Elderly patients are at increased risk for significant DDIs when treated with DAAs for chronic HCV infection. However, with careful pre-treatment assessment of concomitant medications, on-treatment monitoring or dose-modifications, significant DDIs and associated adverse events can be avoided.
BackgroundOrganic cation transporters (OCT) are responsible for the uptake and intracellular inactivation of a broad spectrum of endogenous substrates and detoxification of xenobiotics and chemotherapeutics. The transporters became pharmaceutically interesting, because OCTs are determinants of the cytotoxicity of platin derivates and the transport activity has been shown to correlate with the sensitivity of tumors towards tyrosine kinase inhibitors. No data exist about the relevance of OCTs in hepatocellular carcinoma (HCC).MethodsOCT1 (SLC22A1) and OCT3 (SLC22A3) mRNA expression was measured in primary human HCC and corresponding non neoplastic tumor surrounding tissue (TST) by real time PCR (n = 53). Protein expression was determined by western blot analysis and immunofluorescence. Data were correlated with the clinicopathological parameters of HCCs.ResultsReal time PCR showed a downregulation of SLC22A1 and SLC22A3 in HCC compared to TST (p ≤ 0.001). A low SLC22A1 expression was associated with a worse patient survival (p < 0.05). Downregulation was significantly associated with advanced HCC stages, indicated by a higher number of T3 tumors (p = 0.025) with a larger tumor diameter (p = 0.035), a worse differentiation (p = 0.001) and higher AFP-levels (p = 0.019). In accordance, SLC22A1 was less frequently downregulated in tumors with lower stages who underwent transarterial chemoembolization (p < 0.001) and liver transplantation (p = 0.001). Tumors with a low SLC22A1 expression (< median) showed a higher SLC22A3 expression compared to HCC with high SLC22A1 expression (p < 0.001). However, there was no significant difference in tumor characteristics according to the level of the SLC22A3 expression.In the western blot analysis we found a different protein expression pattern in tumor samples with a more diffuse staining in the immunofluorescence suggesting that especially OCT1 is not functional in advanced HCC.ConclusionThe downregulation of OCT1 is associated with tumor progression and a worse patient survival.
Background/Aims: The use of intraoperative blood salvage autotransfusion (IBSA) during surgical approaches may contribute to tumour cell dissemination. Therefore, IBSA should be avoided in cases of malignancy. However, the risks of IBSA might be acceptable in liver transplantation (LT) for selected small hepatocellular carcinoma (HCC). Methods: In total, 136 recipients of LT with histologically proven HCC in the explanted liver were included in this analysis. With regard to tumour recurrence, 40 patients receiving IBSA despite HCC (IBSA group) were compared to 96 patients without IBSA (non-IBSA group). Results: Milan criteria as assessed in the explanted liver were fulfilled in 24 of 40 IBSA patients and 58 of 96 non-IBSA patients (p = 0.85). Five of 40 patients in the IBSA group and 18 of 96 patients in the non-IBSA group experienced tumour recurrence (p = 0.29). In spite the theoretical risk of tumour cell dissemination, the recurrence rate was not increased in the IBSA group. Conclusion: Our results indicate that IBSA does not modify the risk of HCC recurrence. Therefore, in highly selected HCC patients undergoing LT, the use of IBSA appears to be justified.
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