Although the use of sorafenib appears to increase the survival rate of renal cell carcinoma (RCC) patients, there is also a proportion of patients who exhibit a poor primary response to sorafenib therapy. It is therefore critical to elucidate the mechanisms underlying sorafenib resistance and find representative biomarkers for sorafenib treatment in RCC patients. Herein, we identified a long non-coding RNA referred to as lncRNA-SRLR (sorafenib resistance-associated lncRNA in RCC) that is upregulated in intrinsically sorafenib-resistant RCCs. lncRNA-SRLR knockdown sensitized nonresponsive RCC cells to sorafenib treatment, whereas the overexpression of lncRNA-SRLR conferred sorafenib resistance to responsive RCC cells. Mechanistically, lncRNA-SRLR directly binds to NF-κB and promotes IL-6 transcription, leading to the activation of STAT3 and the development of sorafenib tolerance. A STAT3 inhibitor and IL-6-receptor antagonist both restored the response to sorafenib treatment. Moreover, a clinical investigation demonstrated that high levels of lncRNA-SRLR correlated with poor responses to sorafenib therapy in RCC patients. Collectively, lncRNA-SRLR may serve as not only a predictive biomarker for inherent sorafenib resistance but also as a therapeutic target to enhance responses to sorafenib in RCC patients.
Background The aim of this study was to evaluate and compare three nutritional screening tools with the new GLIM criteria for malnutrition among definitive and elective surgery Crohn’s patients in China. Methods Nutritional screening tools, including the nutritional screening tool for IBD (NS-IBD), the Nutritional Risk Screening 2002 (NRS 2002), the Prognostic Nutrition Index (PNI) were applied to 212 patients with definitive and elective surgery Crohn’s patients in China. We compared the diagnostic values of these tools for malnutrition, using the new GLIM criteria for malnutrition as the ‘gold standards’. Results According to the new GLIM criteria for malnutrition, 81(61.79%) of the patients were diagnosed as malnutrition. With the use of NRS-2002, 140(66.10%)of the patients were found to be at high risk of malnutrition; with the use of NS-IBD, 181(85.30% )of the patients were found to be at moderate/high risk of malnutrition; and according to PNI, 94(44.0%)of the patients were found to be at moderate/high nutritional risk. The comparison of each nutritional risk tool showed sensitivity of 83.26%,85.74%,79.83%, and specificity was 62.91%,54.62%,57.34% for NRS-2002, NS-IBD and PNI, respectively. NS-IBD was best correlated with the ESPEN diagnostic criteria (К=0.388, p<0.001) compared with PNI (К=0.208, p=0.007) and NRS-2002 (К=0.744, p<0.032).The receiver operating characteristic curve of PNI had the highest area under the curve (AUC) compared with NRS 2002 and NS-IBD. Conclusion In the future, the combined application of GLIM criteria and two nutritional screening tools can better reflect the nutritional status for definitive and elective surgery Crohn’s patients.
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