Renal cell carcinoma (RCC) is usually chemoresistant. This chemoresistance could be overcome if specific cytostatics are applied for which the RCC expresses an uptake transporter. In the present study, we investigated the expression of solute carrier (SLC) transporters in different RCC lines and their ability to interact with chemotherapeutics. We tested five RCC lines for the expression of different SLCs by reverse transcription-PCR and TaqMan real-time PCR. In two of five RCC lines, A498 and 7860, we observed a highly significant expression of SLC22A3 (hOCT3 ]thymidine incorporation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays on CHO-hOCT3, A498 (high expression of hOCT3), and ACHN cell lines (low expression of hOCT3). The growth of CHO-hOCT3 was inhibited by 20% more with irinotecan and by 50% more with vincristine compared with nontransfected CHO cells. Melphalan produced 20% to 30% more inhibition in hOCT3-expressing cells compared with nonexpressing control cells. Similar results were obtained for A498 and ACHN cells. Thus, our data support the hypothesis that the sensitivity of tumor cells to chemotherapeutic treatment depends on the expression of transporter proteins mediating specific drug accumulation into target cells.
For perioperative mechanical ventilation under general anesthesia, modern respirators aim at combining the benefits of pressure-controlled ventilation (PCV) and volume-controlled ventilation (VCV) in modes typically named “volume-guaranteed” or “volume-targeted” pressure-controlled ventilation (PCV-VG). This systematic review and meta-analysis tested the hypothesis that PCV-VG modes of ventilation could be beneficial in terms of improved airway pressures (Ppeak, Pplateau, Pmean), dynamic compliance (Cdyn), or arterial blood gases (PaO2, PaCO2) in adults undergoing elective surgery under general anesthesia. Three major medical electronic databases were searched with predefined search strategies and publications were systematically evaluated according to the Cochrane Review Methods. Continuous variables were tested for mean differences using the inverse variance method and 95% confidence intervals (CI) were calculated. Based on the assumption that intervention effects across studies were not identical, a random effects model was chosen. Assessment for heterogeneity was performed with the χ2 test and the I2 statistic. As primary endpoints, Ppeak, Pplateau, Pmean, Cdyn, PaO2, and PaCO2 were evaluated. Of the 725 publications identified, 17 finally met eligibility criteria, with a total of 929 patients recruited. Under supine two-lung ventilation, PCV-VG resulted in significantly reduced Ppeak (15 studies) and Pplateau (9 studies) as well as higher Cdyn (9 studies), compared with VCV [random effects models; Ppeak: CI −3.26 to −1.47; p < 0.001; I2 = 82%; Pplateau: −3.12 to −0.12; p = 0.03; I2 = 90%; Cdyn: CI 3.42 to 8.65; p < 0.001; I2 = 90%]. For one-lung ventilation (8 studies), PCV-VG allowed for significantly lower Ppeak and higher PaO2 compared with VCV. In Trendelenburg position (5 studies), this effect was significant for Ppeak only. This systematic review and meta-analysis demonstrates that volume-targeting, pressure-controlled ventilation modes may provide benefits with respect to the improved airway dynamics in two- and one-lung ventilation, and improved oxygenation in one-lung ventilation in adults undergoing elective surgery.
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