Transarterial chemoembolization with molecular targeted therapies plus camrelizumab for recurrent hepatocellular carcinoma.

BACKGROUND: The safety and efficacy of transarterial chemoembolization plus molecular targeted therapy (MTT) combined with immune checkpoint inhibitors (ICIs) in primary liver cancer have been demonstrated. However, the evidence for TACE plus MTT combined with ICIs in the treatment of recurrent hepatocellular carcinoma (RHCC) is limited. Given the excellent performance of this combination regimen in primary liver cancer, it is necessary to evaluate the efficacy of TACE plus MTT combined with ICIs in RHCC. METHODS: A total of 88 patients with RHCC treated with TACE plus MTT combined with camrelizumab (TACE-TC group, n = 46) or TACE plus MTT (TACE-T group, n = 42) were retrospectively collected and analyzed. In this study, we evaluated the effectiveness and safety of combination therapy for patients with RHCC by analyzing tumor response, progression-free survival (PFS), overall survival (OS), laboratory biochemical indices, and adverse events (AEs). RESULTS: TACE-TC was superior to TACE-T in PFS (14.0 vs. 8.9 months, p = 0.034) and OS (31.1 vs. 20.2 months, p = 0.009). Moreover, TACE-TC achieved more preferable benefits with respect to disease control rate (89.1% vs. 71.4%, p = 0.036) and objective response rate (47.8% vs. 26.2%, p = 0.036) compared with TACE-T in patients with RHCC. Compared with the TACE-T group, the AFP level in the TACE-TC group decreased more significantly after 3 months of treatment. Multivariate analysis showed that treatment option was a significant predictor of OS and PFS, while the portal vein tumor thrombus and interval of recurrence from initial treatment were another prognostic factor of PFS. There was no significant difference between the TACE-TC and TACE-T groups for Grade 3-4 adverse events. CONCLUSIONS: A combination therapy of TACE, MTT, and camrelizumab significantly improved tumor response and prolonged survival duration, showing a better survival prognosis for RHCC patients.

AFAP1-AS1/Hsa-miR-15a-5p/Bcl-2 Axis is a Potential Regulator of Cancer Cell Proliferation and Apoptosis in Gallbladder Carcinoma.

OBJECTIVE: Gallbladder carcinoma (GBC) is a common malignancy of the biliary tract that, with late diagnosis, is often fatal. A better understanding of the underlying molecular mechanisms may facilitate targeted therapy for GBC. Therefore, this study aimed to investigate whether long non-coding RNA AFAP1-AS1 regulates GBC cell proliferation and apoptosis through hsa-miR-15a-5p. METHODS: SGC-996 and NOZ cell lines were transfected with an hsa-mR-15a-5p inhibitor or si-AFAP1-AS1, and GBC cell proliferation and apoptosis were measured. The expression levels of AFAP1-AS1, hsa-miR-15a-5p, apoptosis-related proteins, and bcl-2 were assessed. The dual-luciferase reporter assay was used to determine the binding between AFAP1-AS1 and hsa-miR-15a-5p or between hsa-miR-15a-5p and bcl-1. RESULTS: In SGC-996 and NOZ cells, AFAP1-AS1 was significantly expressed and hsa-miR-15a-5p was modestly expressed. Transfection of the hsa-miR-15a-5p inhibitor elevated proliferation of SGC-996 and NOZ cells and decreased apoptosis, whereas transfection of si-AFAP1-AS1 reduced the proliferation rate and increased apoptosis. In addition, AFAP1-AS1 bound hsa-miR-15a-5p and hsa-miR-15a-5p targeted bcl-2. Increased bcl-2 expression was observed in the GBC cells. AFAP1-AS1 may regulate GBC cell proliferation and apoptosis via has-miR-15a-5p to mediate bcl-2 expression. CONCLUSION: The AFAP1-AS1/hsa-miR-15a-5p/bcl-2 axis regulates GBC cell proliferation and apoptosis, providing potential guidance for the clinical treatment of GBC.

A Simple Prognostic Scoring System for Hepatocellular Carcinoma Treated with DEB-TACE.

Objective: To develop a simple and effective prognostic scoring system to predict the efficacy of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) in the treatment of hepatocellular carcinoma (HCC). Methods: Data were retrospectively collected from 230 patients with HCC who received DEB-TACE treatment at six medical centers between January 2019 and December 2022. We developed a predictive score based on independent risk factors for overall survival (OS), validated the model using a validation cohort, and compared its prognostic accuracy with commonly used HCC staging systems. Results: The number of tumors, albumin-bilirubin levels, alpha-fetoprotein levels, and portal vein thrombus grade were identified as independent factors influencing OS. Based on these factors, we established the DEB-TACE treatment of HCC (DTH) scoring system. The DTH score correlated well with OS, which decreased as the DTH score increased. According to the DTH score, patients were categorized into three risk groups: low-risk (DTH-A, 0-4 points), medium-risk (DTH-B, 5-6 points), and high-risk (DTH-A, 7 points). The OS of each risk group was 18.73±0.62 months, 12.73±0.10 months, and 6.93±0.19 months, respectively (p<0.001). The external cohort validation confirmed the accuracy of the DTH score, demonstrating superior predictive performance compared to other commonly used HCC scoring systems. Conclusion: The DTH-HCC scoring system effectively predicts the outcomes of HCC patients undergoing DEB-TACE as initial treatment. This model can aid in the initial planning and decision-making process for DEB-TACE treatment in HCC patients.

Comparing the effectiveness and safety of Sorafenib plus TACE with Apatinib plus TACE for treating patients with unresectable hepatocellular carcinoma: a multicentre propensity score matching study.

OBJECTIVE: Local combined systemic therapy has been an important method for the treatment of unresectable hepatocellular carcinoma (HCC).The purpose of this study was to compare the effectiveness and safety of transarterial chemoembolization (TACE) plus Sorafenib versus TACE plus Apatinib for treating patients with unresectable HCC. METHODS: The clinical data of patients with unresectable HCC who were treated with TACE plus Sorafenib or TACE plus Apatinib at 5 Chinese medical centers between January 2016 and December 2020 were retrospectively analyzed. Propensity score matching (PSM) was applied to reduce the bias from confounding factors. RESULTS: A total of 380 patients were enrolled, of whom 129 cases were treated with TACE plus Sorafenib and 251 cases with TACE plus Apatinib. After the 1:1 PSM, 116 pairs of patients were involved in this study. The results showed that the PFS and OS in the TACE-Sorafenib group were significantly longer than those in the TACE-Apatinib group (PFS: 16.79 ± 6.45 vs. 14.76 ± 6.98 months, P = 0.049; OS: 20.66 ± 6.98 vs. 17.69 ± 6.72 months, P = 0.013). However, the ORR in the TACE-Apatinib group was markedly higher than that in the TACE-Sorafenib group (70.69% vs. 56.03%, P = 0.021). There were more patients with adverse events (AEs) in the TACE-Apatinib group than those in the TACE-Sorafenib group before dose adjustment (87 vs. 63, P = 0.001); however, the number of patients who suffered from AEs was not significantly different between the two groups after the dose adjustment (62 vs. 55, P = 0.148). No treatment-related death was found in the two groups. Subgroup analysis revealed that patients with unresectable HCC could better benefit from regular doses than reduced doses (Sorafenib, 22.59 vs. 18.02, P < 0.001; Apatinib, 19.75 vs. 16.86, P = 0.005). CONCLUSION: TACE plus either Sorafenib or Apatinib could effectively treat patients with unresectable HCC, the safety of TACE plus Sorafenib was better. and the ORR of TACE plus Apatinib was higher.

The Efficacy and Prognostic Factors of the Combination of TACE and Apatinib for the Treatment of BCLC Stage C Hepatocellular Carcinoma.

Objective: Apatinib is a inhibitor of vascular endothelial growth factor receptor-2. To explore the efficacy and prognostic factors of transarterial chemoembolization (TACE) combined with apatinib in the treatment of Barcelona Clinic Liver Cancer stage C (BCLC C) hepatocellular carcinoma (HCC). Methods: Clinical data of 146 HCC patients with BCLC stage C admitted to our hospital were collected and analyzed retrospectively, of which 76 cases were treated with TACE combined with apatinib (TACE-apatinib) and 70 with TACE alone. The tumor response, survival time, and adverse events were compared between the two groups, and the factors affecting the prognosis were analyzed. Results: The objective response rate (ORR) and disease control rate (DCR) in the TACE-apatinib group were higher than in the TACE-alone group (ORR: 42.10 vs. 25.71%, P = 0.03; DCR: 84.21 vs. 55.71%, P = 0.001). The median time to progression (TTP) and overall survival (OS) in the TACE-apatinib group were longer than in the TACE-alone group (TTP: 5.5 vs. 3.7 months, P = 0.02; OS: 10.0 vs. 6.2 months, P = 0.01). Univariate and multivariate Cox regression analysis showed that tumor size, Child-Pugh class, and the presence of the portal vein tumor thrombus affect the prognosis of patients. Subgroup analysis revealed that TACE-apatinib therapy resulted in a higher OS in patients with tumor size <10 cm, without portal vein tumor thrombus, and with Child-Pugh class A (P < 0.05). The likelihood of adverse events (hand-foot syndrome, hypertension, oral ulcer) was significantly higher in the increased in the TACE-apatinib group than in the TACE alone group (P < 0.05). Conclusion: TACE-apatinib is an effective and safe method for the treatment of BCLC stage C HCC. Tumor size, Child-Pugh class, and portal vein tumor thrombus affect survival time in HCC patients with BCLC stage C.

Long non-coding RNA FAM133B-2 represses the radio-resistance of nasopharyngeal cancer cells by targeting miR-34a-5p/CDK6 axis.

Long non-coding RNAs (lncRNAs) were found to play roles in various cancers, including nasopharyngeal carcinoma. In this study, we focused on the biological function of the lncRNA FAM133B-2 in the radio-resistance of nasopharyngeal carcinoma. The RNA-seq and qRT-PCR analysis showed that FAM133B-2 is highly expressed in the radio-resistant nasopharyngeal carcinoma cells. The following biochemical assays showed that FAM133B-2 represses the nasopharyngeal carcinoma radio-resistance and also affects the apoptosis and proliferation of nasopharyngeal carcinoma cells. Further investigations suggested that miR-34a-5p targets FAM133B-2 and also regulates the cyclin-dependent kinase 6 (CDK6). All these results suggested that the lncRNA FAM133B-2 might function as a competitive endogenous RNA (ceRNA) for miR-34a-5p in nasopharyngeal carcinoma radio-resistance, thus it may be regarded as a novel prognostic biomarker and therapeutic target in nasopharyngeal carcinoma diagnosis and treatment.

Clinical evaluation of targeted arterial perfusion of verapamil and chemotherapeutic drugs in interventional therapy of advanced lung cancer.

PURPOSE: To assess the clinical efficacy of targeted arterial perfusion of verapamil and chemotherapeutic agents in the interventional therapy of lung cancer. METHODS: Forty patients with advanced lung cancer underwent treatment with targeted arterial perfusion of verapamil and chemotherapeutic agents using Seldinger technique. Interventional therapy was performed once a month, and each subject received interventional treatment for 2 or more cycles. The therapeutic efficacy was evaluated 2 months post-treatment. RESULTS: Out of 40 patients with advanced lung cancer, 5 cases achieved complete remission (CR) and 29 cases achieved partial remission (PR), with a total effectiveness (CR + PR) rate of 85 %. Besides, 32 cases achieved significantly alleviated clinical symptoms, and 29 cases had decreased clinical tumor stage. All subjects had stable karnofsky performance status score and body weight. Among the 40 patients, 13 cases had leucopenia, 10 cases had gastrointestinal reactions, 3 cases presented with elevated alanine aminotransferase/aspartate aminotransferase ratio, and 3 cases had fever. However, all these side effects relieved quickly. No elevation of BUN/Cr ratio and allergic reactions was observed. No significant changes in cardiac function and electrocardiogram were noticed after the treatment. CONCLUSIONS: Targeted arterial perfusion of verapamil and chemotherapeutic drugs can improve the clinical symptoms of patients with advanced lung cancer and increase the efficacy of chemotherapeutic agents, thereby providing an opportunity for radiotherapy or surgical treatment for advanced lung cancer.