Norepinephrine-Induced DNA Damage in Ovarian Cancer Cells.

Multiple studies have shown that psychological distress in epithelial ovarian cancer (EOC) patients is associated with worse quality of life and poor treatment adherence. This may influence chemotherapy response and prognosis. Moreover, although stress hormones can reduce cisplatin efficacy in EOC treatment, their effect on the integrity of DNA remains poorly understood. In this study, we investigated whether norepinephrine and epinephrine can induce DNA damage and modulate cisplatin-induced DNA damage in three EOC cell lines. Our data show that norepinephrine and epinephrine exposure led to increased nuclear γ-H2AX foci formation in EOC cells, a marker of double-strand DNA breaks. We further characterized norepinephrine-induced DNA damage by subjecting EOC cells to alkaline and neutral comet assays. Norepinephrine exposure caused DNA double-strand breaks, but not single-strand breaks. Interestingly, pre-treatment with propranolol abrogated norepinephrine-induced DNA damage indicating that its effects may be mediated by ß-adrenergic receptors. Lastly, we determined the effects of norepinephrine on cisplatin-induced DNA damage. Our data suggest that norepinephrine reduced cisplatin-induced DNA damage in EOC cells and that this effect may be mediated independently of ß-adrenergic receptors. Taken together, these results suggest that stress hormones can affect DNA integrity and modulate cisplatin resistance in EOC cells.

Neuroendocrine Regulation of Tumor-Associated Immune Cells.

Mounting preclinical and clinical evidence continues to support a role for the neuroendocrine system in the modulation of tumor biology and progression. Several studies have shown data supporting a link between chronic stress and cancer progression. Dysregulation of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in promoting angiogenesis, tumor cell proliferation and survival, alteration of the immune response and exacerbating inflammatory networks in the tumor microenvironment. Here, we review how SNS and HPA dysregulation contributes to disturbances in immune cell populations, modifies cancer biology, and impacts immunotherapy response. We also highlight several interventions aimed at circumventing the adverse effects stress has on cancer patients.

Prevalence of breast and ovarian cancer subtypes in Hispanic populations from Puerto Rico.

BACKGROUND: Previous epidemiological studies aimed at describing characteristics of breast (BC) and ovarian cancer (OC) patients tend to examine Hispanic populations using a mix of individuals that come from ethnically different Hispanic backgrounds. Since most USA cancer statistics do not include cancer data from Puerto Rico (PR), there is a lack of historical and descriptive data analysis for Hispanic women in the island that suffer from these diseases. Therefore, the aim of our study is to provide a comprehensive clinicopathological characterization of BC and OC cases in PR. METHODS: Our study consisted of a longitudinal retrospective review of archived pathology reports at Southern Pathology Services (SPS), which mostly serves southwestern PR, from years 2000-2015. After filtering SPS records with pre-established criteria, tumor samples from 3451 BC and 170 OC cases were used for descriptive statistics and analysis using R program. RESULTS: In our cohort, the mean age of diagnosis for BC was 60.5 years and 60.3 years for OC. Available data for subtype characterization from BC cases, exhibited an expected subtype distribution that remained stable over time (Luminal A = 68.8%, Luminal B = 9.7%, HER-2 = 6.1% and Triple negative = 15.4%). Additionally, tumor grades distribution varied within different BC subtypes in which the majority of Luminal A tumors were G2 and most Triple negative tumors were G3. For OC cases, available subtype and tumor grade information identified serous histology in 64.71% of all cases and G3 as being the most prevalent tumor grade. Pathology reports revealed that 39.42% of all OC cases were described as late stage, while 50.5% as early stage (by pathological staging). CONCLUSION: Our data suggests that OC and BC subtypes distribution in Hispanic populations from PR are in-line with national averages. In a significant number of BC cases, subtype could not be determined due to study limitations, health insurance coverage, or other reasons described here and may constitute a health disparity. Altogether, and despite these gaps, this study represents one of the most complete reviews of BC and OC in PR and provides an opportunity to further study this population separate from other US Hispanic populations.