Biology subjects

Tsai, Y.-F.

Publications and source records attributed to Tsai, Y.-F..

3 recordsLinked to original sources

bioRxiv2025

Association of GADD45A and favorable outcome in hormone positive breast cancer

BackgroundHormone receptor-positive (HR(+)) breast cancer is the most prevalent subtype in breast cancer, and although treatment options are rapidly increasing, still poses as an unmet need in advanced cases. Growth arrest and DNA damage-inducible alpha (GADD45A) is a gene with known relationship with the cell cycle and DNA damage pathways. Conflicting roles in breast cancer biology have been reported for GADD45A. In our study, we investigate the clinical and molecular association of GADD45A in HR(+) breast cancer, evaluating its prognostic potential and relationship with estrogen signaling. MethodsGADD45A expression was assessed in 100 breast cancer tissue samples from a tissue microarray and correlated with clinicopathologic parameters. Public genomic datasets were analyzed to validate associations between GADD45A expression and clinical outcomes in HR(+)HER2(-) breast cancer. Gene set enrichment analysis (GSEA) was used to investigate pathway correlations. ResultsGADD45A protein levels were highest in HR(+)HER2(-) tumors and positively correlated with estrogen receptor (ER) levels, consistent with a luminal phenotype. No significant association was observed between GADD45A levels and progression-free survival in CDK4/6 inhibitor-treated patients, suggesting limited predictive utility in this context. However, higher GADD45A expression was significantly associated with improved overall and relapse-free survival in HR(+)HER2(-) breast cancer in the METABRIC cohort, but not in HER2(+) or triple- negative subtypes. GSEA revealed a positive association between GADD45A expression and the estrogen late response signature, suggesting a functional link with hormone signaling. ConclusionGADD45A expression is enriched in luminal-type HR(+) breast cancer and correlates with favorable clinical outcomes. While not predictive of CDK4/6 inhibitor response, GADD45A may serve as a surrogate marker of estrogen signaling and improved prognosis. These findings support further investigation into GADD45A as a biomarker for stratification and potentially as a therapeutic target in HR(+) breast cancer.

cancer biology↗

bioRxiv2018

Propofol inhibits endogenous formyl peptide-induced neutrophil activation and alleviates lung injury

Critically ill patients have a high risk of sepsis. Various studies have demonstrated that propofol has anti-inflammatory effects that may benefit critically ill patients who require anesthesia. However, the mechanism and therapeutic effect remain incompletely understood. Our previous data suggest that propofol can act as a formyl peptide receptor 1 (FPR1) antagonist. Here, we hypothesize that propofol mitigates sepsis-induced acute lung injury (ALI) by inhibiting mitochondria-derived N-formyl peptide-mediated neutrophil activation. In human neutrophils, propofol competitively reduced the release of elastase, superoxide, and reactive oxygen species induced by fMMYALF, a human mitochondria-derived N-formyl peptide. In addition, propofol significantly inhibited fMMYALF-induced chemotaxis, calcium mobilization, and phosphorylation of protein kinase B and mitogen-activated protein kinases. These results indicate that propofol suppresses neutrophil activation by blocking the interaction between endogenous N-formyl peptide and its receptor, FPR1, thus inhibiting downstream signaling. Furthermore, propofol alleviated alveolar wall disruption, edematous changes, and neutrophil infiltration in lipopolysaccharide-induced ALI in mice. Noticeably, propofol improved the survival of sepsis mice. This study indicates that the anti-neutrophil effects of propofol may benefit critically ill septic patients.

pharmacology and toxicology↗

bioRxiv2018

Targeting redox regulatory site of protein kinase B impedes neutrophilic inflammation

Neutrophil activation has a pathogenic effect in inflammatory diseases. Protein kinase B (PKB)/AKT regulates diverse cellular responses. However, the significance of AKT in neutrophilic inflammation is still not well understood. Here, we identified CLLV-1 as a novel AKT inhibitor. CLLV-1 inhibited respiratory burst, degranulation, chemotaxis, and AKT phosphorylation in activated human neutrophils and dHL-60 cells. Significantly, CLLV-1 blocked AKT activity and covalently reacted with AKT Cys310 in vitro. The AKT309-313 peptide-CLLV-1 adducts were determined by NMR or mass spectrometry assay. The alkylation agent-conjugated AKT (reduced form) level was also inhibited by CLLV-1. Additionally, CLLV-1 ameliorated lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. CLLV-1 acts as a covalent allosteric AKT inhibitor by targeting AKT Cys310 to restrain inflammatory responses in human neutrophils and LPS-induced ALI in vivo. Our findings provide a mechanistic framework for redox modification of AKT that may serve as a novel pharmacological target to alleviate neutrophilic inflammation.

pharmacology and toxicology↗