Project description:Purpose: Androgen-deprivation therapy is the standard treatment for prostate cancer but fails in hormone-refractory prostate cancer. The anti-inflammatory plant Wedelia chinensis is rich in luteolin, apigenin, and wedelolactone that act synergistically to suppress androgen receptor activity in prostate cancer. Here, we evaluated the systemic antitumor effects of a standardized and effect-optimized Wedelia chinensis herbal extract (WCE) on hormone-refractory prostate cancer. Methods: Hormone-refractory PC-3 orthotopic tumor mouse models were orally administered with WCE. The tumor transcriptomes were studied using RNA sequencing and Ingenuity Pathway Analysis to identify the molecular mechanisms. Results: WCE significantly attenuated tumor growth and metastasis in orthotopic PC-3 xenografts. Transcriptomic analysis of genome-wide gene expression in the tumors revealed that WCE suppressed the expression of HIF1α, IKKα/β phosphorylation, and the downstream cytokines/chemokines. Conclusions: A standardized preparation of Wedelia chinensis improved prostate cancer therapy through repressing NFκB-mediated cytokine expression in tumor cells and modulating the inflammatory tumor microenvironment. These data suggest that WCE functions through immunomodulation and has potential application as an adjuvant agent for the treatment of castration-resistant prostate cancer.
Project description:Recurrences of hormone-refractory prostate cancer highly affect the therapeutic outcome. Although anti-androgen therapy prolongs survival in prostate cancer patients, resistance rapidly develops and is often associated with increased androgen receptor expression and upregulated HER2/3-AKT signaling pathway. However, single agent therapy targeting AR, HER2/3 or AKT usually failed due to the reciprocal feedback loop. Here, we demonstrated that herbal extract of Wedelia chinensis (WCE) effectively disrupted the androgen receptor, HER2/3, and AKT signaling network and therefore enhanced therapeutic efficacy of androgen ablation in PCa.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression. Two-condition experiment, Normoxic MSCs vs. Hypoxic MSCs.
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.