71 research outputs found

    A chemical probe for BAG1 targets androgen receptor-positive prostate cancer through oxidative stress signaling pathway

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    BAG1 is a family of polypeptides with a conserved C-terminal BAG domain that functions as a nucleotide exchange factor for the molecular chaperone HSP70. BAG1 proteins also control several signaling processes including proteostasis, apoptosis and transcription. The largest isoform, BAG1L, controls the activity of the androgen receptor (AR) and is upregulated in prostate cancer. Here, we show that BAG1L regulates AR dynamics in the nucleus and its ablation attenuates AR target gene expression especially those involved in oxidative stress and metabolism. We show that a small molecule, A4B17 that targets the BAG domain downregulates AR target genes similar to a complete BAG1L knockout and upregulates the expression of oxidative stress-induced genes involved in cell death. Furthermore, A4B17 outperformed the clinically approved antagonist enzalutamide in inhibiting cell proliferation and prostate tumor development in a mouse xenograft model. BAG1 inhibitors therefore offer unique opportunities for antagonizing AR action and prostate cancer growth

    Splenogonadal fusion.

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    Treatment of idiopathic and postvaricocelectomy oligozoospermia with oral tamoxifen citrate

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    Objective To identify a subgroup of men who may benefit from tamoxifen citrate (a widely prescribed drug for male infertility) among those with normogonadotrophic and hypergonadotrophic oligozoospermia, either idiopathic or after varicocelectomy

    New urinary antigens as markers in bladder cancer

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    Bladder cancer is one of the most common cancer types in men. Recently, new bladder tumor antigens have been isolated from the urine of bladder cancer patients found positive by histology. In this study, urothelial tumor antigens UBC (Urinary Bladder Cancer) and by the BTA(stat) (Bladder Tumor Antigen) were measured test in urine of 56 patients with bladder cancer, by ELISA and immunochromatographic tests, respectively. A control group of 20 healthy subjects was also taken into the study. UBC levels were significantly higher in 64.3 % of the patients. BTA(stat) test was found positive in 40 % of the patients. We conclude that both tests may help in the diagnosis and follow-up of bladder cancer
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