Background: The Androgen Receptor (AR) nuclear transcription factor is a therapeutic target for prostate cancer (PCa). Unfortunately, patients can develop resistance to AR-targeted therapies and progress to lethal disease, underscoring the importance of understanding the molecular mechanisms that underlie treatment resistance. Inflammation is implicated in PCa initiation and progression and we have previously reported that the inflammatory cytokine, . CC-BY-NC-ND 4.

SARS-CoV-2 is a novel virus that has resulted in a global pandemic since the first cases were reported in late 2019 from Wuhan, China. It is also a coronavirus that shares similarities to SARS-CoV and MERS-CoV with respect to pathophysiology, transmission, and affected populations. A review of the literature was conducted to explain possible underlying reasons for the difference in coronaviruses’ effects on certain demographics with a focus on gender/sex and race/ethnicity. Both male and female genders vary in their biological makeup, including immunity, hormones, and physiological components, such as angiotensin-converting enzyme 2 (ACE2). These variations seem to give moderate support to the data that demonstrate a higher mortality rate of COVID-19 in males. Yet, these factors must be investigated further since the current studies are limited in scope and sample size as the COVID-19 pandemic continues to evolve. Information involving COVID-19 racial and ethnic data currently is limited, as most countries have not recorded cases based on race or ethnicity, but primarily age and gender. The United States Centers for Disease Control and Prevention (CDC) limited data have shown that racial minorities, such as African-Americans, are more likely to have worse outcomes. This could be due to other parameters, including healthcare disparities, biological factors, and socioeconomic status. Further research in understanding both gender/sex and race/ethnicity with respect to respiratory viruses, including COVID-19, could potentially improve the poor prognosis seen among particular demographics.

Purpose The negative correlation between BPH-size and incidence of prostate cancer (PCa) is well-documented in the literature, however the exact mechanism is not well-understood. The present study uses histo-anatomical imaging to study prostate volume in correlation to prostate capsule thickness, and glandular epithelial cell density within the peripheral zone (PZ). Materials and Methods Specimens were selected from radical prostatectomies ranging from 20 to 160 mL based on ease of anatomical reconstruction by the slides. A total of 60 patients were selected and underwent quantitative measurements of prostate capsule thickness and glandular epithelial density within the PZ using computer-based imaging software. Pearson's correlation and a stepwise multiple linear regression analysis was conducted to determine the relationship between these measured parameters and the clinical characteristic of these patients. Results Pearson's correlation analysis revealed a strongly significant, negative correlation between prostate volume and glandular epithelial cell density (r(58)=−0.554, p<0.001), and a strongly significant, positive correlation between prostate volume and average capsule thickness (r(58)=0.462, p<0.001). Results of multiple regression analysis showed that average glandular epithelial cell density added statistically to this prediction (p<0.05). Conclusions The results suggest that growth of the transition zone in BPH causes increased fibrosis of the PZ, leading to atrophy and fibrosis of glandular cells. As 80% of PCa originates from the glandular epithelium within the PZ, this observed phenomenon may explain the inverse correlation between BPH and PCa that is well-documented in the literature.

Inflammation promotes cancer initiation and progression. The Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B cells (NF-κB) family of transcription factor proteins, p65 (RelA), RelB, c-Rel, p105/p50 (NF-κB1), and p100/52 (NF-κB2), form homo- and heterodimeric complexes that mediate inflammatory cytokine signaling. We previously reported that the inflammatory cytokines, interleukin-1 alpha (IL-1α) and IL-1 beta (IL-1β), repress androgen receptor (AR) levels and activity in AR+ prostate cancer (PCa) cell lines. AR drives PCa tumorigenicity and, thus, AR is a therapeutic target. Our data suggests that IL-1 selects for ARlow/-PCa cell subpopulations that can evade AR-targeting therapy. Using RNA sequencing, we identified an IL-1-regulated gene signature predicted to supported AR-independent tumorigenicity in PCa cells. Pathway analysis of the RNA sequencing data predicted that AR is a target molecule of p65 (RELA). p50:p65 heterodimers are known to mediate IL-1 signaling, therefore, we investigated if NF-κB (p50:p65) signaling mediates IL-1 repression of AR. We found that siRNA silencing of p65 is sufficient to attenuate IL-1 repression of AR mRNA and protein levels and AR activity in AR+ PCa cell lines, while siRNA silencing of p50 had no effect on IL-1 repression of AR. Our data suggests that p65 represses AR levels, directly or indirectly, in response to IL-1. Thus, therapeutic inhibition of p65 activity could prevent the accumulation of inflammation-induced treatment-resistance ARlow/- PCa cell subpopulations. Citation Format: Shayna Elizabeth Thomas-Jardin, Haley Dahl, Monica Bautista, Freedom Ha, Joan Jacob, Afshan Fathima Nawas, Mohammed Kanshwala, Chao Xing, Nikki Delk. NF-κB (p65) mediates interleukin-1 (IL-1) repression of androgen receptor (AR) in AR+prostate cancer (PCa) cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2362.