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

Abnormal activation of signal transducer and activator of transcription 3 (STAT3) transcription factor has been observed in many human cancers with roles in tumor initiation, progression, drug resistance, angiogenesis and immunosuppression. STAT3 is constitutively activated in a variety of cancers including adult high grade gliomas (aHGGs) such as glioblastoma (GBM), and pediatric high grade gliomas (pHGG). Inhibiting STAT3 is a promising target-specific chemotherapeutic strategy for tumors with aberrant STAT3 signaling. Here we investigated the antitumor effects of novel pyrazole-based STAT3 pathway inhibitors named MNS1 (Mayo Neurosurgery 1) in both pediatric and adult HGG tumor cells. MNS1 compounds selectively decreased cell viability and proliferation in patient-derived HGG cells with minimal toxicity on normal human astrocytes. These inhibitors selectively blocked IL-6-induced STAT3 phosphorylation and nuclear localization of pSTAT3 without affecting other signaling molecules including Akt, STAT1, JAK2 or ERK1/2 phosphorylation. Functional analysis showed that MNS1 compounds induced apoptosis and decrease tumor migration. The anti-tumor effects extended into a murine pHGG (diffuse intrinsic pontine glioma) patient derived xenograft, and systemic toxicity was not evident during dose escalation in mice. These results support further development of STAT3 inhibitors for both pediatric and adult HGG.

Antitumor activity of novel pyrazole-based small molecular inhibitors of the STAT3 pathway in patient derived high grade glioma cells