Introduction: This retrospective study aimed to compare the efficacy and safety of transarterial chemoembolization plus lenvatinib and programmed death 1 (PD-1) inhibitors versus transarterial chemoembolization plus lenvatinib or sorafenib in patients with unresectable hepatocellular carcinoma. Methods: Consecutive patients with unresectable hepatocellular carcinoma who received transarterial chemoembolization plus lenvatinib and PD-1 inhibitors, lenvatinib, or sorafenib were retrospectively identified in our institution between January 2018 and August 2020. The primary endpoint was overall survival. Results: A total of 84 patients were included in this analysis. The median overall survival was significantly improved in the transarterial chemoembolization plus lenvatinib and PD-1 inhibitor group compared with the transarterial chemoembolization plus sorafenib group (26.7 months [95% confidence interval 25.2-31.6] vs 14.4 months [95% confidence interval 9.5-18.9]; hazard ratio 0.39 [95% confidence interval 0.17-0.72]; P  =  .007) or the transarterial chemoembolization plus lenvatinib group (26.7 months [95% confidence interval 25.2-31.6] vs 17.9 [95% confidence interval 13.4-22.2] months; hazard ratio 0.45 [95% confidence interval 0.17-0.87]; P  =  .031). Transarterial chemoembolization plus lenvatinib and PD-1 inhibitor also significantly prolonged median progression-free survival compared with transarterial chemoembolization plus sorafenib group (8.2 months [95% confidence interval 3.3-13.0] vs 6.0 months [95% confidence interval 4.2-7.8]; hazard ratio 0.47 [95% confidence interval 0.24-0.74]; P  =  .005) or the transarterial chemoembolization plus lenvatinib group (8.2 months [95% confidence interval 3.3-13.0] vs 6.6 [95% confidence interval 4.3-7.9] months; hazard ratio 0.58 [95% confidence interval 0.31-0.96]; P  =  .047). No significant difference was seen between groups in the incidence of an adverse event or grade 3 or higher adverse event. Conclusion: Transarterial chemoembolization plus lenvatinib, and PD-1 inhibitor was associated with better survival benefits and acceptable toxicities, which may provide an additional therapeutic option for unresectable hepatocellular carcinoma.

Background: Long noncoding RNAs have been known to be involved in various cancers. This study aimed to find a long noncoding RNA signature to predict the prognostic risk of patients with digestive cancers, including esophageal carcinoma, stomach adenocarcinoma, liver hepatocellular carcinoma, and pancreatic adenocarcinoma. Methods: After screening differentially expressed long noncoding RNAs in 4 digestive cancers from The Cancer Genome Atlas database, the prognostic significance of the above differentially expressed long noncoding RNAs was evaluated by Kaplan–Meier analysis. Target genes of the corresponding differentially expressed long noncoding RNAs were predicted by StarBase. We performed bioinformatics methods, including gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, to explore the role and molecular mechanisms of differentially expressed long noncoding RNAs and predicted target genes in tumor progression. Results: A total of 4 differentially expressed long noncoding RNAs (AC093895.1, CASC9, LINC01980, and HOXC-AS2) with a significant prognostic value were identified. Moreover, 6 target genes were obtained. Also, functional enrichment analysis showed that these 4 DELs were mainly related to the regulation of mRNA metabolic process, regulation of RNA stability, mRNA binding, RNA localization, and spliceosome. Conclusion: The prognostic differentially expressed long noncoding RNAs and target genes in the digestive cancers were obtained, which may provide a novel direction for treatment and prognosis improvement of digestive cancers.

Background: Anlotinib, a multitargeted tyrosine kinase inhibitor, has been shown to have encouraging activity against many tumors, but its cardiovascular toxicity has not been investigated specifically. We reviewed anlotinib-associated cardiovascular adverse events in patients and explored its cardiotoxicity in vitro. Methods: We retrospectively reviewed all cardiovascular events in 62 patients with unresectable tumors who had taken anlotinib and mainly examined anlotinib’s effects on left ventricular ejection fraction (LVEF) and blood pressure. Besides, we investigated its cardiotoxicity in Neonatal Rat Ventricular Myocytes (NRVMs). Results: All-grade hypertension was seen in 60 patients (97%), and 25 individuals (40%) developed grade 3 hypertension. Significant univariate associations for predictors of post-treatment hypertension were age ( P<0.001), BMI ( P=0.003), ECOG PS( P<0.001), diabetes mellitus ( P=0.035), dose of anlotinib ( P=0.025). Multivariate analysis suggested that age [odds ratio (OR) 1.079, 95% confidence interval (CI): 1.029–1.130, P= 0.001] and BMI [OR 3.448, 95% CI: 1.410–8.433, P= 0.007] were the only significant independent predictors. No grade 3/4 left ventricular systolic dysfunction was reported. One patient (2%) had acute myocardial infarction, leading to cardiac death. In vitro, western blotting results showed that the levels of ANP, BNP, c-Myc and Cleaved Caspase3 were notably increased and cardiomyocyte apoptosis was strikingly increased in anlotinib group, as detected by TUNEL staining and Annexin V-FITC/PI flow cytometry. Conclusions: Our study results showed that anlotinib could induce rat cardiomyocytes apoptosis. Nonetheless, anlotinib-associated cardiovascular toxicity was acceptable and manageable for patients with unresectable tumors.