ABSTRACT
Background: Tamoxifen is commonly used in the treatment of hormonal-positive breast cancer. However, 30%-40% of tumors treated with tamoxifen develop resistance; therefore, an important step to overcome this resistance is to understand the underlying molecular and metabolic mechanisms. In the present work, we used metabolic profiling to determine potential biomarkers of tamoxifen resistance, and gene expression levels of enzymes important to these metabolites and then correlated the expression to the survival of patients receiving tamoxifen. Methods: Tamoxifen-resistant cell lines previously developed and characterized in our laboratory were metabolically profiled with nuclear magnetic resonance spectroscopy (NMR) using cryogenic probe, and the findings were correlated with the expression of genes that encode the key enzymes of the significant metabolites. Moreover, the effect of significantly altered genes on the overall survival of patients was assessed using the Kaplan-Meier plotter web tool. Results: We observed a significant increase in the levels of glutamine, taurine, glutathione, and xanthine, and a significant decrease in the branched-chain amino acids, valine, and isoleucine, as well as glutamate and cysteine in the tamoxifen-resistant cells compared to tamoxifen sensitive cells. Moreover, xanthine dehydrogenase and glutathione synthase gene expression were downregulated, whereas glucose-6-phosphate dehydrogenase was upregulated compared to control. Additionally, increased expression of xanthine dehydrogenase was associated with a better outcome for breast cancer patients. Conclusion: Overall, this study sheds light on metabolic pathways that are dysregulated in tamoxifen-resistant cell lines and the potential role of each of these pathways in the development of resistance.
ABSTRACT
BACKGROUND: Glaucoma is considered the second most common cause of blindness in patients above the age of 50. Lack of adherence to glaucoma medications frequently results in undesirable complications, specifically blindness and disability. PURPOSE: The study's objectives are to evaluate the level of adherence to glaucoma topical medications and factors associated with adherence to glaucoma medications. PATIENTS AND METHODS: In total, 348 patients, of whom 48.6% were above the age of 65, were recruited. A cross-sectional study from August 2018 to March 2020 was conducted on glaucoma patients who were referred to the Department of Ophthalmology in Royal Medical Services in Amman, Jordan. A questionnaire was employed to collect patients' demographic data, level of adherence, and factors associated with medication adherence. The inclusion criteria include the following: age above 20 years, diagnosis of glaucoma, currently under medical treatment, and willingness to participate in the study. Exclusion criteria include the following: patients who were hospitalized for glaucoma treatment, patients who had unstable medical conditions, and any patients for whom ophthalmologists had determined that they should be excluded for any other reasons. RESULTS: Almost half (47.1%) of the patients adhered to their personal glaucoma medications, and the most frequent cause of nonadherence was forgetfulness (39.9%), whereas the least common was stopping the drug after feeling better (7.0%). CONCLUSION: Proper patient education and explanation of the seriousness of medication adherence and its association with treatment outcomes, along with assisting old and disabled patients when applying ophthalmic medications, may positively improve the adherence of patients to glaucoma and other related visual impairment medications.