Racial and Ethnic Trends in Prostate Cancer Incidence and Mortality in Philadelphia, PA: an Observational Study.

BACKGROUND: To learn more about local prostate cancer (PCa) disparities, we conducted descriptive analyses of the role of race and age in PCa using the Pennsylvania Cancer Registry data for Philadelphia (2005-2014). METHODS: We focused on the most prevalent race/ethnic groups: white (33%), black (44%), and Hispanic (9%). Outcomes included PCa rates, tumor stage, and tumor grade. Percent change was used to describe changes in age-adjusted incidence and mortality rates. Frequency tables and logistic regression models were used to describe trends in proportions of advanced PCa by race and time. Race-by-time interaction terms were retained in the models if statistically significant. RESULTS: PCa incidence was highest for black men over time. Incidence rates declined over time for all race groups (- 28% for white men to - 38% for Hispanic men). PCa mortality rates declined in a less universal manner (- 5% for blacks to - 32% for whites). Each year, odds increased across all race groups for advanced tumor stage (4% each year among white and Hispanic men and 9% each year among black men) and for advanced tumor grade (4% each year among white and black men and 23% each year among Hispanic men). Among younger men, black men experienced significantly increased odds of advanced tumor stage each year (8%) and Hispanics experienced significantly increased odds of advanced tumor grade each year (30%). CONCLUSIONS: Black men remain at highest PCa risk relative to other racial/ethnic groups in Philadelphia. Younger black and Hispanic men are at particular risk for advanced PCa at diagnosis.

Novel Imidazopyridine Derivatives Possess Anti-Tumor Effect on Human Castration-Resistant Prostate Cancer Cells.

Prostate cancer (PCa) is the second leading cause of cancer-related death afflicting United States males. Most treatments to-date for metastatic PCa include androgen-deprivation therapy and second-generation anti-androgens such as abiraterone acetate and enzalutamide. However, a majority of patients eventually develop resistance to these therapies and relapse into the lethal, castration-resistant form of PCa to which no adequate treatment option remains. Hence, there is an immediate need to develop effective therapeutic agents toward this patient population. Imidazopyridines have recently been shown to possess Akt kinase inhibitory activity; thus in this study, we investigated the inhibitory effect of novel imidazopyridine derivatives HIMP, M-MeI, OMP, and EtOP on different human castration-resistant PCa cells. Among these compounds, HIMP and M-MeI were found to possess selective dose- and time-dependent growth inhibition: they reduced castration-resistant PCa cell proliferation and spared benign prostate epithelial cells. Using LNCaP C-81 cells as the model system, these compounds also reduced colony formation as well as cell adhesion and migration, and M-MeI was the most potent in all studies. Further investigation revealed that while HIMP primarily inhibits PCa cell growth via suppression of PI3K/Akt signaling pathway, M-MeI can inhibit both PI3K/Akt and androgen receptor pathways and arrest cell growth in the G2 phase. Thus, our results indicate the novel compound M-MeI to be a promising candidate for castration-resistant PCa therapy, and future studies investigating the mechanism of imidazopyridine inhibition may aid to the development of effective anti-PCa agents.