Castration-recurrent prostate cancer (CRPC) is suspected to depend on androgen receptor (AR). The AF-1 region in the amino-terminal domain (NTD) of AR contains most, if not all, of the transcriptional activity. Here we identify EPI-001, a small molecule that blocked transactivation of the NTD and was specific for inhibition of AR without attenuating transcriptional activities of related steroid receptors. EPI-001 interacted with the AF-1 region, inhibited protein-protein interactions with AR, and reduced AR interaction with androgen-response elements on target genes. Importantly, EPI-001 blocked androgen-induced proliferation and caused cytoreduction of CRPC in xenografts dependent on AR for growth and survival without causing toxicity.

Purpose To assess the microarchitectural changes occurring during surgery for vitreomacular traction (VMT) utilizing intraoperative optical coherence tomography (iOCT). Methods A retrospective, consecutive, case series of eyes undergoing pars plana vitrectomy (PPV) for VMT with performance of concurrent iOCT. A custom, microscope-mounted, portable, spectral domain optical coherence tomography (SD-OCT) system was used. Clinical characteristics and iOCT images were analyzed. Results Twelve eyes of 12 patients were included with a mean preoperative visual acuity (VA) of 20/78 improving to 20/51 (p = 0.02), post-operatively. iOCT was successfully performed in 100% of cases. Microarchitectural changes were noted on iOCT following surgical release of the VMT particularly in the outer retina with increased subretinal hyporeflectivity (e.g., expansion of the distance between the RPE and photoreceptor layers). In 5/12 (42%) eyes, iOCT findings altered the surgical procedure (e.g., internal limiting membrane peeling, gas tamponade) to address the subclinical findings [e.g., full-thickness macular hole (FTMH) formation, residual membrane]. Conclusions Intrasurgical imaging utilizing iOCT during VMT surgery may identify subclinical changes (e.g., occult FTMH formation) that may impact surgical decision-making. Architectural changes may occur following surgical maneuvers that are particularly noted in the outer retina. The functional significance of these changes requires further investigation.

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