Malignant pleural effusion (MPE) is a common complication of advanced non-small cell lung cancer (NSCLC). Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), has been shown to be efficient in suppressing the accumulation of pleural fluid. However, whether intrapleural delivery of bevacizumab can be used to treat MPE remains unknown. The aim of the present study was to evaluate the efficacy and safety of combined intrapleural therapy with bevacizumab and cisplatin, an antineoplastic agent, in controlling MPE. A total of 72 NSCLC study subjects with MPE were randomly assigned to one of two groups. The first group received intrapleural bevacizumab (300 mg) with cisplatin (30 mg) therapy and the second group received intrapleural cisplatin (30 mg) therapy alone. Pleural fluid was collected from both groups prior to and following treatment. The levels of VEGF and carcinoembryonic antigen (CEA) in the pleural fluid were determined by ELISA. In 70 evaluable study subjects, the curative efficacy in the bevacizumab group was significantly higher than that found in the cisplatin group (83.33 vs. 50.00%, respectively; p<0.05). Therapy with combined bevacizumab plus cisplatin significantly reduced VEGF levels in the pleural fluid (p<0.01). In the bevacizumab group, the levels of VEGF in the pleural fluid were significantly lower compared to those of the cisplatin group after treatment, which showed greater efficacy (p<0.01). In addition, combination therapy showed greater efficacy in the patients with high levels of VEGF expression (p<0.01). There was no significant difference in grade III/IV adverse events between the two groups. All procedures were well tolerated by the patients. Combined intrapleural therapy with bevacizumab and cisplatin was effective and safe in managing NSCLC-mediated MPE. We propose that VEGF expression levels in MPE could serve as a prognostic marker for bevacizumab therapy.

Background and Aims Oxaliplatin (OXA) is one of the most common chemotherapeutics in advanced hepatocellular carcinoma (HCC), the resistance of which poses a big challenge. Long noncoding RNAs (lncRNAs) play vital roles in chemoresistance. Therefore, elucidating the underlying mechanisms and identifying predictive lncRNAs for OXA resistance is needed urgently. Methods RNA sequencing (RNA‐seq) and fluorescence in situ hybridization (FISH) were used to investigate the OXA‐resistant (OXA‐R) lncRNAs. Survival analysis was performed to determine the clinical significance of homo sapiens long intergenic non‐protein‐coding RNA 1134 (LINC01134) and p62 expression. Luciferase, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and chromatin isolation by RNA purification (ChIRP) assays were used to explore the mechanisms by which LINC01134 regulates p62 expression. The effects of LINC01134/SP1/p62 axis on OXA resistance were evaluated using cell viability, apoptosis, and mitochondrial function and morphology analysis. Xenografts were used to estimate the in vivo regulation of OXA resistance by LINC01134/SP1/p62 axis. ChIP, cell viability, and xenograft assays were used to identify the demethylase for LINC01134 up‐regulation in OXA resistance. Results LINC01134 was identified as one of the most up‐regulated lncRNAs in OXA‐R cells. Higher LINC01134 expression predicted poorer OXA therapeutic efficacy. LINC01134 activates anti‐oxidative pathway through p62 by recruiting transcription factor SP1 to the p62 promoter. The LINC01134/SP1/p62 axis regulates OXA resistance by altering cell viability, apoptosis, and mitochondrial homeostasis both in vitro and in vivo. Furthermore, the demethylase, lysine specific demethylase 1 (LSD1) was responsible for LINC01134 up‐regulation in OXA‐R cells. In patients with HCC, LINC01134 expression was positively correlated with p62 and LSD1 expressions, whereas SP1 expression positively correlated with p62 expression. Conclusions LSD1/LINC01134/SP1/p62 axis is critical for OXA resistance in HCC. Evaluating LINC01134 expression in HCC will be effective in predicting OXA efficacy. In treatment‐naive patients, targeting the LINC01134/SP1/p62 axis may be a promising strategy to overcome OXA chemoresistance.

Risk of metastasis is increased by the presence of chromosome 3 monosomy in uveal melanoma (UM). This study aimed to identify more accurate biomarker for risk of metastasis in UM. A total of 80 patients with UM from TCGA were assigned to two groups based on the metastatic status, and bioinformatic analyses were performed to search for critical genes for risk of metastasis. SLC25A38, located on chromosome 3, was the dominant downregulated gene in metastatic UM patients. Low expression of SLC25A38 was an independent predictive and prognostic factor in UM. The predictive potential of SLC25A38 expression was superior to that of pervious reported biomarkers in both TCGA cohort and GSE22138 cohort. Subsequently, its role in promoting metastasis was explored in vitro and in vivo. Knock-out of SLC25A38 could enhance the migration ability of UM cells, and promote distant metastasis in mice models. Through the inhibition of CBP/HIF-mediated pathway followed by the suppression of pro-angiogenic factors, SLC25A38 was situated upstream of metastasis-related pathways, especially angiogenesis. Low expression of SLC25A38 promotes angiogenesis and metastasis, and identifies increased metastatic risk and worse survival in UM patients. This finding may further improve the accuracy of prognostic prediction for UM.