RESUMEN
Objectives: To evaluate the performance of measurement of glomerular filtration rate (GFR) using Modification of Diet in Renal Disease equations (MDRD186, MDRD175) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, in comparison with technetium-99m diethylenetriaminepentaacetic acid (99Tc-DTPA) renogram method, the gold standard. A related aim was to correlate the three equations to estimate GFR and their impact on reclassifying the stages of CKD in adult Omani patients. Methods: This cross-sectional study recruited two groups of patients diagnosed with CKD during a 10-month period from January to October 2021. The first group comprised 48 patients who underwent a 99Tc-DTPA renogram procedure for GFR measurement, and the second group comprised 30 348 adult patients who did not undergo the same procedure; estimated GFR was calculated using the three equations. Results: The median of the reference GFR was 106.0 mL/min/1.73 m2, whereas the median estimated GFR for the MDRD175, MDRD186, and CKD-EPI equations were 92.5, 98.3, and 102.1, respectively. All three equations correlated moderately with the reference GFR (0.428, 0.428, 0.523, respectively; p < 0.010). The CKD-EPI showed lesser bias (3.7 vs. 12.9 and 7.5 for MDRD175 and MDRD186, respectively) and more accuracy (95.8% vs. 91.7% and 93.8%); however, it was the least precise (25.1 vs. 22.3 and 23.8). The MDRD186 performed similarly to the CKD-EPI equation at CKD stages 3a-5 and differed significantly at stages 1-2. Whereas the MDRD175 differed significantly with both equations at stages 1-3b and was similar to them at stages 4-5. Conclusions: The CKD-EPI equation had the highest accuracy and the least bias and precision in the general population. The MDRD186 CKD classification differed significantly from the CKD-EPI equation at CKD-stages 1-2 only. The CKD-EPI equation is preferred to MDRD for the detection and classification of early CKD stages.
RESUMEN
Fatty acid synthase (FASN) is a key enzyme in fat biosynthesis that is over-expressed in advanced breast cancer stages. Cisplatin (CDDP) is a platinum-based drug used in the treatment of certain types of this disease. Although it was shown that FASN inhibition induced apoptosis by enhancing the cytotoxicity of certain drugs in breast cancer, its role in regulating the chemosensitivity of different types of breast cancer cells to CDDP-induced apoptosis is not established yet. Therefore, two different breast cancer cell lines; triple negative breast cancer (TNBC; MDA-MB-231) and triple positive breast cancer (TPBC; BT-474) cells were used to examine such role. We show that TNBC cells had naturally less fat content than TPBC cells. Subsequently, the fat content increased in both cells when treated with Palmitate rather than Oleate, whereas both fatty acids produced apoptotic ultra-structural effects and attenuated FASN expression. However, Oleate increased FASN expression in TPBC cells. CDDP decreased FASN expression and increased apoptosis in TNBC cells. These effects were further enhanced by combining CDDP with fatty acids. We also illustrate that the inhibition of FASN by either siRNA or exogenous inhibitor decreased CDDP-induced apoptosis in TPBC cells suggesting its role as an apoptotic factor, while an opposite finding was observed in TNBC cells when siRNA and fatty acids were used, suggesting its role as a survival factor. To our knowledge, we are the first to demonstrate a dual role of FASN in CDDP-induced apoptosis in breast cancer cells and how it can modulate their chemosensitivity.