
• W2560924103 hasConcept C203014093 @default.
• W2560924103 hasConcept C2776107976 @default.
• W2560924103 hasConcept C2776715637 @default.
• W2560924103 hasConcept C2778472372 @default.
• W2560924103 hasConcept C502942594 @default.
• W2560924103 hasConcept C54355233 @default.
• W2560924103 hasConcept C57074206 @default.
• W2560924103 hasConcept C71924100 @default.
• W2560924103 hasConcept C81885089 @default.
• W2560924103 hasConcept C86803240 @default.
• W2560924103 hasConcept C8891405 @default.
• W2560924103 hasConcept C95444343 @default.
• W2560924103 hasConceptScore W2560924103C184235292 @default.
• W2560924103 hasConceptScore W2560924103C203014093 @default.
• W2560924103 hasConceptScore W2560924103C2776107976 @default.
• W2560924103 hasConceptScore W2560924103C2776715637 @default.
• W2560924103 hasConceptScore W2560924103C2778472372 @default.
• W2560924103 hasConceptScore W2560924103C502942594 @default.
• W2560924103 hasConceptScore W2560924103C54355233 @default.
• W2560924103 hasConceptScore W2560924103C57074206 @default.
• W2560924103 hasConceptScore W2560924103C71924100 @default.
• W2560924103 hasConceptScore W2560924103C81885089 @default.
• W2560924103 hasConceptScore W2560924103C86803240 @default.
• W2560924103 hasConceptScore W2560924103C8891405 @default.
• W2560924103 hasConceptScore W2560924103C95444343 @default.
• W2560924103 hasLocation W25609241031 @default.
• W2560924103 hasOpenAccess W2560924103 @default.
• W2560924103 hasPrimaryLocation W25609241031 @default.
• W2560924103 hasRelatedWork W1160892457 @default.
• W2560924103 hasRelatedWork W1551112729 @default.
• W2560924103 hasRelatedWork W1945191148 @default.
• W2560924103 hasRelatedWork W2064845571 @default.
• W2560924103 hasRelatedWork W2085563981 @default.
• W2560924103 hasRelatedWork W2090475773 @default.
• W2560924103 hasRelatedWork W2342907620 @default.
• W2560924103 hasRelatedWork W2395000660 @default.
• W2560924103 hasRelatedWork W2476540671 @default.
• W2560924103 hasRelatedWork W2483180845 @default.
• W2560924103 hasRelatedWork W2493130567 @default.
• W2560924103 hasRelatedWork W2537973974 @default.
• W2560924103 hasRelatedWork W2740744394 @default.
• W2560924103 hasRelatedWork W2740838549 @default.
• W2560924103 hasRelatedWork W2802364378 @default.
• W2560924103 hasRelatedWork W2885147819 @default.
• W2560924103 hasRelatedWork W2954295954 @default.
• W2560924103 hasRelatedWork W3082482509 @default.
• W2560924103 hasRelatedWork W3180806010 @default.
• W2560924103 hasRelatedWork W3182464748 @default.
• W2560924103 isParatext "false" @default.
• W2560924103 isRetracted "false" @default.
• W2560924103 magId "2560924103" @default.
• W2560924103 workType "article" @default.