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MicroRNAs (miRNAs) are involved in the maintenance of the cancer stem cell (CSC) phenotype by binding to genes and proteins that modulate cell proliferation and/or cell apoptosis. In our study, we aimed to investigate the role of miR-1305 in the proliferation and self-renewal of liver CSCs (LCSCs) via the ubiquitin-conjugating enzyme E2T (UBE2T)-mediated Akt-signaling pathway. Differentially expressed genes in human hepatocellular carcinoma (HCC) were obtained by in silico analysis. The relationship between miR-1305 and UBE2T was verified by dual luciferase reporter gene assay. qRT-PCR and western blot analysis were performed to determine the expression of UBE2T, the Akt-signaling pathway, and stemness-related factors in LCSCs. In addition, miR-1305 disrupted the activation of the Akt-signaling pathway by targeting UBE2T, and, ultimately, it repressed the sphere formation, colony formation, and proliferation, as well as tumorigenicity of LCSCs. In summary, miR-1305 targeted UBE2T to inhibit the Akt-signaling pathway, thereby suppressing the self-renewal and tumorigenicity of LCSCs. Those findings may provide an enhanced understanding of miR-1305 as a therapeutic target to limit the progression of LCSCs.

This phase II study (ALTER-H006; NCT05111366) evaluates adjuvant benmelstobart plus anlotinib in patients with high-risk recurrence (including ≥4 tumors, portal vein tumor thrombus [Vp1/2], or hepatic vein tumor thrombus [Vv1/2]) after hepatocellular carcinoma (HCC) resection. Primary endpoint is 1-year recurrence-free survival (RFS) rate. Secondary endpoints include overall survival (OS), 1-year OS rate, RFS, and safety. Median follow-up is 12.6 months. Among 37 patients enrolled, 1-year RFS rate is 59.7%, and median RFS is 15.6 months. Subgroups with Vp1/2 and Vv1/2 show median RFS of 18.2 months and not reached (NR), respectively. The longest recurrence-free duration is 25.9 months. Median OS is NR (1-year OS rate, 91.7%). Grade ≥3 treatment-related adverse events occur in 45.9% of patients, most commonly hypertension. No treatment-related deaths occur. Here, we show that adjuvant benmelstobart plus anlotinib is a feasible treatment option for HCC patients with high-risk recurrence after HCC resection, warranting confirmation in large-scale randomized clinical trials. Effective therapies remain limited for patients with high-risk recurrence after hepatocellular carcinoma (HCC) resection. Here, the authors report a clinical trial investigating the adjuvant combination of the anti-PD-L1 antibody benmelstobart plus the multi-targeted tyrosine kinase inhibitor anlotinib, in patients with high-risk recurrence after resection of HCC.

Portal vein tumor thrombus (PVTT) is very common and it plays a major role in the prognosis and clinical staging of hepatocellular carcinoma (HCC). We have published the first version of the guideline in 2016 and revised in 2018. Over the past several years, many new evidences for the treatment of PVTT become available, especially for the advent of new targeted drugs and immune checkpoint inhibitors which have further improved the prognosis of PVTT. So, the Chinese Association of Liver Cancer and Chinese Medical Doctor Association revised the 2018 version of the guideline to adapt to the development of PVTT treatment. Future treatment strategies for HCC with PVTT in China would depend on new evidences from more future clinical trials.

It has been shown that aberrant expression of microRNAs (miRNAs) and transcriptional factors (TFs) is tightly associated with the development of HCC. Therefore, in order to further understand the pathogenesis of HCC, it is necessary to systematically study the relationship between the expression of miRNAs, TF and genes. In this study, we aim to identify the potential transcriptomic markers of HCC through analyzing common microarray datasets, and further establish the differential co-expression network of miRNAs-TF-mRNA to screen for key miRNAs as candidate diagnostic markers for HCC. We first downloaded the mRNA and miRNA expression profiles of liver cancer from the GEO database. After pretreatment, we used a linear model to screen for differentially expressed genes (DEGs) and miRNAs. Further, we used weighed gene co-expression network analysis (WGCNA) to construct the differential gene co-expression network for these DEGs. Next, we identified mRNA modules significantly related to tumorigenesis in this network, and evaluated the relationship between mRNAs and TFs by TFBtools. Finally, the key miRNA was screened out in the mRNA-TF-miRNA ternary network constructed based on the target TF of differentially expressed miRNAs, and was further verified with external data set. A total of 465 DEGs and 215 differentially expressed miRNAs were identified through differential genes expression analysis, and WGCNA was used to establish a co-expression network of DEGs. One module that closely related to tumorigenesis was obtained, including 33 genes. Next, a ternary network was constructed by selecting 256 pairs of mRNA-TF pairs and 100 pairs of miRNA-TF pairs. Network mining revealed that there were significant interactions between 18 mRNAs and 25 miRNAs. Finally, we used another independent data set to verify that miRNA hsa-mir-106b and hsa-mir-195 are good classifiers of HCC and might play key roles in the progression of HCC. Our data indicated that two miRNAs-hsa-mir-106b and hsa-mir-195-are identified as good classifiers of HCC.

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. Most HCC patients are first diagnosed at an advanced stage, and systemic treatments are the mainstay of treatment. Summary: In recent years, immune checkpoint inhibitors have made a breakthrough in the systemic treatment of middle-advanced HCC, breaking the single therapeutic pattern of molecular-targeted agents. To better guide the clinical treatment for effective and safe use of immunotherapeutic drugs, the Chinese Association of Liver Cancer and Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the “Chinese Clinical Expert Consensus on Immunotherapy for Hepatocellular Carcinoma (2021)” based on current clinical studies and clinical medication experience for reference in China. Key Messages: The consensus contained 17 recommendations, including the preferred regimen for first- and second-line immunotherapy, evaluation and monitoring before/during/after treatment, management of complications, precautions for special patients, and potential population for immunotherapy.

There is no guideline recommendation for preventing hepatocellular carcinoma (HCC) recurrence after hepatic resection. Moreover, an unmet need exists on the effectiveness of sorafenib therapy in recurrent HCC. We therefore assessed the efficacy and safety of sorafenib in Chinese HCC patients with high risk of recurrence. Data were collected retrospectively from 15 Chinese research centers from January 1, 2012 to November 15, 2013, by chart reviews of patients with moderate-advanced HCC who received hepatic carcinectomy. The primary end point was recurrence-free survival rate at 1 year in patients with a high recurrence risk. Secondary end points included 1-year survival rate, time to recurrence and safety assessment. A total of 209 high-risk patients (sorafenib, n=98; control, n=111) who underwent carcinectomy were analyzed. There was no significant difference in the proportion of patients with recurrence-free survival at 1 year between the sorafenib and control (70.43% vs 68.90%: χ =0.007, =0.934). One-year survival rate was significantly higher with sorafenib than observed with control (95.5% vs 83.35%; χ =7.441, =0.006). Time to recurrence between sorafenib and control groups was similar. Incidences of all the adverse events (AEs) were similar in both the groups and transaminase elevation was most common in both groups (20.37% vs 24.79%). Thrombocytopenia incidence was significantly lower with the sorafenib group than with control (1.85% vs 9.40%; =0.015). Sorafenib may be considered as a feasible option in the treatment of HCC recurrence.

MicroRNA-21 (miR-21) is a potential therapeutic target for melanoma. Whether miR-21 inhibitor affects the anti-cancer activity of doxorubicin assisted by c(RGDyK)-modified liposome (DLN) in melanoma and the underlying mechanisms are largely unknown. In this study, in vitro and animal models were used to explore the effect of DLN combined with miR-21 inhibitor on melanoma cells. The data demonstrated that treatment with 5 µl DLN (final concentration of doxorubicin 5 mg/ml) for 72 h effectively inhibited melanoma cell growth (~75% inhibition). The experiments were then divided into five groups: Control group, vector group, DLN group, miR-21 inhibitor group and miR-21 inhibitor + DLN group. Compared with the control group, DLN (5 µl) or miR-21 inhibitor significantly reduced migration and invasion of melanoma cells, promoted apoptosis and arrested cells at the G1 phase. Notably, the combined application of DLN with miR-21 inhibitor further promoted the anti-cancer effects (reducing migration and invasion of melanoma cells, promoting apoptosis and arresting cells at G1 phase) compared with individual application of DLN or miR-21 inhibitor. Mechanically, DLN did not function by reducing miR-21 expression, whereas DLN and miR-21 inhibitor downregulated B-cell lymphoma-2 (BCL-2) expression, and facilitated BCL-2-associated X protein (Bax) and P53 expression in melanoma cells. DLN and miR-21 inhibitor together displayed stronger effects on Bcl-2, Bax and P53 expression that each alone. In vivo data further demonstrated that DLN inhibited tumor growth further than a similar dose of doxorubicin only. Furthermore, miR-21 inhibitor and DLN exerted the optimal anti-cancer effect compared with single application of DLN or miR-21 inhibitor. Together, the findings demonstrated miR-21 inhibitor facilitated the anti-cancer activity of DLN in melanoma, and the mechanisms involved Bcl-2, Bax and P53 expression.