Notably, pimozide exhibited anti-tumor effects as a monotherapy and in combination with paclitaxel at clinically relevant doses. While tumor volume reduction in the combination group was not statistically greater than that in the monotherapy group, fluorescence immunohistochemistry revealed a marked decrease in undifferentiated tumor cells, indicating enhanced therapeutic effects of combination treatment. Taken together, these findings indicate that pimozide is a promising candidate for repurposing as a novel therapeutic agent against HNSCC.
15 days ago
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STAT3 (Signal Transducer And Activator Of Transcription 3) • DRD2 (Dopamine Receptor D2) • EGR1 (Early Growth Response 1)
Although FLT3 tyrosine kinase inhibitors (TKIs), such as quizartinib (Quiz) and gilteritinib, have improved clinical outcomes, secondary TKD mutations, particularly the gatekeeper mutation F691L, confer significant resistance. Expression of constitutively active STAT5 partially rescued CPZ-induced growth inhibition. These findings suggest that STAT5 suppression is a key mechanism of CPZ's antileukemic activity and support its potential as a therapeutic strategy for FLT3-ITD-positive AML.
1 month ago
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FLT3 (Fms-related tyrosine kinase 3) • STAT5A (Signal Transducer And Activator Of Transcription 5A)
In this study, drug repurposing agent's metformin, chlorpromazine (CPZ) alone and combine were tested on both clinical and laboratory ovarian cancer samples to evaluate on hemocytometer and clonogenic assay for dead cell and proliferation respectively. The resulting data were analyzed to achieve successfully known target region and worked as a bridge between clinical and laboratory model. The insights gained from this study not only validate OVCAR3 as a representative model for HGSOC but also provide a foundation for developing targeted therapeutic strategies.
Our data reveal novel insights into the role of amisulpride in modulating the differential expression of genes and proteins. These findings, which involve genes/proteins related to AP-1 transcription factor family gene regulation, cytoskeleton, histone binding activity, the intracellular trafficking of receptors and endocytosis of a variety of macromolecules, and nuclear localization signal, are particularly significant as they shed light on the molecular underpinnings of the clinical efficacy of amisulpride and the pathogenesis of schizophrenia.
3 months ago
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CLTC (Clathrin Heavy Chain) • ACTG1 (Actin Gamma 1)
There was higher overall risk of SI in patients with chronic schizophrenia. SI might be associated with psychotic symptoms, depression, insomnia, medication side effects, and increased levels of inflammatory cytokines. In clinical practice, doctors should take prompt preventive measures in patients combining suicidal risk factors.
In patient-derived xenograft (PDX) models, combined therapy of clathrin inhibitor (chlorpromazine) or SH3KBP1 silencing with sorafenib suppresses tumor growth and reduces microvascular density. This study demonstrates that CLTB promotes HCC progression through the NF-κB-PCLAF signaling axis and sEV-mediated vascular remodeling, providing a mechanistic foundation for developing combination therapies targeting CLTB.
One week of aripiprazole administration in healthy participants altered brain Glx levels as compared with placebo administration. These findings provide novel insights into the relationship between antipsychotic treatment and brain metabolites in a healthy participant cohort.