English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Objective  Neurofibromatosis type 1 (NF1) is a hereditary tumor syndrome characterized by an increased risk of malignant peripheral nerve sheath tumors (MPNST). Chemotherapy of MPNST is still insufficient. In this study, we investigated whether human tumor Schwann cells derived from NF1 associated MPNST respond to all- trans  retinoic acid (ATRA). We analyzed effects of ATRA and MEK inhibitor (MEKi) combination therapy.    Methods  MPNST cell lines S462, T265, NSF1 were treated with ATRA and MEKi U0126 and PD0325901. We assessed cell viability, proliferation, migration, apoptosis and differentiation as well as mRNA expression of  RAR  and  RXR  subtypes and ATRA target genes such as  CRABP2 ,  CYP26A1 ,  RARB  and  PDK1 . We also analyzed  CRABP2  methylation in cell lines and performed immunohistochemistry of human MPNST specimens.    Results  ATRA therapy reduced viability and proliferation in S462 and T265 cells, accompanied by differentiation, apoptosis and reduced migration. NSF1 cells which lacked  RXRG  expression did not respond to ATRA. We furthermore demonstrated that ATRA signaling was functional for common targets, and that mRNA expression of  CRABP2  and its targets was raised by ATRA therapy, whereas alternative pathways via  FABP5  were not induced. Finally, combination of ATRA and MEKi demonstrated additively reduced viability of T265 and S462 cells.    Conclusions  We observed therapeutic effects in two of three MPNST cell lines pronounced by combination therapy. These data point to a potentially successful treatment of MPNST by combined application of ATRA and MEK inhibitors such as U0126 or PD0325901.

MEK inhibitors enhance therapeutic response towards ATRA in NF1 associated malignant peripheral nerve sheath tumors (MPNST) in-vitro