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Breast cancer, as the most prevalent cancer in women, is responsible for more than 15% of new cancer cases and about 6.9% of all cancer-related death in the US. A major cause of therapeutic failure in breast cancer is the development of resistance to chemotherapy, especially for triple-negative breast cancer (TNBC). Therefore, how to overcome chemoresistance is the major challenge to improve the life expectancy of breast cancer patients. Our studies demonstrate that TNBC cells surviving the chronic treatment of chemotherapeutic drugs show significantly higher expression of the dual serine/threonine and tyrosine protein kinase (DSTYK) than non-treated parental cells. In our in vitro cellular models, DSTYK knockout via the CRISPR/Cas9-mediated technique results in apoptotic cell death of chemoresistant cells upon drug treatment. Moreover, DSTYK knockout promotes chemotherapeutic drug-induced tumor cell death in an orthotopic mouse model. These findings suggest that DSTYK exerts an important and previously unknown role in promoting chemoresistance. Our studies provide fundamental insight into the role of DSTYK in chemoresistance in TNBC cells and lay the foundation for the development of new strategies targeting DSTYK for improving TNBC therapy. [ABSTRACT FROM AUTHOR]

Background/objectives : The association between adverse childhood experiences (ACEs) and asthma severity among United States (US) adults with asthma has not been well documented. In addition, whether gender differences exist in this association has been underexplored. We aimed to examine the prevalence of asthma severity in the US adult population with asthma and investigate the association between ACEs and asthma severity by using data from non-institutionalized US adults with asthma. Methods : This cross-sectional study used data from the Adult 2019 and 2020 Behavioral Risk Factor Surveillance System (BRFSS) Asthma Call-Back Survey (ACBS), a survey of US adults aged 18 years or older in 31 US states and Puerto Rico. A total of 22934 adults with asthma participated in 2019 and 2020 ACBS. The 11 BRFSS ACE variables encompassing abuse and household dysfunction were used as ACE measures. ACE measures were summed up as cumulative ACE scores (continuous) and categorized (zero, one ACE, two ACEs, ≥ three ACEs). Asthma severity was categorized as intermittent or persistent. Weighted logistic regression models were used to assess associations of the cumulative ACE score, categorical ACE measures, and the 11 individual ACE responses with asthma severity controlling confounders. Gender differences were explored by stratifying by gender. Results: The prevalence of persistent asthma among US adults with asthma was 45.3%. The mean cumulative ACE score in adults with intermittent vs. persistent asthma was (2.43 vs. 2.70, p -value < 0.05). About 22% of adults with asthma had no ACEs, 19% had one ACE, 14% had two ACEs, and 45% had three or more ACEs. A one-unit increase in ACEs score was associated with a 5.4% increase in the odds of persistent asthma (adjusted odds ratio, aOR = 1.054 (95% confidence interval, CI = 1.01-1.10). Experiencing ≥ three ACEs compared to no ACEs was associated with 31% increased odds of persistent asthma (aOR = 1.31, 95% CI = 1.01-1.70). Individual ACE items significantly associated with persistent asthma include parent/adult ever touched you sexually (aOR = 1.33, 95% CI = 1.03-1.74), adult tried to make you touch them (aOR = 1.34, 95% CI = 1.01-1.79), any adult forced you to have sex (aOR = 1.44, 95% CI = 1.04-1.20), parental separation/divorce (aOR = 1.31, 95% CI = 1.05-1.63), and household alcohol abuse (aOR = 1.24, 95% CI = 1.01-1.53). In women, experiencing one ACE and ≥ three ACEs (compared to no ACEs) was associated with 51% and 60% increased odds of persistent asthma, respectively (aOR = 1.51, 95% CI = 1.02-2.23; aOR = 1.60, 95% CI = 1.12-2.27). No significant association was observed between ACEs and asthma severity in men; however, experiencing household physical violence (compared to no household physical violence) was associated with persistent asthma in men (aOR = 1.69, 95% CI = 1.18-2.42). Conclusions : In this cross-sectional study of US adults with asthma, exposure to ACEs was associated with higher odds of asthma overall and in women. These findings highlight the importance of preventive strategies and early interventions to reduce ACEs, potentially mitigating asthma's severity in adulthood.