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#33979195   // To Up

Evolution of Disparities in Prostate Cancer Treatment: Is This a New Normal?

Despite notable screening, diagnostic, and therapeutic advances, disparities in prostate cancer incidence and outcomes remain prevalent. Although commonly discussed in the context of men of African descent, disparities also exist based on socioeconomic level, education level, and geographic location. The factors in these disparities span systemic access issues affecting availability of care, provider awareness, and personal patient views and mistrust. In this review, we will discuss common themes that patients have noted as impediments to care. We will review how equitable access to care has helped improve outcomes among many different groups of patients, including those with local disease and those with metastatic castration-resistant prostate cancer. Even with more advanced presentation, challenges with recommended screening, and lower rates of genomic testing and trial inclusion, Black populations have benefited greatly from various modalities of therapy, achieving comparable and at times superior outcomes with certain types of immunotherapy, chemotherapy, androgen receptor-based inhibitors, and radiopharmaceuticals in advanced disease. We will also briefly discuss access to genomic testing and differences in patterns of gene expression among Black patients and other groups that are traditionally underrepresented in trials and genomic cohort studies. We propose several strategies on behalf of providers and institutions to help promote more equitable care access environments and continued decreases in prostate cancer disparities across many subgroups.
Frank C Cackowski, Brandon Mahal, Elisabeth I Heath, Bradley Carthon

2715 related Products with: Evolution of Disparities in Prostate Cancer Treatment: Is This a New Normal?



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#33977248   2021/03/22 To Up

Transcription factor 4 expression in circulating tumor cells from castration-resistant prostate cancer.

Neuroendocrine differentiation is partly caused by antiandrogen therapy and exhibits an androgen receptor-independent growth mechanism. We hypothesized that the expression of transcription factor 4, an inducer of neuroendocrine differentiation, in circulating tumor cells is related to drug resistance in castration-resistant prostate cancer.
Naoya Nagaya, Geun Taek Lee, Yan Lu, Takeshi Ashizawa, Masayoshi Nagata, Isaac Yi Kim, Shigeo Horie

1401 related Products with: Transcription factor 4 expression in circulating tumor cells from castration-resistant prostate cancer.

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#33976187   2021/05/11 To Up

Androgen signaling uses a writer and a reader of ADP-ribosylation to regulate protein complex assembly.

Androgen signaling through the androgen receptor (AR) directs gene expression in both normal and prostate cancer cells. Androgen regulates multiple aspects of the AR life cycle, including its localization and post-translational modification, but understanding how modifications are read and integrated with AR activity has been difficult. Here, we show that ADP-ribosylation regulates AR through a nuclear pathway mediated by Parp7. We show that Parp7 mono-ADP-ribosylates agonist-bound AR, and that ADP-ribosyl-cysteines within the N-terminal domain mediate recruitment of the E3 ligase Dtx3L/Parp9. Molecular recognition of ADP-ribosyl-cysteine is provided by tandem macrodomains in Parp9, and Dtx3L/Parp9 modulates expression of a subset of AR-regulated genes. Parp7, ADP-ribosylation of AR, and AR-Dtx3L/Parp9 complex assembly are inhibited by Olaparib, a compound used clinically to inhibit poly-ADP-ribosyltransferases Parp1/2. Our study reveals the components of an androgen signaling axis that uses a writer and reader of ADP-ribosylation to regulate protein-protein interactions and AR activity.
Chun-Song Yang, Kasey Jividen, Teddy Kamata, Natalia Dworak, Luke Oostdyk, Bartlomiej Remlein, Yasin Pourfarjam, In-Kwon Kim, Kang-Ping Du, Tarek Abbas, Nicholas E Sherman, David Wotton, Bryce M Paschal

1211 related Products with: Androgen signaling uses a writer and a reader of ADP-ribosylation to regulate protein complex assembly.

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#33975627   2021/05/11 To Up

Functional mapping of androgen receptor enhancer activity.

Androgen receptor (AR) is critical to the initiation, growth, and progression of prostate cancer. Once activated, the AR binds to cis-regulatory enhancer elements on DNA that drive gene expression. Yet, there are 10-100× more binding sites than differentially expressed genes. It is unclear how or if these excess binding sites impact gene transcription.
Chia-Chi Flora Huang, Shreyas Lingadahalli, Tunc Morova, Dogancan Ozturan, Eugene Hu, Ivan Pak Lok Yu, Simon Linder, Marlous Hoogstraat, Suzan Stelloo, Funda Sar, Henk van der Poel, Umut Berkay Altintas, Mohammadali Saffarzadeh, Stephane Le Bihan, Brian McConeghy, Bengul Gokbayrak, Felix Y Feng, Martin E Gleave, Andries M Bergman, Colin Collins, Faraz Hach, Wilbert Zwart, Eldon Emberly, Nathan A Lack

2698 related Products with: Functional mapping of androgen receptor enhancer activity.

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#33974920   2021/05/08 To Up

Androgen and Glucocorticoid Receptor Phosphorylation Following Resistance Exercise and Pre-Workout Supplementation.

Consumption of caffeine or caffeine containing pre-workout supplements (SUPP) augments steroid hormone responses to resistance exercise (RE). However, the activation of glucocorticoid (GR) and androgen receptors (AR) following RE SUPP has not been investigated. The purpose of this study was to determine the influence of a pre-workout supplement on AR and GR phosphorylation following RE.
Justin X Nicoll, Andrew C Fry, Eric M Mosier

1648 related Products with: Androgen and Glucocorticoid Receptor Phosphorylation Following Resistance Exercise and Pre-Workout Supplementation.

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#33974127   2021/05/11 To Up

Cytoplasmic DDX3 as prognosticator in male breast cancer.

Male breast cancer (MBC) is a rare disease. Due to its rarity, treatment is still directed by data mainly extrapolated from female breast cancer (FBC) treatment, despite the fact that it has recently become clear that MBC has its own molecular characteristics. DDX3 is a RNA helicase with tumor suppressor and oncogenic potential that was described as a prognosticator in FBC and can be targeted by small molecule inhibitors of DDX3. The aim of this study was to evaluate if DDX3 is a useful prognosticator for MBC patients. Nuclear as well as cytoplasmic DDX3 expression was studied by immunohistochemistry in a Dutch retrospective cohort of 106 MBC patients. Differences in 10-year survival by DDX3 expression were analyzed using log-rank test. The association between clinicopathologic variables, DDX3 expression, and survival was tested in uni- and multivariate Cox-regression analysis. High cytoplasmic DDX3 was associated with high androgen receptor (AR) expression while low nuclear DDX3 was associated with negative lymph node status. Nuclear and cytoplasmic DDX3 were not associated with each other. In a univariate analysis, high cytoplasmic DDX3 (p = 0.045) was significantly associated with better 10-year overall survival. In multivariate analyses, cytoplasmic DDX3 had independent prognostic value (p = 0.017). In conclusion, cytoplasmic DDX3 expression seems to be a useful prognosticator in MBC, as high cytoplasmic DDX3 indicated better 10-year survival.
Carmen C van der Pol, Cathy B Moelans, Quirine F Manson, Marilot C T Batenburg, Elsken van der Wall, Inne Borel Rinkes, Lenny Verkooijen, Venu Raman, Paul J van Diest

2913 related Products with: Cytoplasmic DDX3 as prognosticator in male breast cancer.



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#33973822   2021/05/11 To Up

Anabolic steroid misuse and male infertility: management and strategies to improve patient awareness.

: Anabolic androgenic steroid use is an uncommon but important cause of male infertility. As paternal age and anabolic steroid use increases, providers are more likely than ever to encounter men with infertility and prior or concurrent anabolic steroid use. In this review, we outline the background, epidemiology and pathophysiology of anabolic steroid induced male infertility and provide recommendations regarding the diagnosis, management, and future prevention of this condition.: Male reproductive physiology is a tightly regulated process that can be influenced by exogenous sources such as anabolic steroids and selective androgen receptor modulators (SARMs). Data suggest that a combination of selective estrogen receptor modulators (SERMs), human chorionic gonadotropin (hCG), aromatase inhibitors (AIs), and recombinant follicle-stimulating hormone (rFSH) may lead to spermatogenesis recovery.: Anabolic steroid and SARM users continue to exhibit lack of understanding regarding the potential side effects of their use on male fertility. Current literature suggests that spermatogenesis can be safely recovered using a combination of SERMs, hCG, AIs and rFSH although additional studies are necessary. While anabolic steroid prevention strategies have largely been focused on the individual level, further investigation is necessary and should be approached in a socioecological manner.
Dustin L Whitaker, Gabriella Geyer-Kim, Edward D Kim

1279 related Products with: Anabolic steroid misuse and male infertility: management and strategies to improve patient awareness.

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