IntroductionTriple-negative breast cancer (TNBC) is an aggressive form of breast cancer with no effective targeted therapy. Inducible nitric oxide synthase (iNOS) is associated with poor survival in patients with breast cancer by increasing tumor aggressiveness. This work aimed to investigate the potential of iNOS inhibitors as a targeted therapy for TNBC. We hypothesized that inhibition of endogenous iNOS would decrease TNBC aggressiveness by reducing tumor initiation and metastasis through modulation of epithelial-mesenchymal transition (EMT)-inducing factors.MethodsiNOS protein levels were determined in 83 human TNBC tissues and correlated with clinical outcome. Proliferation, mammosphere-forming efficiency, migration, and EMT transcription factors were assessed in vitro after iNOS inhibition. Endogenous iNOS targeting was evaluated as a potential therapy in TNBC mouse models.ResultsHigh endogenous iNOS expression was associated with worse prognosis in patients with TNBC by gene expression as well as immunohistochemical analysis. Selective iNOS (1400 W) and pan-NOS (L-NMMA and L-NAME) inhibitors diminished cell proliferation, cancer stem cell self-renewal, and cell migration in vitro, together with inhibition of EMT transcription factors (Snail, Slug, Twist1, and Zeb1). Impairment of hypoxia-inducible factor 1α, endoplasmic reticulum stress (IRE1α/XBP1), and the crosstalk between activating transcription factor 3/activating transcription factor 4 and transforming growth factor β was observed. iNOS inhibition significantly reduced tumor growth, the number of lung metastases, tumor initiation, and self-renewal.ConclusionsConsidering the effectiveness of L-NMMA in decreasing tumor growth and enhancing survival rate in TNBC, we propose a targeted therapeutic clinical trial by re-purposing the pan-NOS inhibitor L-NMMA, which has been extensively investigated for cardiogenic shock as an anti-cancer therapeutic.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0527-x) contains supplementary material, which is available to authorized users.

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Introduction People with serious mental illness may be subjected to “court-ordered treatment” (COT), per the mental health statutes of their respective state. COT enforces adherence to a psychiatric treatment regimen and may involve involuntary medication administration. Long-acting injectable (LAI) antipsychotics are frequently used in this setting, although little is known about the clinical effectiveness or patterns of use of these agents in the context of COT. Because psychiatric pharmacists are medication experts, we sought to characterize their perceptions and experiences on this topic. Methods A cross-sectional, electronic, 14-item survey was administered via the College of Psychiatric and Neurologic Pharmacists listserv from October 9, 2018, to November 9, 2018. The survey collected demographic information, experience and use of LAI antipsychotics at each practice site, and perception of LAI antipsychotics. Results Of 843 possible respondents, 72 completed the survey, yielding an 8.5% response rate. LAIs were perceived as underused or adequately used as a whole, with a significant difference in perception favoring the opinion that LAIs are underused versus overused for those respondents who perceived an adherence benefit (P = .042). We also found that LAIs were used disproportionately in the context of COT versus oral formulations (P = .03). Discussion The use of LAIs in the context of COT has not been studied, and it may expose this vulnerable population to adverse effects from medications they are legally compelled to take. Further research on the perceptions of other interdisciplinary team members and the clinical impact of LAI use in COT is needed.

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Millions of consumers have chosen to pursue direct‐to‐consumer (DTC) genetic testing for personal health‐related and/or non‐health‐related information. However, genetic test results can be complex to interpret, and the regulatory landscape for DTC genetic tests is in flux. Given that these tests are easily accessible and may have implications for health, pharmacists need to be prepared to provide patient education on DTC genetic testing, particularly when the results may provide valuable insights into optimal pharmacotherapy. Pharmacists, regardless of practice site and specialty, are well positioned to provide patient education on the benefits, risks, and limitations of DTC pharmacogenomic tests in clinical practice and to advise patients about pursuing confirmatory clinical testing. This report highlights the responsibility of the pharmacist in the appropriate use of DTC genetic testing, particularly pharmacogenomic testing, using a patient case example across varied health settings.

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