The effect of HIF-1α inhibition in breast cancer cells prior to doxorubicin treatment under conditions of normoxia and hypoxia.

BACKGROUND: Oxygen deprivation is a key hallmark within solid tumours that contributes to breast-tumour pathophysiology. Under these conditions, neoplastic cells activate several genes, regulated by the HIF-1 transcription factor, which alters the tumour microenvironment to promote survival - including resistance to cell death in therapeutic attempts such as doxorubicin (Dox) treatment. METHODS: We investigated HIF-1ɑ as a therapeutic target to sensitize breast cancer cells to Dox treatment. Under both normoxic (21% O2) and hypoxic (∼0.1% O2) conditions, the HIF-1 inhibitor, 2-methoxyestradiol (2-ME), was investigated as an adjuvant for its ability to alter MCF-7 cell viability, apoptosis, autophagy and molecular pathways which are often associated with increased cell survival. RESULTS: Here we observed that an inverse relationship between HIF-1ɑ and apoptosis exists and that Dox promotes autophagy under hypoxic conditions. Although adjuvant therapy with 2-ME induced an antagonistic effect in breast cancer cells, upregulated HIF-1ɑ expression in a hypoxic environment promotes treatment resistance and this was attenuated once HIF-1ɑ gene expression was silenced. CONCLUSION: Therefore, highlighting the identification of possible hypoxia-targeting therapies for breast cancer patients can be beneficial by promoting more favourable treatment responses.

Prevalence of Metachronous Advanced Colorectal Neoplasia in Black and White Patients at a Safety Net Hospital.

Background and Aims: Current postpolypectomy surveillance guidelines are based primarily on data from non-Hispanic Whites (NHWs); thus, generalizability to non-Hispanic Blacks (NHBs) remains unknown. Hence, the primary objective of this study was to assess the validity of these guidelines for NHBs by comparing the prevalence of metachronous advanced colorectal neoplasia (ACN) between NHWs and NHBs undergoing surveillance colonoscopy. Methods: This was a retrospective cross-sectional study of NHWs (N = 1500) and NHBs (N = 1260) aged 40-75 years who underwent surveillance colonoscopy at an academic safety net hospital between 2007 and 2017. The primary outcome measure was the prevalence of metachronous ACN, defined as an advanced adenoma, advanced sessile polyp, or invasive cancer. Multivariate logistic regression was used to measure associations between race/ethnicity and ACN prevalence after adjustment for potential confounding factors. Results: Overall, the prevalence of metachronous ACN was similar for NHBs and NHWs (6.8% vs 7.4%, respectively; P = .60). The prevalence of metachronous cancers (0.2% vs 0.1%; P = .48), advanced adenomas (2.8% vs 3.8%; P = .14), advanced serrated polyps (3.5% vs 3.3%; P = .82), and large hyperplastic polyps ≥10 mm (0.2% vs 0.6%, P = .24) were also similar between the 2 groups. Moreover, race was not a determinant of metachronous ACN after adjustment for age, sex, education, type of insurance, indication (screen/surveillance) for baseline colonoscopy, surveillance interval, and findings at baseline colonoscopy (adjusted odds ratio, 0.96; 95% confidence interval, 0.70-1.30; P = .78). Conclusion: Our study finds no significant difference in the prevalence of metachronous ACN between NHWs and NHBs undergoing appropriate postpolypectomy surveillance at an urban safety net hospital, suggesting that current guidelines are appropriate for both NHWs and NHBs.

Developing Primary Care-Based Recommendations for Social Determinants of Health: Methods of the U.S. Preventive Services Task Force.

The purpose of the U.S. Preventive Services Task Force (USPSTF) is to provide evidence-based recommendations on primary care screening, behavioral counseling, and preventive medications. A person's health is strongly influenced by social determinants of health, such as economic and social conditions; therefore, preventive recommendations that address these determinants would be ideal. However, differing social determinants have been proposed by a wide range of agencies and organizations, little prevention evidence is available, and responsible parties are in competition, all of which make the creation of evidence-based prevention recommendations for social determinants of health challenging. This article highlights social determinants already included in USPSTF recommendations and proposes a process by which others may be considered for primary care preventive recommendations. In many ways, incorporating social determinants of health into evidence-based recommendations is an evolving area. By reviewing the evidence on the effects of screening and interventions on social determinants relevant to primary care, the USPSTF will continue to provide recommendations on clinical preventive services to improve the health of all Americans.