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The radiation-induced inflammatory response is involved in radiation damage to the cochlea and causes sensorineural hearing loss (SNHL). NF-κB, as the master switch of the inflammatory response, regulates the expression of many inflammation-related genes and thus the inflammatory response. Therefore, in this study we used a mouse model to determine whether radiation-induced NF-κB activation is involved in damage to the cochlea and to investigate the underlying mechanism. Eventually, we found that NF-κB was activated after radiation of the cochleae and the activation reached a maximum at 2–6 h after radiation. And morphological analysis showed severe damage to the cochleae after radiation, but this damage was significantly ameliorated by JSH-23 (an inhibitor of NF-κB) pretreatment. Along with these morphological changes, the expression levels of proinflammatory molecules (including proinflammatory cytokines IL-6, TNF-α, COX-2 and inflammation-related proteins VCAM-1, MIP-1β) in the cochlear tissues were significantly increased after radiation, but were significantly decreased by JSH-23 pretreatment compared to radiation alone. Therefore, these results indicated that radiation-induced NF-κB activation was involved in damage to the cochleae and resultant SNHL via its promotion of the inflammatory response mediated by overexpression of some proinflammatory molecules in cochlear tissues, and inhibition of radiation-induced NF-κB was conducive to preventing such damage. [ABSTRACT FROM AUTHOR]

Because of the high heterogeneity of breast cancer outcome, identification of novel prognostic biomarkers is critical to improve patient stratification and guide precise treatment. We examined the prognostic value of gamma‐interferon‐inducible lysosomal thiol reductase (GILT) expression in a training set of 416 breast cancer patients and a validation set of 210 patients, and performed functional studies to investigate the functions and underlying mechanisms of GILT on breast cancer prognosis. Our results indicated that high GILT expression in breast cancer cells was associated with improved disease‐free survival (DFS; hazard ratio [HR] = 0.189, 95% confidence interval [CI]: 0.099‐0.361) and breast cancer‐specific survival (BCSS; HR = 0.187, 95% CI: 0.080‐0.437) of breast cancer patients both in the training set and the external validation set (HR = 0.453, 95% CI: 0.235‐0.873 for DFS, HR = 0.488, 95% CI: 0.245‐0.970 for BCSS). In vitro and in vivo studies showed that GILT overexpression inhibited breast cancer cells proliferation, invasion, migration and tumor formation in nude mice and increased sensitivity of breast cancer cells to standard treatment. Proteomics analysis indicated that GILT inhibited reactive oxygen species (ROS) and autophagy activation in breast cancer cells, and GILT overexpression‐mediated tumor growth was further enhanced in the presence of autophagy or ROS inhibitors. Our results demonstrate that GILT expression can be effectively used to predict the prognosis and guide treatment strategies of breast cancer patients. What's new? Because of the complexity and heterogeneity of breast tumours, the current prognostic markers have a limited prediction power. This retrospective observational study showed that high expression of the reductase GILT was associated with improved outcomes in a training set of 416 breast cancer patients and an independent validation set of 210 patients. GILT overexpression inhibited breast cancer cell proliferation, motility, and tumour formation in nude mice and increased breast cancer cell sensitivity to treatment by suppressing reactive oxygen species and autophagy. The results identified GILT as a novel prognostic biomarker that can effectively predict the prognosis of breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: A tendency towards extensive regional lymph node metastasis (LNM) is a typical clinical characteristic of esophageal squamous cell carcinoma (ESCC). Up-regulated microRNA (miR)-19a-3p was verified as a predictor of LNM in ESCC in previous microarray analyses, but the underlying mechanisms remain unclear. Here, in vitro experiments were performed to confirm the effect of miR-19a-3p on promoting LNM and to explore the underlying mechanisms., Methods: KYSE-150 and TE-1 cell lines were transfected with lentiviral vectors to inhibit miR-19a-3p (LV-miR-19a-3p-inhibition), and cell proliferation, invasion, and migration were assessed. Target genes of miR-19a-3p were identified by sequencing analysis and quantitative reverse transcription PCR (qRT-PCR); Western blotting was performed to confirm targets and explore the potential mechanisms underlying the effect of miR-19a-3p on LNM., Results: miR-19a-3p had no effect on ESCC cell proliferation, whereas miR-19a-3p overexpression promoted the invasion and migration of ESCC cells. qRT-PCR verification and western blot analysis showed that LV-miR-19a-3p-inhibition downregulated cell division cycle 42 (CDC42), Rac family small GTPase 1 (RAC1), and p21 activated kinase 1 (PAK1)., Conclusions: Overexpression of miR-19a-3p increased the invasion and migration of ESCC cells via the RAC1/CDC42-PAK1 pathway, suggesting that this pathway mediates the effect of miR-19a-3p on promoting LNM in ESCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tcr-21-254). The authors have no conflicts of interest to declare., (2021 Translational Cancer Research. All rights reserved.)

MicroRNAs (miRNAs) have attracted many attentions in lymphoma diagnostic research. The inconsistence of diagnostic performance in these existed literatures leading us to conduct this meta-analysis. In order to have a scientific and reliable study, all related articles were screened from Medline, Embase, CNKI and other databases. The sensitivity and specificity of each involved research were used to plot the summary receiver operator characteristic (SROC) curve and calculate the area under the curve (AUC). The QUADAS-2 tool was applied to estimate the quality of included studies. In addition, Deeks' funnel plot asymmetry test was performed to estimate publication bias. Overall, 14 studies from 6 articles were included to evaluate the whole test performance. The overall pooled results were as follows: sensitivity was 0.91 (95% CI: 0.83-0.95), specificity was 0.84 (95% CI: 0.75-0.90), the AUC was 0.93 (95% CI: 0.91-0.95), positive likelihood ratio-PLR was 5.5 (95% CI: 3.5-8.8), negative likelihood ratio-NLR was 0.11 (95% CI: 0.06-0.21), and diagnostic odds ratio-DOR was 50 (95% CI: 19-128). In summary, results from meta-analysis showed that miRNAs analysis might significantly increase the diagnostic accuracy of lymphoma. Further massive prospective studies still needed to validate our conclusion before clinical application.

Background: Erythropoiesis-stimulating agents (ESAs) are widely used in the management of anemia in cancer patients. Despite their apparent effectiveness, recent studies have suggested that ESAs could result in serious adverse events and even higher mortality. The aim of the current study was to evaluate the benefits and risks of ESAs in the management of cancer patients with anemia using a meta-analysis., Methods: The initial literature search covered Medline, PubMed, Embase, and the Cochrane Center Register of Controlled Trials, and identified 1,569 articles. The final meta-analysis included eight randomized controlled trials (n=2,387) in cancer patients with <11 g/dL hemoglobin (Hb) at the baseline and target Hb (for stopping ESA treatment) at no more than 13 g/dL. The assessment measures included Hb response, blood transfusion rate and adverse events that included venous thromboemblism (VTE), hypertension, and on-study mortality. The results are expressed as pooled odds ratio (OR). Publication bias was assessed using funnel plot analysis., Results: ESAs significantly increased the Hb concentration [OR 7.85, 95% confidence interval (CI): 5.85 to 10.53, P<0.001] and reduced the red blood cell (RBC) transfusion rate (OR 0.52, 95% CI: 0.42 to 0.65, P<0.001). ESAs did not increase the accumulated adverse events (OR 0.95, P=0.82), or the on-study mortality (OR 1.09, P=0.47)., Conclusions: ESAs are not associated with increased frequency of severe adverse events in anemic cancer patients when the target Hb value is no more than 13 g/dL.