Screening of GPCR drugs for repurposing in breast cancer.

Drug repurposing can overcome both substantial costs and the lengthy process of new drug discovery and development in cancer treatment. Some Food and Drug Administration (FDA)-approved drugs have been found to have the potential to be repurposed as anti-cancer drugs. However, the progress is slow due to only a handful of strategies employed to identify drugs with repurposing potential. In this study, we evaluated GPCR-targeting drugs by high throughput screening (HTS) for their repurposing potential in triple-negative breast cancer (TNBC) and drug-resistant human epidermal growth factor receptor-2-positive (HER2+) breast cancer (BC), due to the dire need to discover novel targets and drugs in these subtypes. We assessed the efficacy and potency of drugs/compounds targeting different GPCRs for the growth rate inhibition in the following models: two TNBC cell lines (MDA-MB-231 and MDA-MB-468) and two HER2+ BC cell lines (BT474 and SKBR3), sensitive or resistant to lapatinib + trastuzumab, an effective combination of HER2-targeting therapies. We identified six drugs/compounds as potential hits, of which 4 were FDA-approved drugs. We focused on ß-adrenergic receptor-targeting nebivolol as a candidate, primarily because of the potential role of these receptors in BC and its excellent long-term safety profile. The effects of nebivolol were validated in an independent assay in all the cell line models. The effects of nebivolol were independent of its activation of ß3 receptors and nitric oxide production. Nebivolol reduced invasion and migration potentials which also suggests its inhibitory role in metastasis. Analysis of the Surveillance, Epidemiology and End Results (SEER)-Medicare dataset found numerically but not statistically significant reduced risk of all-cause mortality in the nebivolol group. In-depth future analyses, including detailed in vivo studies and real-world data analysis with more patients, are needed to further investigate the potential of nebivolol as a repurposed therapy for BC.

A Pilot Study of a Top-Tier Contraception Simulation Program to Improve Long-Acting Reversible Contraception Practices Among Health Care Trainees.

BACKGROUND AND OBJECTIVES: Long-acting reversible contraception methods are effective tools in family planning. However, resident physicians and other health care trainees may experience knowledge gaps and low utilization because of limited opportunity for training. The purpose of this pilot study is to evaluate self-assessed knowledge, counseling, and long-acting reversible contraception (LARC) device placement skills among health care trainees who attended a 1-day simulation-based training. In addition, we describe a simulation-based training program we developed to facilitate the use of LARC among health professionals. METHODS: We conducted a cross-sectional evaluation of health care trainees attending simulation-based training on 2 occasions in 2017 and one occasion in 2018 in Chicago, Illinois. Participants rated their experience, comfort providing counseling, and placement skills with all LARC methods. Knowledge was measured using a series of multiple-choice questions. Responses to the survey were summarized using frequencies and percentages. RESULTS: A total of 253 health care professionals attended the simulations, and 244 completed the presurvey (96.4% response rate). Of those, 172 respondents were health care trainees, of which a majority were resident physicians. More than half reported never using top-tier methods in practice. Most indicated moderate to low knowledge to counsel patients and low skills to place each of the devices before training; self-reported knowledge and skills increased after completing training. Presimulation knowledge scores ranged from 0 to 19, with a median score of 14 of 19 correct responses. After training, average scores increased by 3 points (P < 0.0001). CONCLUSIONS: One-day training events can provide didactic education and simulation-based skills training in device placement that may result in increased access among the patients served by these providers.

The Cervical Dysplasia Worksheet: A Longitudinal Map of Cervical Dysplasia Cytology and Histology Tests and Procedures.

OBJECTIVE: Our objectives were to describe the Cervical Dysplasia Worksheet (CDW), provide evidence of its feasibility to view patient cervical dysplasia results over time, and evaluate patient attitudes toward the tool in the setting of abnormal result follow-up. MATERIALS AND METHODS: The CDW augments the ASCCP guidelines for managing abnormal cervical cancer screenings by visually depicting cervical cytological and histological history along a color gradient showing severity. We evaluated tool feasibility by graphing a retrospectively reviewed convenience sample of patient data. A cross-sectional evaluation of the tool was then performed to assess patient attitudes in the setting of either dysplasia or colposcopy clinic. Patients had their data graphed on the CDW and explained to them before their clinical encounter. They then gave general comments about the tool and filled out a short evaluation survey. RESULTS: The large majority of retrospective patient data (N = 167) fit well within the CDW with roughly 20% requiring space for additional comments. Among the 30 patients who participated in our evaluation, almost all agreed (n = 29, 96.7%) that the tool helped them understand their history and results and that they would use the tool in the future. CONCLUSIONS: The CDW is a novel tool to display a patient's cervical dysplasia history to visualize treatment and future care while enhancing patient-provider communication. Patient evaluation of the tool was largely positive, and suggestions will be taken into consideration for future modification. Further evaluation of the CDW among healthcare providers is needed to analyze its efficacy in the clinical setting.

Using Peer Health Educators to Conduct Community Level Surveillance of HPV Vaccination Status: Findings Among Women Who Live in Medically Underserved Areas of Chicago.

Young women are key stakeholders in efforts to increase human papillomavirus (HPV) vaccination uptake. Community health workers who engage with young women can provide valuable information to inform intervention strategies to increase vaccine uptake. We aimed to determine HPV vaccination and sexually transmitted infection (STI) rates among urban women and to identify barriers to vaccination. A trained health educator collaborated with community-based organizations to host health education and STI testing sessions for women in Chicago, Illinois. Forty-nine sessions took place at 15 sites over two years. Each attendee met with the educator about sexual health and HPV vaccination, and completed a health survey. We used contingency tables and logistic regression to determine factors associated with HPV vaccination using the cross-sectional survey data. Of the 292 women who answered questions about history of HPV vaccination, the average age was 17 (SD 2.3) years old, 63% (n = 184) were African American, and 33% (n = 98) Hispanic. Only 13.4% (n = 39) previously received the vaccine, and 6.2% (n = 18) received two to three doses. After adjustment, prior HIV testing was associated with 4.6 times higher odds (95% CI 1.71, 12.53, p = 0.002) of being vaccinated compared to women without prior testing. Our study provides evidence that young African American and Hispanic women living in Chicago may have low HPV vaccination rates. Women who received prior STI testing (i.e., sought healthcare) were more likely to be vaccinated relative to their peers who did not, indicating that racial/ethnic or socioeconomic disparities may inhibit utilization of preventative services.